Eur J Health Econ DOI 10.1007/s10198-014-0597-1
ORIGINAL PAPER
Subjective health expectations at biological therapy initiation: a survey of rheumatoid arthritis patients and rheumatologists Ma´rta Pe´ntek • La´szlo´ Gula´csi • Bernadette Rojkovich • Valentin Brodszky • Job van Exel • Werner B. F. Brouwer
Received: 7 February 2014 / Accepted: 31 March 2014 Springer-Verlag Berlin Heidelberg 2014
Abstract Subjective health expectations of patients with rheumatoid arthritis (RA) and rheumatologists remain understudied. We measured subjective expectations regarding treatment effects of biologicals as well as future length and quality of life. Moreover, we compared expectations regarding treatment effects to actual treatment effects. We recruited a sample of Hungarian RA patients initiating treatment with biologicals. Expectations regarding treatment effects and future health were obtained through a written questionnaire from patients and physicians, including functional impairment (HAQ-DI), health status (EQ-5D) and disease activity (DAS28). After three months, actual treatment effects were obtained. Ninety-two RA patients (females N = 81, 88 %) with mean age of 51 (SD 12) and disease duration of 9 (SD 8) years with high average disease activity (DAS28: 6.1) were included. Patients expected significant and large health improvement within three months with mean changes on the HAQ-DI of -0.8 and on the EQ-5D of ?0.4. M. Pe´ntek (&) L. Gula´csi V. Brodszky Department of Health Economics, Corvinus University of Budapest, F}ova´m te´r 8, Budapest 1093, Hungary e-mail: [email protected] M. Pe´ntek Department of Rheumatology, Flo´r Ferenc County Hospital, Semmelweis te´r 1, Kistarcsa 2143, Hungary B. Rojkovich Department of Rheumatology II, Polyclinic of the Hospital Brothers of St. John of God in Budapest, Frankel Leo´ u´t 54., Budapest 1023, Hungary J. van Exel W. B. F. Brouwer Institute of Health Policy and Management, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Rheumatologists’ estimates were similar, and they expected significant decrease of 2.3 on the DAS28. Actual scores after three months were obtained for 77 patients. The measured scores were significantly lower than expected scores for the HAQ-DI and EQ-5D. Rheumatologists’ expectations for the DAS28 score were not significantly different from measured scores. Patients’ average expectations regarding quality of life scores for ages 60, 70, 80 and 90 were 0.44, 0.24, 0.06 and -0.02, respectively. Our results suggest that both RA patients and rheumatologists expect quick and significant health improvements from biological drugs and tend to overestimate actual short term treatment effects. Nonetheless, RA patients expect a sharp deterioration of future health. Keywords Arthritis, rheumatoid Biological drugs Health expectations EQ-5D Hungary JEL Classification
I19
Introduction Rheumatoid arthritis (RA) is a chronic disease characterized by pain, stiffness, swelling, limited motion and function of many joints. RA is one of the most disabling types of arthritis and its burden goes far beyond the joints as it is associated with multiple comorbidities, psychosocial impairments and high direct and indirect costs both for patients and society [1, 2]. Treatment of RA has dramatically changed in the past decades [3]. After the expansion of treatment with conventional synthetic disease modifying antirheumatic drugs (csDMARD), in the late 1990s genetically engineered proteins have been shown to be effective in reducing symptoms and preventing structural
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damage in patients suffering from moderate to severe RA, who have not responded to csDMARDs. This new therapeutic group was labelled as biologic targeted therapies (also known as biologic response modifier drugs, biologicals or bDMARDs). Currently, nine bDMARDs are registered for the treatment of RA in Europe [4]. The availability of a wide spectrum of DMARDs that can slow down or even end disease progression, maintaining a good quality of life and work performance has become a real opportunity for RA patients. However, the new RA treatments are often very expensive, which necessitates clear decisions regarding how to optimally use these drugs [4, 5]. Besides more general guidance (through reimbursement decisions and medical guidelines), patients and physicians will play an important role in the actual treatment choices in RA. Such decisions will be influenced by the available scientific evidence and guidelines, but subjective expectations of patients and physicians about the effectiveness of such treatments may also have considerable influence on these decisions, including those regarding the start and continuation of treatment. To illustrate, high expectations of the effectiveness of new biologicals in patients and/or physicians may result in relatively quick uptake of such drugs. However, if these expectations are not met in reality, and, for instance, side effects of the drugs are more severe than expected, disappointment may result in decisions to discontinue treatment. Bendtsen et al. [6] already emphasised that patient preferences and expectations with regard to the outcome of pharmacological interventions are important parameters to assess in RA. Epstein [7] moreover pointed out that open trials of anti-CD4 monoclonal antibody in RA resulted in positive clinical benefits whilst the blinded, placebo controlled ones did not. One possible explanation for this difference in results might be the occurrence of expectation bias. Hence, Kvien and colleagues [8] argued that measuring expectations about future health and satisfaction with health may represent alternative approaches in the clinical assessment in RA. Obviously, not only the expectations of patients matter. As Simon [9] indicated, in parallel with the dramatical changes in the treatment possibilities for RA, expectations of patients as well as their clinicians changed. In turn, this may alter treatment choices. In that context, the suggestion of Alcorn et al. [10] to place more emphasis in treatment choices on how to best meet the treatment expectations of both clinicians and patients, is important. The subjective expectations of patients and physicians regarding the effectiveness of RA treatments, therefore, is an important issue, yet currently underexplored [11]. Moreover, according to our knowledge, it has never been studied how expected health changes match with actual therapeutic results of biological drugs. In addition, more
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general expectations regarding future health and longevity may influence treatment decisions. In general, little is known about such expectations [12–14] and methodological heterogeneity hampers comparability between studies. Among RA patients, Marshall et al. [15] performed a qualitative study in the early era of biologicals, and they found that RA patients expressed hope with the biological treatment, although not always high expectations. In a recent study, patients with biologicals had higher expectations for treatment compared to the csDMARDs group and after experiencing clinical remission, they increased their expectations and hoped to have their symptoms eradicated with current treatment [16]. On the other hand, a higher percentage of patients in the biological group showed disappointment with treatment as compared to the csDMARDs group although the reasons were different (primary or secondary failure vs. side effects). Bergsten et al. [17] explored healthcare providers’ experiences and highlighted that difficulties can arise in the interaction when patients’ expectations and preferences are not taken into account when giving medical advice. Buitinga et al. [18] performed a focus group study and asked RA patients about the expected future impact of RA and worst-case future scenarios. Besides reporting some important concerns (e.g., fear of becoming dependent, disappearance of expertise as a result of better career perspectives for physicians elsewhere) patients expressed hope and positive feelings toward continuous medication improvements. The authors proposed to develop interventions that teach patients to cope with their concerns and to put subjective beliefs into a realistic perspective. This study aims to contribute to the knowledge about the expectations of RA patients and their physicians regarding the effects of biological treatment and their future health. We performed an explorative study in which the subjective expectations of RA patients and their physicians were measured. Moreover, we compared the expected effects of biological treatment with actual effects after three months. Finally, we explored RA patients’ health expectations at older age.
Patients and methods Patients and study design A cross-sectional survey was performed in 12 hospital based rheumatology centres in Hungary in 2009. RA patients attending outpatient routine care to initiate their first biological therapy were invited to participate in this non-interventional study. A self-completed research questionnaire was designed for this study, consisting of two separate parts. The first part was designed for patients and
Subjective health expectations at biological therapy
the second for their treating rheumatologists. Both parts contained questions on the current health status of the patient and the expected changes for the future. Patients and rheumatologists were surveyed at baseline (Visit 1) and a follow-up was performed after three months (Visit 2). An informed consent form was signed. The research was carried out in compliance with the Helsinki Declaration. Authorization by the national ethical committee was obtained (ETT-TUKEB 8-66/2009-1018EKU). Assessment of current health status The patients’ questionnaire was handed to the participants by their rheumatologists. First, respondents were asked about demographics and to complete the HAQ-DI and the EQ-5D. The HAQ-DI consists of 20 questions in eight categories of functioning (dressing, rising, eating, walking, hygiene, reach, grip, and usual activities) and patients are asked to mark the level of difficulty they have in performing each particular task (without any difficulty, with some difficulty, with much difficulty, and unable to do). The highest component score determines the score of the category and the eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled) [19]. Current general health status was assessed by the validated Hungarian version of the EQ-5D questionnaire [20]. The EQ-5D involves a descriptive system (EQ-5D-3L) covering five health domains (mobility, self-care, daily activities, pain/discomfort, and anxiety/depression) with 3-level responses (no/mild/severe problems) and a standard vertical 20 cm visual analogue scale (EQ VAS) for recording the individual’s rating of his/her current health status. Each health state described by the descriptive system can be converted to a single health-related quality of life utility score (EQ5D score). Due to lack of national Hungarian tariffs, the UK utility scores were used in this study [21]. Higher EQ5D and EQ VAS scores correspond to a better health state. Both the EQ-5D and HAQ-DI have been validated for and widely used in RA [22]. Rheumatologists provided data on disease history, previous and current disease modifying antirheumatic drugs (DMARD) treatment. Disease activity was assessed by a composite score, the disease activity index (DAS28), which is calculated from the number of tender and swollen joints considering 28 specific joints, patients’ assessment of disease activity on a visual analogue scale (patient VAS), and the Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP). The DAS28 measures disease activity at a single point, and it can be used either as an absolute level, as a goal for the therapeutic intervention or as a tool to assess the improvement compared to baseline [4, 23, 24].
Assessment of subjective expectations of health at 3-months In the second section of the patients’ questionnaire, RA patients were asked to indicate the health status they expected to have after three months of initiation of biological treatment. The EQ-5D-3L descriptive system, EQ VAS, and HAQ-DI were used for this purpose, but the time-frame of these instruments was modified (e.g., EQ5D-3L: ‘…please indicate which statements will best describe your own health state in 3 months; HAQ-DI: Please place an ‘‘X’’ in the box which will best describe your abilities in 3 months’) and a short explanation was also provided. Similarly, rheumatologists were asked to estimate the patients’ health status on the EQ-5D-3L, EQ VAS and HAQ-DI in three months’ time, as well as their DAS28 score. Assessment of subjective expectations of health at older age The third section of the patients’ questionnaire contained questions on participant’s expectations regarding their health status at ages 60, 70, 80 and 90 years, using the descriptive system of the EQ-5D. Respondents were asked to indicate which level of impairment in the five domains they expect to have at these ages (see ‘‘Appendix’’). This method was previously successfully used in population surveys in the Netherlands and in Hungary [13, 14]. Patients were also asked about their life expectancy, as previously done [13, 14]. Responses were compared to age and gender matched statistical life expectancy in Hungary provided by the Hungarian Central Statistical Office. Assessments at follow-up According to the guidelines in Hungary, RA patients taking up biological therapy have to be monitored every three months. In the course of these routine visits, three months after take-up, we recorded patients’ main clinical data and measured their health status using the HAQ-DI and EQ-5D questionnaires. Statistical methods IBM SPSS, Release 20.0 (IBM, Armonk, NY, USA) was used for the analysis. Descriptive statistics were performed, actual and estimated scores were compared by paired sample t test. Explanatory factors associated with subjective health expectations were investigated by linear regression.
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M. Pe´ntek et al. Table 1 Baseline characteristics of RA patients initiating first biological therapy (at Visit 1)
Variables
Total patient sample at Visit 1; mean (SD)/number of patients (%)
Number of patients
92 (100 %)
Patient subsample at Visit 2; mean (SD)/ number of patients (%) 77 (100 %)
Patient characteristics Females
81 (88 %)
Age, years
51.1 (11.9)
66 (86 %) 51.4 (11.9)
Educational level Primary school
27 (29 %)
23(30 %)
Secondary school University (B.Sc. or M.Sc.)
46 (50 %) 19 (21 %)
38(49 %) 16 (21%)
Works full or part-time
26 (28 %)
22(29 %)
Disability pensioner
41 (45 %)
32(42 %)
Retired
16 (17 %)
14(18 %)
9 (10 %)
9 (11 %)
Occupational status
Other Disease characteristics Disease duration, years
8.5 (7.5)
9.0 (7.9)
Erythrocite sedimentation rate, mm/h
34.1 (21.3)
33.8 (21.7)
Number of tender joints of the 28 joint count
13.8 (6.1)
14.2 (6.2)
Number of swollen joints of the 28 joint count
9.2 (5.4)
9.4 (5.5)
Patient’s assessment on disease activity, VASa
70.4 (15.7)
70.9 (15.9)
Disease activity score, DAS28-Wea
6.1 (0.9)
6.1 (0.9)
Functional status, HAQ-DI (0–3)a
1.5 (0.7)
1.4 (0.7)
0.36 (0.36) 48.1 (21.8)
0.36 (0.35) 48.4 (21.2)
b
Health status, EQ-5D score (-0.59 to 1.00) Health status, EQ VAS (0–100)b Treatment characteristics
Number of previous conventional synthetic DMARDs 1
12 (13 %)
9 (12)
2
46 (50 %)
38 (49)
C3
34 (37 %)
30 (39)
Biological DMARD started at Visit 1 a
Higher score corresponds to worse status
b
Higher score corresponds to better status
Adalimumab
26 (28 %)
22 (29 %)
Etanercept
26 (28 %)
22 (29 %)
Infliximab
40 (44 %)
33 (43 %)
Results Patient sample One hundred and sixteen RA patients were invited to participate in the study. At baseline (Visit 1), 92 RA patients and their rheumatologist (participation rate 79 %) provided complete data on all relevant outcomes (baseline DAS28, HAQ-DI, EQ-5D, EQ VAS scores and expected health states after three months). At follow-up (Visit 2) complete data on DAS28, HAQ-DI, EQ-5D and EQ VAS were obtained from 77 patients (84 % of the 92 patients). Main characteristics at baseline and follow-up are presented in Table 1. Comparisons between baseline and follow-up data were performed using the subsample of 77 patients who
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completed the questionnaire at both Visit 1 and Visit 2. These patients were not (statistically significantly) different from the remaining 15 patients in terms of age, disease duration or DAS28, HAQ-DI and EQ-5D scores at baseline. Subjective expectations of health at 3 months Patients’ and rheumatologists’ baseline scores and subjective expectations at three months of treatment are presented in Table 2. Both patients and rheumatologists expected a significant (p \ 0.01) improvement of functional and health status as a result of initiating the first biological therapy. Differences between patients’ and rheumatologists’ estimated scores on EQ-5D, EQ VAS and HAQ-DI at three months were not significant (p = 0.723,
Subjective health expectations at biological therapy Table 2 Subjective expectations at the initiation of first biological therapy: comparison of baseline scores with subjective expectations at three months (N = 92)
Health measures
Baseline score (Visit 1), mean (SD)
Subjective expectations at 3 months, mean (SD)
Difference between baseline and expected scores
HAQ-DIa Patients
1.465 (0.667)
0.645 (0.590)
0.819 (0.605)*
Rheumatologists
NA
0.670 (0.500)
0.795 (0.690)*
Patients
0.358 (0.358)
0.749 (0.290)
-0.391 (0.362)*
Rheumatologists
NA
0.738 (0.247)
-0.380 (0.404)*
EQ-5D scoreb
EQ VASb Patients
NA not applicable * p \ 0.01 a
Higher score corresponds to worse status
Rheumatologists
66.010 (20.783)
-17.935 (24.433)*
63.950 (17.348)
-15.870 (26.692)*
Disease activity score (DAS28)a
b
Higher score corresponds to better status
Rheumatologists
6.104 (0.853)
100%
100%
90%
90%
80%
3.770 (0.882)
2.335 (1.126)*
80%
40% 30%
HAQ -DI dimensions Unable to do
With some difficulty
With much difficulty
Without any difficulty
Fig. 1 Estimated levels of difficulty in the HAQ-DI domains for three months ahead by RA patients (N = 92) and treating rheumatologists
0.749 and 0.337, respectively). Both expected an improvement in health status in size of, on average, a 0.8 decrease in HAQ-DI score. Patients expected a 0.4 increase in EQ-5D score. Rheumatologists also expected a 0.4 better score than patients’ self-reported EQ-5D score at Visit 1. The expected changes are not only statistically significant, but also clinically relevant since in RA the minimally important differences in HAQ-DI and EQ-5D scores are 0.22 and 0.05, respectively [25]. Rheumatologists expected a sharp decrease of disease activity: mean disease activity was high (DAS28 [ 5.1) at the initiation of biological therapy, and physicians expected patients to achieve an average score near to the commonly used cut-off for low disease activity (DAS28 \ 3.2) after three months.
Mobility
Self-care
Usual activities Pain / discomfort
Physician
Patient
Common daily activities
Patient
Grip
Physician
Physician
Patient
Patient
Reach
Physician
Walking Hygiene
Physician
Patient
Physician
Physician
Patient
Patient
Eating
0%
Patient
Dressing Arising and grooming
Physician
Patient
Physician
10%
Physician
20%
0%
Patient
10%
Patient
20%
Physician
30%
50%
Patient
40%
60%
Physician
50%
70%
Patient
60%
Physician
70%
Rate of responses, %
Rate of responses, %
48.080 (21.823) NA
Anxiety / depression
EQ -5D dimensions Severe problem
Mild problem
No problem
Fig. 2 Estimated levels of health problems in the EQ-5D-3L domains for three months ahead by RA patients (N = 92) and treating rheumatologists
It is notable how similar the expected average scores on the HAQ-DI and EQ-5D were between patients and rheumatologists (Table 2). However, closer inspection of the scoring patterns showed differences on the underlying dimensions in both instruments. Figure 1 shows that on most dimensions of the HAQ-DI patients more often selected the two extreme scoring categories (‘unable to do’ and ‘without any difficulty’; 47.6 vs. 39.1 %, p \ 0.05) and rheumatologists selected the two middle scoring categories (‘with much difficulty’ and ‘with some difficulty’; 44.4 vs. 52.8 %, p \ 0.05). These differences were most prominent for the ‘Eating’ and ‘Common daily activities’ dimensions. Figure 2 shows that patients and rheumatologists also scored differently on the EQ-5D,
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M. Pe´ntek et al. Table 3 Comparison of expected scores at biological therapy initiation and RA patients’ measured values after three months (subsample with complete data on all relevant measures, N = 77)
Health measures
Baseline score (Visit 1)
Subjective expectations at 3 months (Visit 1)
Actual score after 3 months (Visit 2)
Difference between expected and actual scores (Visit 1–2)
1.442 (0.666)
0.644 (0.561)
0.957 (0.584)
-0.313 (0.509)*
NA
0.640 (0.493)
NA
-0.318 (0.645)*
HAQ-DIa Patients Rheumatologists EQ-5D scoreb Patients
0.356 (0.352)
0.744 (0.284)
0.629 (0.235)
0.115 (0.248)*
Rheumatologists
NA
0.750 (0.197)
NA
0.121 (0.280)* 1.727 (18.501)
EQ VASb * p \ 0.01 a
Higher score corresponds to worse status
b
Higher score corresponds to better status
Patients
48.400 (21.165)
65.650 (19.650)
63.920 (16.443)
Rheumatologists
NA
63.050 (17.539)
NA
-0.870 (19.426)
4.082 (1.231)
-0.257 (1.415)
Disease activity score (DAS28)a Rheumatologists
6.131 (0.896)
with rheumatologists slightly more often selecting the middle category, but not significantly so (‘mild problems’; 33 vs. 38 %, p = 0.178). In other words, RA patients and rheumatologists expect a similar substantial improvement in patients’ health after tkhree months due to biological treatment, but the underlying patterns of expected improvements differ. Comparison of subjective expectations and actual health at three months At follow-up (Visit 2), 85 (92 %) patients of the initial sample (N = 92) continued using their initial biologic drug and dosage, three (3 %) patients had switched their initial biological drug to another due to an adverse event, one (1 %) had dosage increased due to inefficacy and three (3 %) patients had to stop biological treatment. Proportions of treatment continuations of the subsample of 77 patients completing both questionnaires (at Visit 1 and Visit 2) were similar to those in the total sample (no change: 69 (90 %); dosage increase due to inefficacy: two (3 %); switch due to adverse event: two (3 %); switch due to inefficacy: one (1 %); stop of biological treatment and: three (4 %) patients). Comparisons of initial expectations and actual health scores after three months are presented on Table 3. Also in this subsample (N = 77), both rheumatologists and patients expected significant improvement of health with biological therapy on all outcomes and, indeed, significant improvements were achieved. Comparison of baseline estimations and follow-up scores indicates that both rheumatologists and patients significantly overestimated the improvement of functional and general health status on the HAQ-DI and EQ-5D, but that their estimations on the EQ-VAS were fairly accurate (p = 0.416 and p = 0.695,
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3.825 (0.867)
0,9 0,8 0,7 0,6
EQ -5D score , mean
NA not applicable
0,5 0,4 0,3 0,2 0,1 0
-0,1
60
70
80
90
Age, years Subjective health expectations for specific ages: a web -based population survey (Péntek et al, 2012)
Subjective health expectations for specific ages: RA patients initiating first biological therapy
Actual health status of the general population* (Szende et al, 2003)
Fig. 3 RA patients’ subjective expectations on health status for specific ages (60, 70, 80 and 90) compared to results of a previous population survey in Hungary and the actual health status of the general population [14, 21]. Asterisks indicates mean EQ-5D scores of age groups 55–64, 65–74, 75–84 and C85 years are presented
respectively). Rheumatologists’ estimates on the DAS28 were also not statistically different from actual values (p = 0.115).
Subjective health expectations at biological therapy
Subjective expectations of health at older age
Discussion
RA patients’ (N = 92) subjective expectations regarding their health status in the further future are presented in Fig. 3. It is notable that RA patients expect a sharp decrease of their health with age, from a health-related quality of life score of 0.436 at age 60 to -0.019 at age 90, which is just below the value of the state ‘dead’. These figures are considerably lower than those previously observed among the general population in Hungary [21] or expected by members of the general public in Hungary [14].
This explorative study aimed to investigate subjective expectations of RA patients and their physicians regarding the three months effectiveness of treatment with biologicals as well as the subjective expectations of RA patients regarding their general future health and longevity. Since such expectations may influence treatment decisions, treatment evaluation and treatment persistence, exploring them is important. A unique feature of this study is that we were also able to compare expected gains with actual gains after three months. We assessed expected health gains and future health in a sample of Hungarian RA patients and their rheumatologists. Our results indicate that RA patients, who are typically in poor health when starting treatment with biologicals, have high expectations of treatment with biologicals. They expected significant improvements within three months. This was also observed for their physicians. Expecting an improvement is not unrealistic, since HAQDI decreases due to treatment with biologicals have indeed been observed in clinical trials (albeit often measured after six months or one year) [26]. The degree of expected health gain was relatively high, however, both for patients and physicians. Our follow-up data indicated that the expected (sizeable) improvements in HAQ-DI and EQ-5D scores were not observed after three months. Expectations regarding EQ VAS scores and DAS28 (for physicians) proved to be more accurate. Educational level and age appeared to be associated with these expectations. RA patients moreover expected relatively poor health states at older ages as well as relatively short life duration. These findings are important, since overoptimistic expectations as observed here may cause patients and their physicians to be disappointed with the actual improvements in health. Similarly, slower improvement than anticipated or more initial side-effects may cause patients (and physicians) to undervalue the achieved improvements and to discontinue treatment. Before discussing some findings and implications in more detail, some limitations of our study need noting. First, our sample stemmed from a single country and was relatively small. Therefore, our results are not necessarily representative for Hungarian RA patients starting treatment with biologicals, nor for their rheumatologists, and the results cannot be generalised to other countries. Moreover, we only had a small subsample of male RA patients, which emphasises the need for caution in interpreting results and generalising results. Although we feel that the current sample was appropriate for our explorative purposes, we encourage new studies in other (and larger) samples, also in other countries. Second, a unique feature of our study was its longitudinal design which allowed comparing
Subjective expectations of length of life Altogether 86 patients (females: 76, males 10; response rate 93 %) completed the question regarding expected longevity. RA patients on average expected to live to the age of 78.1 (SD 11.2) years (females 78.7, SD 10.7 vs. males 73.7, SD 14.3; p = 0.187). This is a bit lower than the expectation observed in the Hungarian general public (total sample: 79.6, SD 10.8; females 80.3, SD 10.1; males 79.3, SD 11.2, see Pe´ntek et al., In press) [14]. The gender-matched and age-matched statistical life expectancy of the general population in Hungary is slightly higher than this expectation (mean 79.2, SD 2.9; females 79.9, SD 2.0; males 73.6, SD 2.7), but not significantly so. Determinants of RA patients’ subjective expectations Stepwise linear regression analysis showed that patients’ expectations about the effect of the treatment were associated with a limited number of characteristics. Expected HAQ-DI scores after three months were positively associated with age (p \ 0.05) and negatively with educational level (p \ 0.00). Expected EQ-5D scores after three months were negatively associated with age (p \ 0.05) and positively with educational level (p \ 0.01). In other words, older and lower educated RA patients expected to have a worse functional and health status three months after biological therapy initiation than their younger and higher educated counterparts. In addition, female patients expected higher EQ-5D scores after three months than male patients (p \ .01). The results for the accuracy of those expectations after three months, gave ambiguous results. Linear regression of the difference between expected scores at Visit 1 and actual scores at Visit 2 were positively associated with education level for HAQ (p \ 0.05), while these were negatively associated with educational level (p \ 0.01) and positively with employment status (p \ 0.05) for EQ-5D.
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expectations with actual health gains due to treatment. We used one follow-up after three months. Obviously, using a longer follow-up period or more follow-up moments might have yielded other results. We encourage new studies to investigate this further. Third, the similarities between physicians’ and patients’ expectations were, when considering average scores, striking. One might expect patients’ expectations to have been influenced by the information provided by their rheumatologists, which in turn may have been coloured by their expectations. The similarities between the average expectations for EQ-5D and HAQ-DI scores seem to support this hypothesis. However, patients’ and rheumatologists’ expectations were different at the level of the health domains, i.e., the type of activities and health dimensions they expected to improve with the therapy. Hence, the exact source of expectation formation remains unclear and seems a fruitful area for future research. Moreover, the sometimes subtle differences in expectations between patients and physicians deserve attention and highlight the importance of involving expectations in discussions between patients and physicians. Fourth, the instruments and methods for measuring expectations are not yet well developed. Here, we drew as much as possible on previously used methods [13, 14]. We have no indication that patients or rheumatologists considered the questionnaire to be difficult to comprehend or complete. Still, it cannot be ruled out that other ways of investigating expectations or the use of other instruments, would have resulted in different results. Notwithstanding these limitations, we feel that the findings of this study convey some important messages. Our results indicate that RA patients and their physicians appear to have (in some ways unrealistically) high expectations of treatment with biological treatments. The subjective expectations of patients may serve as an important reference point influencing patients’ disease and treatment assessment and compliance. Hence, the fact that patients and physicians are, in general, overly optimistic in their expectations regarding the treatment effects of biologicals (measured with EQ-5D and HAQ-DI scores) could imply that the actual improvements could be judged less favourable than had been the case if patients (and physicians) had lower expectations. It would be interesting to assess in future research how patients and physicians evaluate the gap between expectations and realisations. It was interesting to observe that the EQ VAS (patients) and DAS28 (rheumatologists) scores were more accurate when compared to actual treatment effects after three months than the EQ-5D and HAQ-DI scores. One potential cause of the more accurate estimation with these former tools might be that patients might be more familiar with VAS scores (since self-assessment on a VAS is part of regular RA care) and rheumatologists are more
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experienced with the DAS28 than with the other two quality of life questionnaires. Furthermore, estimating a single score might result in more accurate estimations than assessing expected improvement on a disaggregate descriptive questionnaire. The lack of validated questionnaires to assess expectations indicates an important area for future research. It does seem that this field is developing, underlining its importance. Ferrari and colleagues [27] for instance used the HAQ-DI in an imaginary scenario to assess university students’ expectations of disability if they had RA. Hofman et al. [28] have recently presented two initial phases of the development of a patient-generated treatment expectancy measure. Some items of this questionnaire assess health domains similar to those measured in the EQ-5D, HAQ-DI and DAS28 (e.g., mobility, pain, everyday activities, swelling of the joints). However, it includes additional aspects that RA patients considered relevant (e.g., visible signs of RA, joint damage, fatigue or reduce the likelihood of surgery). While such exploration of patients’ expectations undoubtedly yields richer insights, our approach was chosen in order to be able to compare expected and actual outcomes. Hence, we stayed close to well accepted measurement methods in the field of RA and our results show that this approach is feasible. The validity of our approach can be studied further in future studies. An interesting aspect of our study was the additional focus on long term health expectations among RA patients. In contrast to the (overly) optimistic expectations regarding the effectiveness of the treatment with biologicals, RA patients do expect a fairly sharp decline in health over time. Current health and functioning (EQ-5D and HAQ-DI) were found to be clearly related to long term health expectations (for ages 60, 70, 80 and 90). An EQ-5D score of 0.436 was expected for the age of 60 and further decline was expected for older ages. These figures were compared to those obtained in a sample of the Hungarian general public, using the same methodology [14] (see Fig. 3). While the declining trend in future quality of life and low scores for old ages was also observed there, but primarily for the ages 80 and 90, the expectations of RA patients were clearly lower than observed quality of life in Hungary for all older age groups. RA patients’ expectations were lower than those of the general public for all observed future ages. This difference was also observed when only considering the subsample of 45–54 years old from the general public sample, which better resemble the average age of the RA patients (N = 1,200; expected mean scores for ages 60, 70, 80 and 90: 0.76, 0.59, 0.32 and 0.04). Future research could focus on the quality of life expectations of RA patients for the years before the age of 60, also in relation to the expected treatment effects of biologicals. In depth (qualitative) analysis of the apparent discrepancy between expectations regarding future quality and length of life and
Subjective health expectations at biological therapy
treatment effects is encouraged as well. One potential explanation for the current findings is that RA patients might worry about or even fear the idea of growing old with RA and may expect the biologicals to only (effectively) postpone the ‘inevitable’ decline in quality of life. Given that real life data regarding the long term effects of biological treatments on quality of life are becoming available from various registries [29], the accuracy of expectations of RA patients can be further evaluated. Longer term health expectations could be explicitly discussed between patients and rheumatologists at initiation of and during treatment with biologicals. Deriving subjective life expectancy of RA patients also yielded some interesting results. RA patients with persistent high disease activity have an increased risk of mortality. Hence, a relatively low subjective life expectancy could be expected. However, it must be noted that observational studies confirmed that biological drugs may reduce premature mortality in RA patients when compared to other treatment regimens [30]. In this study, RA patients’ expectations regarding length of life were just below the gender and age-matched statistical life-expectancy of the Hungarian population (mean -1.1 years), but this difference was not statistically significant. While this indicates that RA patients may not have adjusted their life expectancy, this may not be fully accurate, since on average, people from the Hungarian general public appear to (considerably) overestimate their life expectancy, i.e., women 1.6 years and men 8.2 years [14], which was similar to the pattern found in The Netherlands [13]. Only considering the subsample of 45–54 years old in the Hungarian general public sample indicated an overestimation of 0.3 years for women and 7.7 years for men [14]. In the current study, such a pronounced gender difference was not observed, but our sample of men was too small to draw any firm conclusions on this matter. In general, it seems that RA patients have somewhat lower longevity expectations than their counterparts in the general public and their statistical life-expectancy. Future research could investigate these expectations further, including the question whether RA patients are aware of their increased mortality risk and how they expect biologicals to affect this. Regression analysis demonstrated that older and lower educated patients expected a worse health status after three months after initiation of biological treatment. However, for more insightful analysis of the determinants of expectations and their accuracy a larger sample is necessary in future studies. Further potential explanatory factors of subjective expectations, such as satisfaction with life in general and the health care system in particular, riskseeking or risk-averse health behaviour and access to health care are worth studying in the future.
In conclusion, we feel that this explorative study has emphasised the importance and feasibility of investigating subjective expectations regarding treatment effects and future length and quality of life in patients suffering from diseases such as RA. More research in this area is encouraged, because these expectations may influence treatment compliance, persistence and evaluation, as well as more general life-style choices, health spending and discounting. Better understanding of expectations of patients and physicians, in general regarding future health, and in particular regarding treatment effectiveness, remains an important objective. This paper hopes to have contributed to that goal. Acknowledgments Authors are grateful to the patients who participated in the survey and the following colleagues for assisting with the local data collection: Ange´la Fu¨lo¨p, Pa´l Ge´her, Ilona Ujfalussy and Magdolna Tandari (Budapest); Zolta´n Szekanecz, No´ra Bodna´r, Gabriella Sz} ucs, Szilvia Szamosi and Andrea Va´ncsa (Debrecen); Pe´ter Keszthelyi, Hajnalka Kova´cs, Kla´ra Abruda´n and Zsuzsa ´ gnes Edit To´th, Gyo¨ngyi Za´vada (Gyula); Ferenc Szanyo´ (Gy} or); A Bo¨jte, Annama´ria Eiben and Gre´ta Sterba (Kistarcsa); La´szlo´ Tama´si, ´ gnes Flo´ria´n and Katalin Luka´cs (Miskolc); Tibor Katalin Fazekas, A Varju´, Zita Szabo´, Erzse´bet Encs and Andrea Tisza (Nyı´regyha´za); La´szlo´ Kova´cs, Attila Balogh and Daniella Hullo´ (Szeged); Attila Kova´cs, Bea´ta Baksay, Judit Bı´ro´ and Katalin Ga´csi (Szolnok); Lilla Na´fra´di (Szombathely); La´szlo´ Czirja´k, Do´ra Niedermayer and Cecı´lia Varju´ (Pe´cs). The survey was supported by an independent grant from the Centre for Public Affairs Studies Foundation and HTA Co.
Appendix Questionnaire used in the survey: expected health problems at ages 60, 70, 80 and 90 were asked applying the statements of the EQ-5D.
I think at age 60 I will have… (Please mark your response) a.
No
Some
Major
Problems with walking about
b.
No
Some
Major
Problems with washing or dressing
c.
No
Some
Major
Problems with performing usual activities
d.
No
Some
Severe
Pain or discomfort
e.
No
Some
Severe
Anxiety or depression
Ages 70, 80 and 90 were asked in a same construct
References 1. Boonen, A., Severens, J.L.: The burden of illness of rheumatoid arthritis. Clin. Rheumatol. 30(Suppl 1), S3–S8 (2011) 2. Furneri, G., Mantovani, L.G., Belisari, A., Mosca, M., Cristiani, M., Bellelli, S., Cortesi, P.A., Turchetti, G.: Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. Clin. Exp. Rheumatol. 30(4 Suppl 73), S72–S84 (2012)
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M. Pe´ntek et al. 3. Upchurch, K.S., Kay, J.: Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford) 51(Suppl 6), vi28–vi36 (2012) 4. Smolen, J.S., Landewe, R., Breedveld, F.C., Buch, M., Burmester, G., Dougados, M., Emery, P., Gaujoux-Viala, C., Gossec, L., Nam, J., Ramiro, S., Winthrop, K., de Wit, M., Aletaha, D., Betteridge, N., Bijlsma, J.W., Boers, M., Buttgereit, F., Combe, B., Cutolo, M., Damjanov, N., Hazes, J.M., Kouloumas, M., Kvien, T.K., Mariette, X., Pavelka, K., van Riel, P.L., RubbertRoth, A., Scholte-Voshaar, M., Scott, D.L., Sokka-Isler, T., Wong, J.B., van der Heijde, D.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann. Rheum. Dis. 73(3), 492–509 (2014) 5. Kobelt, G., Jonsson, B.: The burden of rheumatoid arthritis and access to treatment: outcome and cost-utility of treatments. Eur J Health Econ 8(Suppl 2), 95–106 (2008) 6. Bendtsen, P., Akerlind, I., Hornquist, J.O.: Pharmacological intervention in older patients with rheumatoid arthritis. Quality of life aspects. Drugs Aging 7(5), 338–346 (1995) 7. Epstein, W.V.: Expectation bias in rheumatoid arthritis clinical trials. The anti-CD4 monoclonal antibody experience. Arthritis Rheum. 39(11), 1773–1780 (1996) 8. Kvien, T.K., Heiberg, T.: Patient perspective in outcome assessments–perceptions or something more? J. Rheumatol. 30(4), 873–876 (2003) 9. Simon, L.S.: The treatment of rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 18(4), 507–538 (2004) 10. Alcorn, N., Waite, L., Madhok, R.: Transforming the expectations of patients with rheumatoid arthritis? Rheumatology (Oxford) 49(7), 1211–1212 (2010) 11. van Vollenhoven, R.F.: Unresolved issues in biologic therapy for rheumatoid arthritis. Nat. Rev. Rheumatol. 7(4), 205–215 (2011) 12. Mirowsky, J.: Subjective life expectancy in the US: correspondence to actuarial estimates by age, sex and race. Soc. Sci. Med. 49(7), 967–979 (1999) 13. Brouwer, W.B., van Exel, N.J.: Expectations regarding length and health related quality of life: some empirical findings. Soc. Sci. Med. 61(5), 1083–1094 (2005) 14. Pentek, M., Brodszky, V., Gulacsi, A.L., Hajdu, O., van Exel, J., Brouwer, W., Gulacsi, L.: Subjective expectations regarding length and health-related quality of life in Hungary: results from an empirical investigation. Health Expect. (2012). doi:10.1111/j. 1369-7625.2012.00797.x 15. Marshall, N.J., Wilson, G., Lapworth, K., Kay, L.J.: Patients’ perceptions of treatment with anti-TNF therapy for rheumatoid arthritis: a qualitative study. Rheumatology (Oxford) 43(8), 1034–1038 (2004) 16. Funahashi, K., Matsubara, T.: What RA patients expect of their treatment–discussion over the result of our survey. Clin. Rheumatol. 31(11), 1559–1566 (2012) 17. Bergsten, U., Bergman, S., Fridlund, B., Arvidsson, B.: Delivering knowledge and advice: healthcare providers’ experiences of
123
18.
19.
20.
21. 22.
23.
24.
25.
26.
27.
28.
29.
30.
their interaction with patients’ management of rheumatoid arthritis. Int. J. Qual. Stud. Health Well-being 6(4) (2011) Buitinga, L., Braakman-Jansen, L.M., Taal, E., van de Laar, M.A.: Future expectations and worst-case future scenarios of patients with rheumatoid arthritis: a focus group study. Musculoskelet. Care 10(4), 240–247 (2012) Bruce, B., Fries, J.F.: The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual. Life Outcomes 1, 20 (2003) EuroQoL-Group: EuroQol: a new facility for the measurement of health-related quality of life. Health Policy 16(3), 199–208 (1990) Szende, A., Nemeth, R.: Health-related quality of life of the Hungarian population. Orv. Hetil. 144(34), 1667–1674 (2003) Lillegraven, S., Kvien, T.K.: Measuring disability and quality of life in established rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 21(5), 827–840 (2007) Anderson, J., Caplan, L., Yazdany, J., Robbins, M.L., Neogi, T., Michaud, K., Saag, K.G., O’Dell, J.R., Kazi, S.: Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis. Care Res. (Hoboken) 64(5), 640–647 (2012) Hobbs, K.F., Cohen, M.D.: Rheumatoid arthritis disease measurement: a new old idea. Rheumatology (Oxford) 51(Suppl 6), vi21–vi27 (2012) Marra, C.A., Woolcott, J.C., Kopec, J.A., Shojania, K., Offer, R., Brazier, J.E., Esdaile, J.M., Anis, A.H.: A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis. Soc. Sci. Med. 60(7), 1571–1582 (2005) Schmitz, S., Adams, R., Walsh, C.D., Barry, M., FitzGerald, O.: A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach. Ann. Rheum. Dis. 71(2), 225–230 (2012) Ferrari, R., Russell, A.S.: Correlations between coping styles and symptom expectation for rheumatoid arthritis. Clin. Rheumatol. 29(12), 1445–1448 (2010) Hofmann, D., Ibrahim, F., Rose, D., Scott, D.L., Cope, A., Wykes, T., Lempp, H.: Expectations of new treatment in rheumatoid arthritis: developing a patient-generated questionnaire. Health Expect. (2013). doi:10.1111/hex.12073 Yoshida, K., Radner, H., Kavanaugh, A., Sung, Y.K., Bae, S.C., Kishimoto, M., Matsui, K., Okada, M., Tohma, S., Weinblatt, M.E., Solomon, D.H.: Use of data from multiple registries in studying biologic discontinuation: challenges and opportunities. Clin. Exp. Rheumatol. 31(4 Suppl 78), S28–S32 (2013) Listing, J., Kekow, J., Manger, B., Burmester, G.R., Pattloch, D., Zink, A., Strangfeld, A.: Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann. Rheum. Dis. (2013). doi:10. 1136/annrheumdis-2013-204021
ORIGINAL PAPER
Subjective health expectations at biological therapy initiation: a survey of rheumatoid arthritis patients and rheumatologists Ma´rta Pe´ntek • La´szlo´ Gula´csi • Bernadette Rojkovich • Valentin Brodszky • Job van Exel • Werner B. F. Brouwer
Received: 7 February 2014 / Accepted: 31 March 2014 Springer-Verlag Berlin Heidelberg 2014
Abstract Subjective health expectations of patients with rheumatoid arthritis (RA) and rheumatologists remain understudied. We measured subjective expectations regarding treatment effects of biologicals as well as future length and quality of life. Moreover, we compared expectations regarding treatment effects to actual treatment effects. We recruited a sample of Hungarian RA patients initiating treatment with biologicals. Expectations regarding treatment effects and future health were obtained through a written questionnaire from patients and physicians, including functional impairment (HAQ-DI), health status (EQ-5D) and disease activity (DAS28). After three months, actual treatment effects were obtained. Ninety-two RA patients (females N = 81, 88 %) with mean age of 51 (SD 12) and disease duration of 9 (SD 8) years with high average disease activity (DAS28: 6.1) were included. Patients expected significant and large health improvement within three months with mean changes on the HAQ-DI of -0.8 and on the EQ-5D of ?0.4. M. Pe´ntek (&) L. Gula´csi V. Brodszky Department of Health Economics, Corvinus University of Budapest, F}ova´m te´r 8, Budapest 1093, Hungary e-mail: [email protected] M. Pe´ntek Department of Rheumatology, Flo´r Ferenc County Hospital, Semmelweis te´r 1, Kistarcsa 2143, Hungary B. Rojkovich Department of Rheumatology II, Polyclinic of the Hospital Brothers of St. John of God in Budapest, Frankel Leo´ u´t 54., Budapest 1023, Hungary J. van Exel W. B. F. Brouwer Institute of Health Policy and Management, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Rheumatologists’ estimates were similar, and they expected significant decrease of 2.3 on the DAS28. Actual scores after three months were obtained for 77 patients. The measured scores were significantly lower than expected scores for the HAQ-DI and EQ-5D. Rheumatologists’ expectations for the DAS28 score were not significantly different from measured scores. Patients’ average expectations regarding quality of life scores for ages 60, 70, 80 and 90 were 0.44, 0.24, 0.06 and -0.02, respectively. Our results suggest that both RA patients and rheumatologists expect quick and significant health improvements from biological drugs and tend to overestimate actual short term treatment effects. Nonetheless, RA patients expect a sharp deterioration of future health. Keywords Arthritis, rheumatoid Biological drugs Health expectations EQ-5D Hungary JEL Classification
I19
Introduction Rheumatoid arthritis (RA) is a chronic disease characterized by pain, stiffness, swelling, limited motion and function of many joints. RA is one of the most disabling types of arthritis and its burden goes far beyond the joints as it is associated with multiple comorbidities, psychosocial impairments and high direct and indirect costs both for patients and society [1, 2]. Treatment of RA has dramatically changed in the past decades [3]. After the expansion of treatment with conventional synthetic disease modifying antirheumatic drugs (csDMARD), in the late 1990s genetically engineered proteins have been shown to be effective in reducing symptoms and preventing structural
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M. Pe´ntek et al.
damage in patients suffering from moderate to severe RA, who have not responded to csDMARDs. This new therapeutic group was labelled as biologic targeted therapies (also known as biologic response modifier drugs, biologicals or bDMARDs). Currently, nine bDMARDs are registered for the treatment of RA in Europe [4]. The availability of a wide spectrum of DMARDs that can slow down or even end disease progression, maintaining a good quality of life and work performance has become a real opportunity for RA patients. However, the new RA treatments are often very expensive, which necessitates clear decisions regarding how to optimally use these drugs [4, 5]. Besides more general guidance (through reimbursement decisions and medical guidelines), patients and physicians will play an important role in the actual treatment choices in RA. Such decisions will be influenced by the available scientific evidence and guidelines, but subjective expectations of patients and physicians about the effectiveness of such treatments may also have considerable influence on these decisions, including those regarding the start and continuation of treatment. To illustrate, high expectations of the effectiveness of new biologicals in patients and/or physicians may result in relatively quick uptake of such drugs. However, if these expectations are not met in reality, and, for instance, side effects of the drugs are more severe than expected, disappointment may result in decisions to discontinue treatment. Bendtsen et al. [6] already emphasised that patient preferences and expectations with regard to the outcome of pharmacological interventions are important parameters to assess in RA. Epstein [7] moreover pointed out that open trials of anti-CD4 monoclonal antibody in RA resulted in positive clinical benefits whilst the blinded, placebo controlled ones did not. One possible explanation for this difference in results might be the occurrence of expectation bias. Hence, Kvien and colleagues [8] argued that measuring expectations about future health and satisfaction with health may represent alternative approaches in the clinical assessment in RA. Obviously, not only the expectations of patients matter. As Simon [9] indicated, in parallel with the dramatical changes in the treatment possibilities for RA, expectations of patients as well as their clinicians changed. In turn, this may alter treatment choices. In that context, the suggestion of Alcorn et al. [10] to place more emphasis in treatment choices on how to best meet the treatment expectations of both clinicians and patients, is important. The subjective expectations of patients and physicians regarding the effectiveness of RA treatments, therefore, is an important issue, yet currently underexplored [11]. Moreover, according to our knowledge, it has never been studied how expected health changes match with actual therapeutic results of biological drugs. In addition, more
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general expectations regarding future health and longevity may influence treatment decisions. In general, little is known about such expectations [12–14] and methodological heterogeneity hampers comparability between studies. Among RA patients, Marshall et al. [15] performed a qualitative study in the early era of biologicals, and they found that RA patients expressed hope with the biological treatment, although not always high expectations. In a recent study, patients with biologicals had higher expectations for treatment compared to the csDMARDs group and after experiencing clinical remission, they increased their expectations and hoped to have their symptoms eradicated with current treatment [16]. On the other hand, a higher percentage of patients in the biological group showed disappointment with treatment as compared to the csDMARDs group although the reasons were different (primary or secondary failure vs. side effects). Bergsten et al. [17] explored healthcare providers’ experiences and highlighted that difficulties can arise in the interaction when patients’ expectations and preferences are not taken into account when giving medical advice. Buitinga et al. [18] performed a focus group study and asked RA patients about the expected future impact of RA and worst-case future scenarios. Besides reporting some important concerns (e.g., fear of becoming dependent, disappearance of expertise as a result of better career perspectives for physicians elsewhere) patients expressed hope and positive feelings toward continuous medication improvements. The authors proposed to develop interventions that teach patients to cope with their concerns and to put subjective beliefs into a realistic perspective. This study aims to contribute to the knowledge about the expectations of RA patients and their physicians regarding the effects of biological treatment and their future health. We performed an explorative study in which the subjective expectations of RA patients and their physicians were measured. Moreover, we compared the expected effects of biological treatment with actual effects after three months. Finally, we explored RA patients’ health expectations at older age.
Patients and methods Patients and study design A cross-sectional survey was performed in 12 hospital based rheumatology centres in Hungary in 2009. RA patients attending outpatient routine care to initiate their first biological therapy were invited to participate in this non-interventional study. A self-completed research questionnaire was designed for this study, consisting of two separate parts. The first part was designed for patients and
Subjective health expectations at biological therapy
the second for their treating rheumatologists. Both parts contained questions on the current health status of the patient and the expected changes for the future. Patients and rheumatologists were surveyed at baseline (Visit 1) and a follow-up was performed after three months (Visit 2). An informed consent form was signed. The research was carried out in compliance with the Helsinki Declaration. Authorization by the national ethical committee was obtained (ETT-TUKEB 8-66/2009-1018EKU). Assessment of current health status The patients’ questionnaire was handed to the participants by their rheumatologists. First, respondents were asked about demographics and to complete the HAQ-DI and the EQ-5D. The HAQ-DI consists of 20 questions in eight categories of functioning (dressing, rising, eating, walking, hygiene, reach, grip, and usual activities) and patients are asked to mark the level of difficulty they have in performing each particular task (without any difficulty, with some difficulty, with much difficulty, and unable to do). The highest component score determines the score of the category and the eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled) [19]. Current general health status was assessed by the validated Hungarian version of the EQ-5D questionnaire [20]. The EQ-5D involves a descriptive system (EQ-5D-3L) covering five health domains (mobility, self-care, daily activities, pain/discomfort, and anxiety/depression) with 3-level responses (no/mild/severe problems) and a standard vertical 20 cm visual analogue scale (EQ VAS) for recording the individual’s rating of his/her current health status. Each health state described by the descriptive system can be converted to a single health-related quality of life utility score (EQ5D score). Due to lack of national Hungarian tariffs, the UK utility scores were used in this study [21]. Higher EQ5D and EQ VAS scores correspond to a better health state. Both the EQ-5D and HAQ-DI have been validated for and widely used in RA [22]. Rheumatologists provided data on disease history, previous and current disease modifying antirheumatic drugs (DMARD) treatment. Disease activity was assessed by a composite score, the disease activity index (DAS28), which is calculated from the number of tender and swollen joints considering 28 specific joints, patients’ assessment of disease activity on a visual analogue scale (patient VAS), and the Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP). The DAS28 measures disease activity at a single point, and it can be used either as an absolute level, as a goal for the therapeutic intervention or as a tool to assess the improvement compared to baseline [4, 23, 24].
Assessment of subjective expectations of health at 3-months In the second section of the patients’ questionnaire, RA patients were asked to indicate the health status they expected to have after three months of initiation of biological treatment. The EQ-5D-3L descriptive system, EQ VAS, and HAQ-DI were used for this purpose, but the time-frame of these instruments was modified (e.g., EQ5D-3L: ‘…please indicate which statements will best describe your own health state in 3 months; HAQ-DI: Please place an ‘‘X’’ in the box which will best describe your abilities in 3 months’) and a short explanation was also provided. Similarly, rheumatologists were asked to estimate the patients’ health status on the EQ-5D-3L, EQ VAS and HAQ-DI in three months’ time, as well as their DAS28 score. Assessment of subjective expectations of health at older age The third section of the patients’ questionnaire contained questions on participant’s expectations regarding their health status at ages 60, 70, 80 and 90 years, using the descriptive system of the EQ-5D. Respondents were asked to indicate which level of impairment in the five domains they expect to have at these ages (see ‘‘Appendix’’). This method was previously successfully used in population surveys in the Netherlands and in Hungary [13, 14]. Patients were also asked about their life expectancy, as previously done [13, 14]. Responses were compared to age and gender matched statistical life expectancy in Hungary provided by the Hungarian Central Statistical Office. Assessments at follow-up According to the guidelines in Hungary, RA patients taking up biological therapy have to be monitored every three months. In the course of these routine visits, three months after take-up, we recorded patients’ main clinical data and measured their health status using the HAQ-DI and EQ-5D questionnaires. Statistical methods IBM SPSS, Release 20.0 (IBM, Armonk, NY, USA) was used for the analysis. Descriptive statistics were performed, actual and estimated scores were compared by paired sample t test. Explanatory factors associated with subjective health expectations were investigated by linear regression.
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M. Pe´ntek et al. Table 1 Baseline characteristics of RA patients initiating first biological therapy (at Visit 1)
Variables
Total patient sample at Visit 1; mean (SD)/number of patients (%)
Number of patients
92 (100 %)
Patient subsample at Visit 2; mean (SD)/ number of patients (%) 77 (100 %)
Patient characteristics Females
81 (88 %)
Age, years
51.1 (11.9)
66 (86 %) 51.4 (11.9)
Educational level Primary school
27 (29 %)
23(30 %)
Secondary school University (B.Sc. or M.Sc.)
46 (50 %) 19 (21 %)
38(49 %) 16 (21%)
Works full or part-time
26 (28 %)
22(29 %)
Disability pensioner
41 (45 %)
32(42 %)
Retired
16 (17 %)
14(18 %)
9 (10 %)
9 (11 %)
Occupational status
Other Disease characteristics Disease duration, years
8.5 (7.5)
9.0 (7.9)
Erythrocite sedimentation rate, mm/h
34.1 (21.3)
33.8 (21.7)
Number of tender joints of the 28 joint count
13.8 (6.1)
14.2 (6.2)
Number of swollen joints of the 28 joint count
9.2 (5.4)
9.4 (5.5)
Patient’s assessment on disease activity, VASa
70.4 (15.7)
70.9 (15.9)
Disease activity score, DAS28-Wea
6.1 (0.9)
6.1 (0.9)
Functional status, HAQ-DI (0–3)a
1.5 (0.7)
1.4 (0.7)
0.36 (0.36) 48.1 (21.8)
0.36 (0.35) 48.4 (21.2)
b
Health status, EQ-5D score (-0.59 to 1.00) Health status, EQ VAS (0–100)b Treatment characteristics
Number of previous conventional synthetic DMARDs 1
12 (13 %)
9 (12)
2
46 (50 %)
38 (49)
C3
34 (37 %)
30 (39)
Biological DMARD started at Visit 1 a
Higher score corresponds to worse status
b
Higher score corresponds to better status
Adalimumab
26 (28 %)
22 (29 %)
Etanercept
26 (28 %)
22 (29 %)
Infliximab
40 (44 %)
33 (43 %)
Results Patient sample One hundred and sixteen RA patients were invited to participate in the study. At baseline (Visit 1), 92 RA patients and their rheumatologist (participation rate 79 %) provided complete data on all relevant outcomes (baseline DAS28, HAQ-DI, EQ-5D, EQ VAS scores and expected health states after three months). At follow-up (Visit 2) complete data on DAS28, HAQ-DI, EQ-5D and EQ VAS were obtained from 77 patients (84 % of the 92 patients). Main characteristics at baseline and follow-up are presented in Table 1. Comparisons between baseline and follow-up data were performed using the subsample of 77 patients who
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completed the questionnaire at both Visit 1 and Visit 2. These patients were not (statistically significantly) different from the remaining 15 patients in terms of age, disease duration or DAS28, HAQ-DI and EQ-5D scores at baseline. Subjective expectations of health at 3 months Patients’ and rheumatologists’ baseline scores and subjective expectations at three months of treatment are presented in Table 2. Both patients and rheumatologists expected a significant (p \ 0.01) improvement of functional and health status as a result of initiating the first biological therapy. Differences between patients’ and rheumatologists’ estimated scores on EQ-5D, EQ VAS and HAQ-DI at three months were not significant (p = 0.723,
Subjective health expectations at biological therapy Table 2 Subjective expectations at the initiation of first biological therapy: comparison of baseline scores with subjective expectations at three months (N = 92)
Health measures
Baseline score (Visit 1), mean (SD)
Subjective expectations at 3 months, mean (SD)
Difference between baseline and expected scores
HAQ-DIa Patients
1.465 (0.667)
0.645 (0.590)
0.819 (0.605)*
Rheumatologists
NA
0.670 (0.500)
0.795 (0.690)*
Patients
0.358 (0.358)
0.749 (0.290)
-0.391 (0.362)*
Rheumatologists
NA
0.738 (0.247)
-0.380 (0.404)*
EQ-5D scoreb
EQ VASb Patients
NA not applicable * p \ 0.01 a
Higher score corresponds to worse status
Rheumatologists
66.010 (20.783)
-17.935 (24.433)*
63.950 (17.348)
-15.870 (26.692)*
Disease activity score (DAS28)a
b
Higher score corresponds to better status
Rheumatologists
6.104 (0.853)
100%
100%
90%
90%
80%
3.770 (0.882)
2.335 (1.126)*
80%
40% 30%
HAQ -DI dimensions Unable to do
With some difficulty
With much difficulty
Without any difficulty
Fig. 1 Estimated levels of difficulty in the HAQ-DI domains for three months ahead by RA patients (N = 92) and treating rheumatologists
0.749 and 0.337, respectively). Both expected an improvement in health status in size of, on average, a 0.8 decrease in HAQ-DI score. Patients expected a 0.4 increase in EQ-5D score. Rheumatologists also expected a 0.4 better score than patients’ self-reported EQ-5D score at Visit 1. The expected changes are not only statistically significant, but also clinically relevant since in RA the minimally important differences in HAQ-DI and EQ-5D scores are 0.22 and 0.05, respectively [25]. Rheumatologists expected a sharp decrease of disease activity: mean disease activity was high (DAS28 [ 5.1) at the initiation of biological therapy, and physicians expected patients to achieve an average score near to the commonly used cut-off for low disease activity (DAS28 \ 3.2) after three months.
Mobility
Self-care
Usual activities Pain / discomfort
Physician
Patient
Common daily activities
Patient
Grip
Physician
Physician
Patient
Patient
Reach
Physician
Walking Hygiene
Physician
Patient
Physician
Physician
Patient
Patient
Eating
0%
Patient
Dressing Arising and grooming
Physician
Patient
Physician
10%
Physician
20%
0%
Patient
10%
Patient
20%
Physician
30%
50%
Patient
40%
60%
Physician
50%
70%
Patient
60%
Physician
70%
Rate of responses, %
Rate of responses, %
48.080 (21.823) NA
Anxiety / depression
EQ -5D dimensions Severe problem
Mild problem
No problem
Fig. 2 Estimated levels of health problems in the EQ-5D-3L domains for three months ahead by RA patients (N = 92) and treating rheumatologists
It is notable how similar the expected average scores on the HAQ-DI and EQ-5D were between patients and rheumatologists (Table 2). However, closer inspection of the scoring patterns showed differences on the underlying dimensions in both instruments. Figure 1 shows that on most dimensions of the HAQ-DI patients more often selected the two extreme scoring categories (‘unable to do’ and ‘without any difficulty’; 47.6 vs. 39.1 %, p \ 0.05) and rheumatologists selected the two middle scoring categories (‘with much difficulty’ and ‘with some difficulty’; 44.4 vs. 52.8 %, p \ 0.05). These differences were most prominent for the ‘Eating’ and ‘Common daily activities’ dimensions. Figure 2 shows that patients and rheumatologists also scored differently on the EQ-5D,
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M. Pe´ntek et al. Table 3 Comparison of expected scores at biological therapy initiation and RA patients’ measured values after three months (subsample with complete data on all relevant measures, N = 77)
Health measures
Baseline score (Visit 1)
Subjective expectations at 3 months (Visit 1)
Actual score after 3 months (Visit 2)
Difference between expected and actual scores (Visit 1–2)
1.442 (0.666)
0.644 (0.561)
0.957 (0.584)
-0.313 (0.509)*
NA
0.640 (0.493)
NA
-0.318 (0.645)*
HAQ-DIa Patients Rheumatologists EQ-5D scoreb Patients
0.356 (0.352)
0.744 (0.284)
0.629 (0.235)
0.115 (0.248)*
Rheumatologists
NA
0.750 (0.197)
NA
0.121 (0.280)* 1.727 (18.501)
EQ VASb * p \ 0.01 a
Higher score corresponds to worse status
b
Higher score corresponds to better status
Patients
48.400 (21.165)
65.650 (19.650)
63.920 (16.443)
Rheumatologists
NA
63.050 (17.539)
NA
-0.870 (19.426)
4.082 (1.231)
-0.257 (1.415)
Disease activity score (DAS28)a Rheumatologists
6.131 (0.896)
with rheumatologists slightly more often selecting the middle category, but not significantly so (‘mild problems’; 33 vs. 38 %, p = 0.178). In other words, RA patients and rheumatologists expect a similar substantial improvement in patients’ health after tkhree months due to biological treatment, but the underlying patterns of expected improvements differ. Comparison of subjective expectations and actual health at three months At follow-up (Visit 2), 85 (92 %) patients of the initial sample (N = 92) continued using their initial biologic drug and dosage, three (3 %) patients had switched their initial biological drug to another due to an adverse event, one (1 %) had dosage increased due to inefficacy and three (3 %) patients had to stop biological treatment. Proportions of treatment continuations of the subsample of 77 patients completing both questionnaires (at Visit 1 and Visit 2) were similar to those in the total sample (no change: 69 (90 %); dosage increase due to inefficacy: two (3 %); switch due to adverse event: two (3 %); switch due to inefficacy: one (1 %); stop of biological treatment and: three (4 %) patients). Comparisons of initial expectations and actual health scores after three months are presented on Table 3. Also in this subsample (N = 77), both rheumatologists and patients expected significant improvement of health with biological therapy on all outcomes and, indeed, significant improvements were achieved. Comparison of baseline estimations and follow-up scores indicates that both rheumatologists and patients significantly overestimated the improvement of functional and general health status on the HAQ-DI and EQ-5D, but that their estimations on the EQ-VAS were fairly accurate (p = 0.416 and p = 0.695,
123
3.825 (0.867)
0,9 0,8 0,7 0,6
EQ -5D score , mean
NA not applicable
0,5 0,4 0,3 0,2 0,1 0
-0,1
60
70
80
90
Age, years Subjective health expectations for specific ages: a web -based population survey (Péntek et al, 2012)
Subjective health expectations for specific ages: RA patients initiating first biological therapy
Actual health status of the general population* (Szende et al, 2003)
Fig. 3 RA patients’ subjective expectations on health status for specific ages (60, 70, 80 and 90) compared to results of a previous population survey in Hungary and the actual health status of the general population [14, 21]. Asterisks indicates mean EQ-5D scores of age groups 55–64, 65–74, 75–84 and C85 years are presented
respectively). Rheumatologists’ estimates on the DAS28 were also not statistically different from actual values (p = 0.115).
Subjective health expectations at biological therapy
Subjective expectations of health at older age
Discussion
RA patients’ (N = 92) subjective expectations regarding their health status in the further future are presented in Fig. 3. It is notable that RA patients expect a sharp decrease of their health with age, from a health-related quality of life score of 0.436 at age 60 to -0.019 at age 90, which is just below the value of the state ‘dead’. These figures are considerably lower than those previously observed among the general population in Hungary [21] or expected by members of the general public in Hungary [14].
This explorative study aimed to investigate subjective expectations of RA patients and their physicians regarding the three months effectiveness of treatment with biologicals as well as the subjective expectations of RA patients regarding their general future health and longevity. Since such expectations may influence treatment decisions, treatment evaluation and treatment persistence, exploring them is important. A unique feature of this study is that we were also able to compare expected gains with actual gains after three months. We assessed expected health gains and future health in a sample of Hungarian RA patients and their rheumatologists. Our results indicate that RA patients, who are typically in poor health when starting treatment with biologicals, have high expectations of treatment with biologicals. They expected significant improvements within three months. This was also observed for their physicians. Expecting an improvement is not unrealistic, since HAQDI decreases due to treatment with biologicals have indeed been observed in clinical trials (albeit often measured after six months or one year) [26]. The degree of expected health gain was relatively high, however, both for patients and physicians. Our follow-up data indicated that the expected (sizeable) improvements in HAQ-DI and EQ-5D scores were not observed after three months. Expectations regarding EQ VAS scores and DAS28 (for physicians) proved to be more accurate. Educational level and age appeared to be associated with these expectations. RA patients moreover expected relatively poor health states at older ages as well as relatively short life duration. These findings are important, since overoptimistic expectations as observed here may cause patients and their physicians to be disappointed with the actual improvements in health. Similarly, slower improvement than anticipated or more initial side-effects may cause patients (and physicians) to undervalue the achieved improvements and to discontinue treatment. Before discussing some findings and implications in more detail, some limitations of our study need noting. First, our sample stemmed from a single country and was relatively small. Therefore, our results are not necessarily representative for Hungarian RA patients starting treatment with biologicals, nor for their rheumatologists, and the results cannot be generalised to other countries. Moreover, we only had a small subsample of male RA patients, which emphasises the need for caution in interpreting results and generalising results. Although we feel that the current sample was appropriate for our explorative purposes, we encourage new studies in other (and larger) samples, also in other countries. Second, a unique feature of our study was its longitudinal design which allowed comparing
Subjective expectations of length of life Altogether 86 patients (females: 76, males 10; response rate 93 %) completed the question regarding expected longevity. RA patients on average expected to live to the age of 78.1 (SD 11.2) years (females 78.7, SD 10.7 vs. males 73.7, SD 14.3; p = 0.187). This is a bit lower than the expectation observed in the Hungarian general public (total sample: 79.6, SD 10.8; females 80.3, SD 10.1; males 79.3, SD 11.2, see Pe´ntek et al., In press) [14]. The gender-matched and age-matched statistical life expectancy of the general population in Hungary is slightly higher than this expectation (mean 79.2, SD 2.9; females 79.9, SD 2.0; males 73.6, SD 2.7), but not significantly so. Determinants of RA patients’ subjective expectations Stepwise linear regression analysis showed that patients’ expectations about the effect of the treatment were associated with a limited number of characteristics. Expected HAQ-DI scores after three months were positively associated with age (p \ 0.05) and negatively with educational level (p \ 0.00). Expected EQ-5D scores after three months were negatively associated with age (p \ 0.05) and positively with educational level (p \ 0.01). In other words, older and lower educated RA patients expected to have a worse functional and health status three months after biological therapy initiation than their younger and higher educated counterparts. In addition, female patients expected higher EQ-5D scores after three months than male patients (p \ .01). The results for the accuracy of those expectations after three months, gave ambiguous results. Linear regression of the difference between expected scores at Visit 1 and actual scores at Visit 2 were positively associated with education level for HAQ (p \ 0.05), while these were negatively associated with educational level (p \ 0.01) and positively with employment status (p \ 0.05) for EQ-5D.
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M. Pe´ntek et al.
expectations with actual health gains due to treatment. We used one follow-up after three months. Obviously, using a longer follow-up period or more follow-up moments might have yielded other results. We encourage new studies to investigate this further. Third, the similarities between physicians’ and patients’ expectations were, when considering average scores, striking. One might expect patients’ expectations to have been influenced by the information provided by their rheumatologists, which in turn may have been coloured by their expectations. The similarities between the average expectations for EQ-5D and HAQ-DI scores seem to support this hypothesis. However, patients’ and rheumatologists’ expectations were different at the level of the health domains, i.e., the type of activities and health dimensions they expected to improve with the therapy. Hence, the exact source of expectation formation remains unclear and seems a fruitful area for future research. Moreover, the sometimes subtle differences in expectations between patients and physicians deserve attention and highlight the importance of involving expectations in discussions between patients and physicians. Fourth, the instruments and methods for measuring expectations are not yet well developed. Here, we drew as much as possible on previously used methods [13, 14]. We have no indication that patients or rheumatologists considered the questionnaire to be difficult to comprehend or complete. Still, it cannot be ruled out that other ways of investigating expectations or the use of other instruments, would have resulted in different results. Notwithstanding these limitations, we feel that the findings of this study convey some important messages. Our results indicate that RA patients and their physicians appear to have (in some ways unrealistically) high expectations of treatment with biological treatments. The subjective expectations of patients may serve as an important reference point influencing patients’ disease and treatment assessment and compliance. Hence, the fact that patients and physicians are, in general, overly optimistic in their expectations regarding the treatment effects of biologicals (measured with EQ-5D and HAQ-DI scores) could imply that the actual improvements could be judged less favourable than had been the case if patients (and physicians) had lower expectations. It would be interesting to assess in future research how patients and physicians evaluate the gap between expectations and realisations. It was interesting to observe that the EQ VAS (patients) and DAS28 (rheumatologists) scores were more accurate when compared to actual treatment effects after three months than the EQ-5D and HAQ-DI scores. One potential cause of the more accurate estimation with these former tools might be that patients might be more familiar with VAS scores (since self-assessment on a VAS is part of regular RA care) and rheumatologists are more
123
experienced with the DAS28 than with the other two quality of life questionnaires. Furthermore, estimating a single score might result in more accurate estimations than assessing expected improvement on a disaggregate descriptive questionnaire. The lack of validated questionnaires to assess expectations indicates an important area for future research. It does seem that this field is developing, underlining its importance. Ferrari and colleagues [27] for instance used the HAQ-DI in an imaginary scenario to assess university students’ expectations of disability if they had RA. Hofman et al. [28] have recently presented two initial phases of the development of a patient-generated treatment expectancy measure. Some items of this questionnaire assess health domains similar to those measured in the EQ-5D, HAQ-DI and DAS28 (e.g., mobility, pain, everyday activities, swelling of the joints). However, it includes additional aspects that RA patients considered relevant (e.g., visible signs of RA, joint damage, fatigue or reduce the likelihood of surgery). While such exploration of patients’ expectations undoubtedly yields richer insights, our approach was chosen in order to be able to compare expected and actual outcomes. Hence, we stayed close to well accepted measurement methods in the field of RA and our results show that this approach is feasible. The validity of our approach can be studied further in future studies. An interesting aspect of our study was the additional focus on long term health expectations among RA patients. In contrast to the (overly) optimistic expectations regarding the effectiveness of the treatment with biologicals, RA patients do expect a fairly sharp decline in health over time. Current health and functioning (EQ-5D and HAQ-DI) were found to be clearly related to long term health expectations (for ages 60, 70, 80 and 90). An EQ-5D score of 0.436 was expected for the age of 60 and further decline was expected for older ages. These figures were compared to those obtained in a sample of the Hungarian general public, using the same methodology [14] (see Fig. 3). While the declining trend in future quality of life and low scores for old ages was also observed there, but primarily for the ages 80 and 90, the expectations of RA patients were clearly lower than observed quality of life in Hungary for all older age groups. RA patients’ expectations were lower than those of the general public for all observed future ages. This difference was also observed when only considering the subsample of 45–54 years old from the general public sample, which better resemble the average age of the RA patients (N = 1,200; expected mean scores for ages 60, 70, 80 and 90: 0.76, 0.59, 0.32 and 0.04). Future research could focus on the quality of life expectations of RA patients for the years before the age of 60, also in relation to the expected treatment effects of biologicals. In depth (qualitative) analysis of the apparent discrepancy between expectations regarding future quality and length of life and
Subjective health expectations at biological therapy
treatment effects is encouraged as well. One potential explanation for the current findings is that RA patients might worry about or even fear the idea of growing old with RA and may expect the biologicals to only (effectively) postpone the ‘inevitable’ decline in quality of life. Given that real life data regarding the long term effects of biological treatments on quality of life are becoming available from various registries [29], the accuracy of expectations of RA patients can be further evaluated. Longer term health expectations could be explicitly discussed between patients and rheumatologists at initiation of and during treatment with biologicals. Deriving subjective life expectancy of RA patients also yielded some interesting results. RA patients with persistent high disease activity have an increased risk of mortality. Hence, a relatively low subjective life expectancy could be expected. However, it must be noted that observational studies confirmed that biological drugs may reduce premature mortality in RA patients when compared to other treatment regimens [30]. In this study, RA patients’ expectations regarding length of life were just below the gender and age-matched statistical life-expectancy of the Hungarian population (mean -1.1 years), but this difference was not statistically significant. While this indicates that RA patients may not have adjusted their life expectancy, this may not be fully accurate, since on average, people from the Hungarian general public appear to (considerably) overestimate their life expectancy, i.e., women 1.6 years and men 8.2 years [14], which was similar to the pattern found in The Netherlands [13]. Only considering the subsample of 45–54 years old in the Hungarian general public sample indicated an overestimation of 0.3 years for women and 7.7 years for men [14]. In the current study, such a pronounced gender difference was not observed, but our sample of men was too small to draw any firm conclusions on this matter. In general, it seems that RA patients have somewhat lower longevity expectations than their counterparts in the general public and their statistical life-expectancy. Future research could investigate these expectations further, including the question whether RA patients are aware of their increased mortality risk and how they expect biologicals to affect this. Regression analysis demonstrated that older and lower educated patients expected a worse health status after three months after initiation of biological treatment. However, for more insightful analysis of the determinants of expectations and their accuracy a larger sample is necessary in future studies. Further potential explanatory factors of subjective expectations, such as satisfaction with life in general and the health care system in particular, riskseeking or risk-averse health behaviour and access to health care are worth studying in the future.
In conclusion, we feel that this explorative study has emphasised the importance and feasibility of investigating subjective expectations regarding treatment effects and future length and quality of life in patients suffering from diseases such as RA. More research in this area is encouraged, because these expectations may influence treatment compliance, persistence and evaluation, as well as more general life-style choices, health spending and discounting. Better understanding of expectations of patients and physicians, in general regarding future health, and in particular regarding treatment effectiveness, remains an important objective. This paper hopes to have contributed to that goal. Acknowledgments Authors are grateful to the patients who participated in the survey and the following colleagues for assisting with the local data collection: Ange´la Fu¨lo¨p, Pa´l Ge´her, Ilona Ujfalussy and Magdolna Tandari (Budapest); Zolta´n Szekanecz, No´ra Bodna´r, Gabriella Sz} ucs, Szilvia Szamosi and Andrea Va´ncsa (Debrecen); Pe´ter Keszthelyi, Hajnalka Kova´cs, Kla´ra Abruda´n and Zsuzsa ´ gnes Edit To´th, Gyo¨ngyi Za´vada (Gyula); Ferenc Szanyo´ (Gy} or); A Bo¨jte, Annama´ria Eiben and Gre´ta Sterba (Kistarcsa); La´szlo´ Tama´si, ´ gnes Flo´ria´n and Katalin Luka´cs (Miskolc); Tibor Katalin Fazekas, A Varju´, Zita Szabo´, Erzse´bet Encs and Andrea Tisza (Nyı´regyha´za); La´szlo´ Kova´cs, Attila Balogh and Daniella Hullo´ (Szeged); Attila Kova´cs, Bea´ta Baksay, Judit Bı´ro´ and Katalin Ga´csi (Szolnok); Lilla Na´fra´di (Szombathely); La´szlo´ Czirja´k, Do´ra Niedermayer and Cecı´lia Varju´ (Pe´cs). The survey was supported by an independent grant from the Centre for Public Affairs Studies Foundation and HTA Co.
Appendix Questionnaire used in the survey: expected health problems at ages 60, 70, 80 and 90 were asked applying the statements of the EQ-5D.
I think at age 60 I will have… (Please mark your response) a.
No
Some
Major
Problems with walking about
b.
No
Some
Major
Problems with washing or dressing
c.
No
Some
Major
Problems with performing usual activities
d.
No
Some
Severe
Pain or discomfort
e.
No
Some
Severe
Anxiety or depression
Ages 70, 80 and 90 were asked in a same construct
References 1. Boonen, A., Severens, J.L.: The burden of illness of rheumatoid arthritis. Clin. Rheumatol. 30(Suppl 1), S3–S8 (2011) 2. Furneri, G., Mantovani, L.G., Belisari, A., Mosca, M., Cristiani, M., Bellelli, S., Cortesi, P.A., Turchetti, G.: Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. Clin. Exp. Rheumatol. 30(4 Suppl 73), S72–S84 (2012)
123
M. Pe´ntek et al. 3. Upchurch, K.S., Kay, J.: Evolution of treatment for rheumatoid arthritis. Rheumatology (Oxford) 51(Suppl 6), vi28–vi36 (2012) 4. Smolen, J.S., Landewe, R., Breedveld, F.C., Buch, M., Burmester, G., Dougados, M., Emery, P., Gaujoux-Viala, C., Gossec, L., Nam, J., Ramiro, S., Winthrop, K., de Wit, M., Aletaha, D., Betteridge, N., Bijlsma, J.W., Boers, M., Buttgereit, F., Combe, B., Cutolo, M., Damjanov, N., Hazes, J.M., Kouloumas, M., Kvien, T.K., Mariette, X., Pavelka, K., van Riel, P.L., RubbertRoth, A., Scholte-Voshaar, M., Scott, D.L., Sokka-Isler, T., Wong, J.B., van der Heijde, D.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann. Rheum. Dis. 73(3), 492–509 (2014) 5. Kobelt, G., Jonsson, B.: The burden of rheumatoid arthritis and access to treatment: outcome and cost-utility of treatments. Eur J Health Econ 8(Suppl 2), 95–106 (2008) 6. Bendtsen, P., Akerlind, I., Hornquist, J.O.: Pharmacological intervention in older patients with rheumatoid arthritis. Quality of life aspects. Drugs Aging 7(5), 338–346 (1995) 7. Epstein, W.V.: Expectation bias in rheumatoid arthritis clinical trials. The anti-CD4 monoclonal antibody experience. Arthritis Rheum. 39(11), 1773–1780 (1996) 8. Kvien, T.K., Heiberg, T.: Patient perspective in outcome assessments–perceptions or something more? J. Rheumatol. 30(4), 873–876 (2003) 9. Simon, L.S.: The treatment of rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 18(4), 507–538 (2004) 10. Alcorn, N., Waite, L., Madhok, R.: Transforming the expectations of patients with rheumatoid arthritis? Rheumatology (Oxford) 49(7), 1211–1212 (2010) 11. van Vollenhoven, R.F.: Unresolved issues in biologic therapy for rheumatoid arthritis. Nat. Rev. Rheumatol. 7(4), 205–215 (2011) 12. Mirowsky, J.: Subjective life expectancy in the US: correspondence to actuarial estimates by age, sex and race. Soc. Sci. Med. 49(7), 967–979 (1999) 13. Brouwer, W.B., van Exel, N.J.: Expectations regarding length and health related quality of life: some empirical findings. Soc. Sci. Med. 61(5), 1083–1094 (2005) 14. Pentek, M., Brodszky, V., Gulacsi, A.L., Hajdu, O., van Exel, J., Brouwer, W., Gulacsi, L.: Subjective expectations regarding length and health-related quality of life in Hungary: results from an empirical investigation. Health Expect. (2012). doi:10.1111/j. 1369-7625.2012.00797.x 15. Marshall, N.J., Wilson, G., Lapworth, K., Kay, L.J.: Patients’ perceptions of treatment with anti-TNF therapy for rheumatoid arthritis: a qualitative study. Rheumatology (Oxford) 43(8), 1034–1038 (2004) 16. Funahashi, K., Matsubara, T.: What RA patients expect of their treatment–discussion over the result of our survey. Clin. Rheumatol. 31(11), 1559–1566 (2012) 17. Bergsten, U., Bergman, S., Fridlund, B., Arvidsson, B.: Delivering knowledge and advice: healthcare providers’ experiences of
123
18.
19.
20.
21. 22.
23.
24.
25.
26.
27.
28.
29.
30.
their interaction with patients’ management of rheumatoid arthritis. Int. J. Qual. Stud. Health Well-being 6(4) (2011) Buitinga, L., Braakman-Jansen, L.M., Taal, E., van de Laar, M.A.: Future expectations and worst-case future scenarios of patients with rheumatoid arthritis: a focus group study. Musculoskelet. Care 10(4), 240–247 (2012) Bruce, B., Fries, J.F.: The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual. Life Outcomes 1, 20 (2003) EuroQoL-Group: EuroQol: a new facility for the measurement of health-related quality of life. Health Policy 16(3), 199–208 (1990) Szende, A., Nemeth, R.: Health-related quality of life of the Hungarian population. Orv. Hetil. 144(34), 1667–1674 (2003) Lillegraven, S., Kvien, T.K.: Measuring disability and quality of life in established rheumatoid arthritis. Best Pract. Res. Clin. Rheumatol. 21(5), 827–840 (2007) Anderson, J., Caplan, L., Yazdany, J., Robbins, M.L., Neogi, T., Michaud, K., Saag, K.G., O’Dell, J.R., Kazi, S.: Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis. Care Res. (Hoboken) 64(5), 640–647 (2012) Hobbs, K.F., Cohen, M.D.: Rheumatoid arthritis disease measurement: a new old idea. Rheumatology (Oxford) 51(Suppl 6), vi21–vi27 (2012) Marra, C.A., Woolcott, J.C., Kopec, J.A., Shojania, K., Offer, R., Brazier, J.E., Esdaile, J.M., Anis, A.H.: A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis. Soc. Sci. Med. 60(7), 1571–1582 (2005) Schmitz, S., Adams, R., Walsh, C.D., Barry, M., FitzGerald, O.: A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach. Ann. Rheum. Dis. 71(2), 225–230 (2012) Ferrari, R., Russell, A.S.: Correlations between coping styles and symptom expectation for rheumatoid arthritis. Clin. Rheumatol. 29(12), 1445–1448 (2010) Hofmann, D., Ibrahim, F., Rose, D., Scott, D.L., Cope, A., Wykes, T., Lempp, H.: Expectations of new treatment in rheumatoid arthritis: developing a patient-generated questionnaire. Health Expect. (2013). doi:10.1111/hex.12073 Yoshida, K., Radner, H., Kavanaugh, A., Sung, Y.K., Bae, S.C., Kishimoto, M., Matsui, K., Okada, M., Tohma, S., Weinblatt, M.E., Solomon, D.H.: Use of data from multiple registries in studying biologic discontinuation: challenges and opportunities. Clin. Exp. Rheumatol. 31(4 Suppl 78), S28–S32 (2013) Listing, J., Kekow, J., Manger, B., Burmester, G.R., Pattloch, D., Zink, A., Strangfeld, A.: Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab. Ann. Rheum. Dis. (2013). doi:10. 1136/annrheumdis-2013-204021
