BJD
British Journal of Dermatology
T H E R A P E U T I CS
Satisfaction of treatment with biologics is high in psoriasis: results from the Bio-CAPTURE network* €umig,1 M.E. Otero,1 J. Zweegers,1 P.C.M. van de Kerkhof,1 J.M.P.A. van den Reek,1 P.P.M. van Lu 2 2 P.M. Ossenkoppele, M.D. Njoo, J.M. Mommers,3 M.I.A. Koetsier,4 W.P. Arnold,5 B.A.M. Sybrandy-Fleuren,6 A.L.A. Kuijpers,7 M.P.M. Andriessen,8 M.M.B. Seyger,1 W. Kievit9 and E.M.G.J. de Jong1 1
Department Department 3 Department 4 Department 5 Department 6 Department 7 Department 8 Department 2
of of of of of of of of
Dermatology and 9Department of Health Evidence, Radboud University Medical Centre, Nijmegen, the Netherlands Dermatology, Ziekenhuisgroep Twente, Almelo/Hengelo, the Netherlands Dermatology, St. Anna Ziekenhuis, Geldrop, the Netherlands Dermatology, Gelre Ziekenhuizen, Apeldoorn, the Netherlands Dermatology, Ziekenhuis Gelderse Vallei, Ede, the Netherlands Dermatology, Slingeland Ziekenhuis, Doetinchem, the Netherlands Dermatology, Maxima Medisch Centrum, Eindhoven/Veldhoven, the Netherlands Dermatology, Jeroen Bosch Ziekenhuis, Den Bosch, the Netherlands
Summary Correspondence Juul M.P.A. van den Reek. E-mail: [email protected]
Accepted for publication 27 January 2014
Funding sources This study was supported by the University Medical Centre St Radboud Foundation, which received funding for the project from Pfizer, Janssen and AbbVie. Pfizer, Janssen and AbbVie played no role in the design and execution of the study; in data collection, data management, data analysis and interpretation of the data; or manuscript preparation, review and approval.
Conflicts of interest See Appendix. *Plain language summary available online DOI 10.1111/bjd.12862
Background Although the effectiveness of biologics for psoriasis has been measured extensively with objective outcome measures, studies based on subjective, patient-reported outcome measures remain scarce. Objectives To investigate satisfaction with medication, as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) for biologics in daily practice psoriasis care in the first 6 months of treatment; and to identify possible differences in satisfaction with medication between patients experienced (biologics-experienced) and inexperienced (biologics-inexperienced) in the use of biologics. Methods TSQM baseline measurements were compared using measurements taken after 6 months, using the Wilcoxon signed-rank test for paired comparisons. Intention-to-treat with last observation carried forward (ITT with LOCF) and astreated analyses were performed. The difference between biologics-experienced and biologics-inexperienced patients for TSQM was analysed using ITT with LOCF. At 6 months, outcomes for biologics-experienced and biologics-inexperienced patients were compared using the Mann–Whitney U-test. Results One hundred and six patients were eligible for analysis, and treated with etanercept (n = 34), adalimumab (n = 49) or ustekinumab (n = 23). Fifty-four per cent of patients were biologics-inexperienced. A statistically significant improvement was seen in all domains of the TSQM (‘effectiveness’, ‘side-effects’, ‘convenience’ and ‘global satisfaction’) by comparison of months 3 or 6 with baseline (all P ≤ 002). After 6 months, biologics-inexperienced patients scored better on the ‘global satisfaction’ domain than biologics-experienced patients (P < 001). Conclusions We provide a prospective, longitudinal analysis of TSQM for biologics in daily practice psoriasis care. High satisfaction rates were achieved. The ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement.
What’s already known about this topic?
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Maximum satisfaction with medication is thought to be positively related to adherence, health-related quality of life and patients’ preferences.
British Journal of Dermatology (2014) 170, pp1158–1165
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Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1159
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As shown in cross-sectional research, patients’ dissatisfaction with treatment plays an important role in psoriasis. Those receiving biologics are the most satisfied with treatment among patients with psoriasis. In an open-label extension trial with etanercept, significant improvement in the ‘global satisfaction’, ‘effectiveness’ and ‘convenience’ domains was achieved after 3 months of treatment.
What does this study add?
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A prospective, longitudinal study on satisfaction with etanercept, adalimumab and ustekinumab for patients with psoriasis in daily practice. Significantly improved satisfaction rates (using the Treatment Satisfaction Questionnaire for Medication) were achieved after 3 and 6 months. As reported by the patients, the ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement. After 6 months, biologics-inexperienced patients scored significantly better on the ‘global satisfaction’ domain than experienced patients.
In recent years, effective targeted biological treatments have become available for the treatment of patients with moderateto-severe psoriasis. The effectiveness of these agents has been measured extensively with objective outcome measures, such as Psoriasis Area and Severity Index scores.1–3 However, in the evaluation of treatments, patient reported outcomes (PROs) are important as well.4–6 An under-reported PRO in the field of psoriasis treatment is ‘satisfaction with medication’. The Treatment Satisfaction Questionnaire for Medication (TSQM) has been developed to gauge satisfaction with medication for different indications.7 This generic questionnaire provides insight into different domains of treatment satisfaction.7 In treating patients with psoriasis, maximum satisfaction with medication should be aimed for as it is thought to be related positively to adherence, health-related quality of life and patients’ preferences.8–11 It also provides insight into what should be improved in the drug itself.8–10 Vender et al. provided an analysis, based on the TSQM, of etanercept in an open-label trial, and found significant improvement in the ‘global satisfaction’, ‘effectiveness’ and ‘convenience’ domains after 3 months of treatment.12 A cross-sectional investigation of treatment satisfaction using the TSQM in a daily practice cohort treated with biologics was carried out by Driessen et al.13 Recently, Callis Duffin et al.14 analysed the TSQM in a cross-sectional study comparing different antipsoriatic treatments. Our study provides a prospective, longitudinal analysis of patients in daily practice starting or switching biologics. The primary objective of this prospective study was to investigate satisfaction with medication, as measured by the TSQM (version II): for biological therapies in daily practice psoriasis care in the first 6 months of treatment. The secondary objective was to identify possible differences in satisfaction with medication between patients experienced and inexperienced in the use of biologics. © 2014 British Association of Dermatologists
Materials and methods The Bio-CAPTURE database Data were extracted from a prospective registry (BioCAPTURE: Continuous Assessment of Psoriasis Treatment Use Registry with Biologics) containing daily practice data from all patients with psoriasis treated with biologics. The registry contains data on effectiveness, PROs and pharmacovigilance. Founded in 2005, it is based in the Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands. Eight regional nonacademic centres have participated in this registry since 2011, and all consecutive patients treated with biologics are enrolled in it. Patients were treated, according to the opinion of the treating dermatologist, with etanercept, adalimumab, infliximab or ustekinumab. Preferably, patients were treated according to the regimens recommended by the European Medicines Agency label, and European and Dutch national guidelines for treatment with biologics.15–17 If necessary, dosage adjustments, interval changes and/or combination therapy with topical or other antipsoriatic systemic therapies were applied. The registry was approved by our medical ethics committee. According to Dutch law, informed consent was not mandatory for this noninterventional study; however, it is obtained from every newly included patient. Treatment satisfaction questionnaire for medication From January 2010 to July 2013, all patients starting a biologic for the first time or switching to another biologic were asked to fill out a TSQM (version II). This questionnaire is included in the Bio-CAPTURE study. In this time frame, etanercept, adalimumab and ustekinumab were equally available in daily practice. Patients received questionnaires at British Journal of Dermatology (2014) 170, pp1158–1165
1160 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
baseline and after 3 and 6 months, or until the moment of discontinuation (when patients stopped before 6 months of therapy). The TSQM (version II) is a generic, multilinguistically validated questionnaire developed for different patients and medications, and is therefore applicable to our patient group. The TSQM covers four important domains of satisfaction with medication: efficacy, convenience, general satisfaction and side-effects. The scores for the domains range from 0 (extremely dissatisfied) to 100 (extremely satisfied).7 The questionnaire refers to the time frame 2–3 weeks prior to completion of the questionnaire. Therefore, the baseline measures provide information about the last treatment used before the initiation of the biologic. Data collection and extraction At every visit, all data on effectiveness and safety (adverse events) were collected on a standardized case report form (CRF) by a trained physician or nurse. The data manager entered the data into the Bio-CAPTURE database, and checked the source documents for incomplete or incorrect data on the CRF. Every 3 months, patients received TSQM questionnaires by mail. After retrieving completed TSQM questionnaires, scores were entered into the Bio-CAPTURE database. Data were extracted from the database and imported into SPSS Statistics 20 (IBM, Armonk, NY, U.S.A) for further analysis. Statistical analysis TSQM data on etanercept, adalimumab and ustekinumab were analysed. Descriptive statistics [means SD or medians (range)] were used to summarize TSQM data. The four TSQM subdomains were analysed separately. To explore the additional effects of biologics on each domain, baseline measurements were compared with measurements taken after 3 and 6 months using a Wilcoxon signed rank test. In order to detect possible bias due to missing values or selection, two analyses were performed: (i) an intention-totreat (ITT) with last observation carried forward (ITT with LOCF) analysis, which represented the most conservative approach; and (ii) an as-treated analysis, which represented the most positive approach.18 In the ITT with LOCF analysis, missing values for month 3, were imputed by baseline values; missing values for month 6 were imputed with month 3 values. To investigate the influence of prior experiences with biological treatments on TSQM, patients were classified as ‘biologics-experienced’ (prior treatment with biologics) or ‘biologics-inexperienced’ (no prior treatment with biologics). Descriptive statistics were summarized, and differences in the main characteristics for biologics-experienced and biologicsinexperienced patients were tested. Categorical variables were compared using Pearson’s v2-test or Fisher’s exact test. Continuous variables with a parametric distribution were analysed using an independent t-test; continuous variables with a nonparametric distribution were analysed using a Mann–Whitney U-test (ITT with LOCF). At month 6, the outcomes of biBritish Journal of Dermatology (2014) 170, pp1158–1165
ologics-experienced and biologics-inexperienced patients were compared directly using the Mann–Whitney U-test to identify possible differences in satisfaction at this end point. Additionally, other factors that could theoretically influence satisfaction with medication were analysed using a Mann–Whitney U-test for month 6 outcomes (ITT with LOCF). These variables were age, disease duration and sex. Patients aged < 40 years and ≥ 40 years were compared. We chose this cut-off point in order to take into account important age-specific issues, such as studying, first working years and family planning (< 40 years) vs. late working years with established careers and a higher prevalence of comorbidities (≥ 40 years). With regard to disease duration, we compared patients with a relatively short disease duration (< 10 years) with patients with more established psoriasis (≥ 10 years). A P-value < 005 was considered significant in all analyses. SPSS Statistics 20 (IBM) was used to perform the analyses.
Results Patient and treatment characteristics One hundred and seventeen unique patients were included in this study. Eleven patients were excluded: nine patients had less than 6 months follow up < 6 months and two were lost to follow-up. Therefore, 106 patients using adalimumab (n = 49, 46%), etanercept (n = 34, 32%) or ustekinumab (n = 23, 22%) were eligible for analysis. Patient characteristics are presented in Table 1. Little more than half of the patients were biologics-inexperienced (n = 57, 54%). Baseline median scores for TSQM were 50% (range 0–1000) for ‘effectiveness’, 92% (range 83–1000) for ‘side-effects’, 67% (range 0–1000) for ‘convenience’ and 58% (range 0–1000) for ‘global satisfaction’. Baseline measures represent satisfaction with medication in the period directly preceding the start of the studied biologic. The most frequently used agents in this period were methotrexate monotherapy (n = 27, 27%) and etanercept monotherTable 1 Patient characteristics (n = 106) General characteristics Sex (male) Age (years), mean SD Duration of disease (years), median (range)a Experience with prior biologics Experienced (non-naive) Inexperienced (naive) Status at time of analysis Active user of biologic for > 4 months Discontinued biologic < 4 months Hospital type Academic Nonacademic
62 (585) 482 123 204 (24–536) 49 (462) 57 (538) 99 (934) 7 (66) 71 (670) 35 (330)
Data are n (%) unless otherwise indicated. aData missing from three patients at the time of entry into the study.
© 2014 British Association of Dermatologists
Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1161 Table 2 Systemic antipsoriatic treatment in the 4 weeks prior to initiation of the study biologic (n = 101)a Treatment
n (%)
No systemic antipsoriatic Methotrexate Etanercept Ciclosporin Adalimumab Furamic acid esters UVB Acitretin Adalimumab + methotrexate Dithranol Infliximab Ustekinumab
30 (297) 27 (267) 15 (149) 9 (89) 8 (79) 4 (40) 2 (20) 2 (20) 1 (10) 1 (10) 1 (10) 1 (10)
UVB, ultraviolet B; aFive cases unknown.
apy (n = 15, 15%). Thirty patients (30%) were not receiving systemic antipsoriatic therapy in this time frame. Other therapies used in this period are outlined in Table 2. Satisfaction with treatment after 3 and 6 months Using ITT with LOCF, median scores at month 3 were 67% for the ‘effectiveness’, 100% for the ‘side-effects’, 67% for the ‘convenience’ and 75% for the ‘global satisfaction’ domains. At month 6, the median scores were 67% for ‘effectiveness’, 100% for ‘side-effects’, 78% for ‘convenience’ and 83% for ‘global satisfaction’. As can be seen from these scores, the ‘effectiveness’ and ‘convenience’ domains show the most room for improvement at month 6. On all domains, a statistically significant improvement was seen by comparing subsequent measurements (months 3 and 6) with baseline (all P ≤ 002, paired Wilcoxon signed-rank test) (Fig. 1). Comparable results were seen in the as-treated analysis: all domains showed statistically significant improvement when comparing subsequent measurements (months 3 and 6) with the baseline (all P ≤ 002, paired Wilcoxon signed-rank test) (Fig. 2).
Satisfaction with treatment for biologics-experienced and biologics-inexperienced patients Table 3 shows the patient and treatment characteristics of biologics-experienced and biologics-inexperienced patients. Age, sex and body mass index were distributed equally among groups. Biologics-experienced patients used adalimumab more frequently, whereas biologics-inexperienced patients used etanercept more frequently. More biologics-inexperienced patients were treated in a nonacademic centre. Disease duration was longer among biologics-experienced patients. The TSQM responses of both biologics-experienced and biologicsinexperienced patients were analysed (ITT with LOCF): both groups showed statistically significant improvements in the ‘efficacy’, ‘convenience’ and ‘global satisfaction’ domains (all P < 005, paired Wilcoxon signed-rank test) after 3 and after 6 months compared with baseline. Biologics-inexperienced patients achieved a statistically significant improvement (P < 001) in the ‘side-effects’ domain after 3 and after 6 months compared with baseline. In contrast, no statistically significant difference was achieved in this domain by biologics-experienced patients (P = 080 and P = 030 after 3 and 6 months, respectively). To compare directly month 6 outcomes for biologics-experienced vs. biologics-inexperienced patients, a Mann–Whitney Utest was carried out (ITT with LOCF). This analysis revealed no statistically significant differences between the groups in the ‘effectiveness’ (P = 014), ‘side-effects’ (P = 028) and ‘convenience’ (P = 063) domains. However, in the ‘global satisfaction’ domain, significantly better outcomes were measured for biologics-inexperienced patients (P < 001) (Fig. 3). Satisfaction with treatment with regard to age, disease duration and sex The 6-month TSQM responses of patients aged < 40 years (n = 25) and ≥ 40 years (n = 81) were compared. Using a Mann–Whitney U-test, no statistically significant differences in the end point measures were found between groups in the ‘effectiveness’ (P = 089), ‘side-effects’ (P = 060), ‘convenience’ (P = 005) or ‘global satisfaction’ (P = 100) domains.
Fig 1. Treatment Satisfaction Questionnaire for Medication (TSQM) measures for patients with psoriasis treated with biologics (intention-to-treat with last observation carried forward analysis). Whiskers represent 10–90th percentiles. *Statistically significant improvement on Wilcoxon signed-rank test compared with baseline measurements. © 2014 British Association of Dermatologists
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1162 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
Fig 2. Treatment Satisfaction Questionnaire for Medication (TSQM) measures for psoriasis patients treated with biologics (as-treated analysis). Whiskers represent 10–90th percentiles. *Statistically significant improvement on Wilcoxon signed-rank test compared with baseline measurements. Table 3 Patient and treatment characteristics of biologics-experienced and biologics-inexperienced patients (n = 106) Not experienced (n = 57) Sex (male) Age (years), mean SD Duration of disease (years), mean SD Body mass index, median (range)/ mean SD Diabetes Treatment Adalimumab Etanercept Ustekinumab Hospital type Academic Nonacademic
Experienced (n = 49)
P-valuea b
33 (58) 479 126
29 (59) 486 121
089 078c
191 117d
252 128e
001c
272 (186–532)f
292 54g
020h
3 (5)i
7 (14)
019j
24 (42) 24 (42) 9 (16)
25 (51) 10 (20) 14 (29)
– – 004b
32 (56) 25 (44)
39 (80) 10 (20)
– 001b
Data are n (%) unless otherwise indicated. aBased on the difference between naive and non-naive patients. bPearson’s v2-test. c Independent t-test. dMissing the data of one patient. eMissing the data of two patients. fMissing the data of 12 patients. gMissing the data of 13 patients. hMann–Whitney U-test. iMissing the data of two patients. jFisher’s exact test.
The 6-month TSQM responses of patients with a relatively short disease duration (< 10 years, n = 17) vs. patients with more established psoriasis (≥ 10 years, n = 86) were compared. This comparison revealed a statistically significant difference in the ‘convenience’ domain in favour of patients with a longer disease duration (≥ 10 years) (P = 0.04), no statistically significant difference between groups for the ‘effectiveness’ (P = 087), ‘side effects’ (P = 050), and ‘global satisfaction’ (P = 054) domains was seen at month 6 (MannWhitney U test). No statistically significant difference between men (n = 62) and women (n = 44) was seen at month 6 for all TSQM domains: ‘effectiveness’ (P = 012), ‘side-effects’ (P = 047), British Journal of Dermatology (2014) 170, pp1158–1165
‘convenience’ (P = 054) and ‘global satisfaction’ (P = 046) (Mann-Whitney U test).
Discussion For the total group of patients treated with adalimumb, etanercept or ustekinumab, a statistical significant improvement was seen on all domains of TSQM comparing baseline with month 3 and 6 measures. Both biologics-experienced and biologics-inexperienced patients showed significant improvements in most domains of the TSQM. Biologicsinexperienced patients scored significantly better in the ‘global satisfaction’ domain compared with biologics-experienced patients after 6 months of treatment. Driessen et al.13 cross-sectionally investigated treatment satisfaction in a biologics-treated daily practice cohort, and found the highest scores in the ‘side-effects’ (91%) domain, followed by the ‘convenience’ (80%), ‘global satisfaction’ (78%) and ‘effectiveness’ (71%) domains. In an open-label study, Vender et al.12 measured, using the TSQM, treatment satisfaction with etanercept in psoriasis over 1 year. Over time, a significant improvement was seen in all domains, with the exception of the ‘side-effects’ domain. Our study provides an analysis of satisfaction with medication for three different biologics (adalimumab, etanercept and ustekinumab) instead of an analysis on etanercept alone. In addition, our study has a prospective and longitudinal study design. It is conceivable that satisfaction rates in patients who have received prior biologics could be influenced by former experiences, for example with effectiveness, side-effects or practical issues with other drugs. However, in patients with rheumatoid arthritis (RA), the baseline level of treatment satisfaction with different medications was not different between patients experienced and naive for antitumour necrosis factora agents.19 Our findings correspond with the results obtained in this RA study: we found no differences between baseline scores for TSQM for biologics-experienced and biologicsinexperienced patients (data not shown). Moreover, we found that both groups improved significantly in all domains of the TSQM in the first 6 months. The only exception was that biologics-experienced patients achieved no significant © 2014 British Association of Dermatologists
Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1163
Effecveness
Side-effects
Convenience
Global sasfacon
Fig 3. TSQM measures for biologics-experienced and biologics-inexperienced patients. Each figure shows medians with interquartile ranges (whiskers). Asterisks represent a significant improvement (P < 005) compared with baseline for the specific Treatment Satisfaction Questionnaire for Medication (TSQM) domain. Colour of asterisks corresponds with colour of lines.
improvement in the ‘side-effects’ domain. This finding was due to a ceiling effect: this subgroup of patients started with a (maximum) median score of 100% at baseline, which did not change after 3 or 6 months. When comparing the absolute scores directly between biologics-experienced and biologics-inexperienced patients after 6 months, significantly higher scores were seen in biologics-inexperienced patients in the ‘global satisfaction’ domain (P < 001). A possible explanation for this could be that, over time, experienced patients have become more used to the positive effects of biologics. Patients with a longer disease duration (≥ 10 years) scored significantly better in the ‘convenience’ domain than patients with a shorter disease duration (< 10 years). This could be explained by their long treatment history and experiences, which make them more easily accustomed to new treatments. © 2014 British Association of Dermatologists
In general, patients’ dissatisfaction with treatment plays an important role in the field of psoriasis. Although patients treated with biologics show the highest satisfaction, there is still room for improvement, as shown in cross-sectional research.13,14,20–22 The National Psoriasis Foundation found that 43% of patients with severe psoriasis (self-reported body surface area > 10%) were dissatisfied with their treatment.20 A survey by van Cranenburgh et al.22 revealed that patients with psoriasis rated ‘treatment effectiveness’ as the most important issue related to treatment satisfaction. It is therefore important to realize that we found this to be the factor with the most ‘room for improvement’. Our results correspond with the outcomes of Vender et al.12 and Driessen et al.,13 who also found the most room for improvement to be in the ‘effectiveness’ domain. This indicates that we should focus on ways to improve satisfaction with effectiveness when prescribing treatBritish Journal of Dermatology (2014) 170, pp1158–1165
1164 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
ment with biologics in daily practice. These results suggest that the development of treatments with higher efficacy is still needed in order to provide a solution for this unmet medical need. In addition, satisfaction with the effectiveness of a drug could also rely on other factors, such as expectations of effectiveness. A limitation of our study was that head-to-head comparisons between agents were not opportune owing to group size. Furthermore, responder bias is an issue in questionnaire research, and we had to deal with missing data. For this reason, we performed analyses with and without imputation of missing data.18 A specific difficulty of the TSQM is that there is an established threshold for meaningful changes.7,12 Shikiar and Rentz argue that patients’ expectations influence satisfaction with a drug.8 This issue is important in patients with and without prior treatment with a biologic as experience could greatly influence patients’ expectations.8 Patients’ expectations are not incorporated in the TSQM. Therefore, we compared biologics-experienced with biologics-inexperienced patients in order to deal with the influence of prior experiences. Biologics-experienced and biologics-inexperienced patients showed a significantly different distribution in treatment setting (academic vs. nonacademic). As the TSQM is targeted specifically at the medication itself, and not to factors such as patient– doctor communication, we do not think that different treatment settings influenced TSQM outcomes. This study provides prospective, daily practice data on satisfaction with medication for biologics prescribed in psoriasis, analysed using a validated questionnaire (TSQM). Moreover, separate analyses for biologics-experienced vs. biologics-inexperienced patients are presented. We found that patients treated with adalimumab, etanercept or ustekinumab were significantly more satisfied with their treatment after 3 and 6 months compared with the time before initiation of the studied drug. High satisfaction rates were achieved in this cohort after 3 and 6 months. For the ‘side-effects’ domain, maximum (median) scores were reached. The most ‘room for improvement’ was seen in the ‘effectiveness’ and ‘convenience’ domains (ITT with LOCF analysis). A comparison of biologics-inexperienced versus biologics-experienced showed no differences in satisfaction with medication after 6 months, except in the ‘global satisfaction’ domain, which was significantly better for inexperienced patients. Although biologics are very potent drugs and an important addition for patients with difficult-to-treat psoriasis, further improvement of effectiveness and convenience of use is an important issue in the opinion of patients with psoriasis.
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3 Puig L, Lopez A, Vilarrasa E et al. Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials with different time points. J Eur Acad Dermatol Venereol 2013; DOI: 10.1111/ jdv.12238 (Epub ahead of print). 4 Leidy NK, Vernon M. Perspectives on patient-reported outcomes: content validity and qualitative research in a changing clinical trial environment. Pharmacoeconomics 2008; 26:363–70. 5 Speight J, Barendse SM. FDA guidance on patient reported outcomes. BMJ 2010; 340:c2921. 6 U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaulation and Resarch; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patientreported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes 2006; 4:79. 7 Atkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health 2005; 8(Suppl. 1):S9–24. 8 Shikiar R, Rentz AM. Satisfaction with medication: an overview of conceptual, methodologic, and regulatory issues. Value Health 2004; 7:204–15. 9 Barbosa CD, Balp MM, Kulich K et al. A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence. Patient Prefer Adherence 2012; 6:39–48. 10 Renzi C, Tabolli S, Picardi A et al. Effects of patient satisfaction with care on health-related quality of life: a prospective study. J Eur Acad Dermatol Venereol 2005; 19:712–18. 11 Delestras S, Roustit M, Bedouch P et al. Comparison between two generic questionnaires to assess satisfaction with medication in chronic diseases. PLoS ONE 2013; 8:e56247. 12 Vender R, Lynde C, Gilbert M et al. Etanercept improves quality of life outcomes and treatment satisfaction in patients with moderate to severe plaque psoriasis in clinical practice. J Cutan Med Surg 2012; 16:407–16. 13 Driessen RJ, Bisschops LA, Adang EM et al. The economic impact of high-need psoriasis in daily clinical practice before and after the introduction of biologics. Br J Dermatol 2010; 162:1324–9. 14 Callis Duffin K, Yeung H, Takeshita J et al. Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice. Br J Dermatol 2014; 170:672–80. 15 Nast A, Boehncke WH, Mrowietz U et al. [S3-guidelines for the treatment of psoriasis vulgaris. Update 2011]. J Dtsch Dermatol Ges 2011; 9 (Suppl. 2):S1–104 (in German). 16 Nast A, Boehncke WH, Mrowietz U et al. [S3-guidelines on the treatment of psoriasis vulgaris (English version). Update]. J Dtsch Dermatol Ges 2012; 10 (Suppl. 2):S1–95. 17 Pathirana D, Ormerod AD, Saiag P et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23 (Suppl. 2):1–70. 18 van Lumig PP, Driessen RJ, Kievit W et al. Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice. J Am Acad Dermatol 2013; 68:57–63. 19 Pope J, Thorne JC, Haraoui BP et al. Do patients with active RA have differences in disease activity and perceptions if anti-TNF naive versus anti-TNF experienced? Baseline results of the optimization of adalimumab trial. Med Sci Monit 2012; 18:PI17–20. 20 Armstrong AW, Robertson AD, Wu J et al. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from
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Appendix Conflicts of interest J.M.P.A.v.d.R. carries out clinical trials for AbbVie and Janssen and has received speaking fees from AbbVie, and reimbursement from Janssen, AbbVie and Pfizer for attending a symposium. P.P.M.v.L. has carried out clinical trials for AbbVie and Janssen, has received speaking and consulting fees from Wyeth and Schering-Plough, and has received reimbursement from Janssen, Schering-Plough and Pfizer for attending a symposium. J.Z. carries out trials for AbbVie and Janssen, and has received reimbursement from AbbVie for attending a symposium. P.C.M.v.d.K. serves as a consultant and/or speaker for Galderma, Janssen Cilag, Schering-Plough, Celgene, Centocor, Allmirall, Hermal, UCB, Wyeth, Pfizer, Sofinnova, AbbVie,
© 2014 British Association of Dermatologists
Actelion, Novartis, LEO Pharma, Galapogos, Eli Lilly and Sandoz; and serves as chairman of the data management safety review board for Mitsubishi. All fees were paid directly to the institution or to the International Psoriasis Council. P.C.M.v.d.K. has received research grants from GlaxoSmithKline, Centocor, Wyeth, Pfizer, Celgene, Schering-Plough, Merck Serono, AbbVie, Philips Lighting and Eli Lilly. All grants were paid directly to the institution. M.M.B.S. has received grants from/was involved in clinical trials from AbbVie, Astellas, LEO Pharma and Pfizer; has served as a consultant for AbbVie, Astellas and Pfizer; has given lectures for Pfizer; and has travelled to meetings with Abbott, Pfizer and LEO Pharma. All fees were paid directly to the institution. E.M.G.J.d.J. has received research grants for the independent research fund of the Department of Dermatology, University Medical Centre St Radboud Nijmegen, the Netherlands, from Merck-Serono, Wyeth, Abbott, Pfizer and Janssen, and has acted as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Abbott, Janssen, MSD and Pfizer. M.D.N. serves as a consultant for Janssen. W.P.A. has served as a consultant for AbbVie and Janssen, and travelled to medical congresses with Pfizer, AbbVie and Janssen for 50% of the fees.
British Journal of Dermatology (2014) 170, pp1158–1165
British Journal of Dermatology
T H E R A P E U T I CS
Satisfaction of treatment with biologics is high in psoriasis: results from the Bio-CAPTURE network* €umig,1 M.E. Otero,1 J. Zweegers,1 P.C.M. van de Kerkhof,1 J.M.P.A. van den Reek,1 P.P.M. van Lu 2 2 P.M. Ossenkoppele, M.D. Njoo, J.M. Mommers,3 M.I.A. Koetsier,4 W.P. Arnold,5 B.A.M. Sybrandy-Fleuren,6 A.L.A. Kuijpers,7 M.P.M. Andriessen,8 M.M.B. Seyger,1 W. Kievit9 and E.M.G.J. de Jong1 1
Department Department 3 Department 4 Department 5 Department 6 Department 7 Department 8 Department 2
of of of of of of of of
Dermatology and 9Department of Health Evidence, Radboud University Medical Centre, Nijmegen, the Netherlands Dermatology, Ziekenhuisgroep Twente, Almelo/Hengelo, the Netherlands Dermatology, St. Anna Ziekenhuis, Geldrop, the Netherlands Dermatology, Gelre Ziekenhuizen, Apeldoorn, the Netherlands Dermatology, Ziekenhuis Gelderse Vallei, Ede, the Netherlands Dermatology, Slingeland Ziekenhuis, Doetinchem, the Netherlands Dermatology, Maxima Medisch Centrum, Eindhoven/Veldhoven, the Netherlands Dermatology, Jeroen Bosch Ziekenhuis, Den Bosch, the Netherlands
Summary Correspondence Juul M.P.A. van den Reek. E-mail: [email protected]
Accepted for publication 27 January 2014
Funding sources This study was supported by the University Medical Centre St Radboud Foundation, which received funding for the project from Pfizer, Janssen and AbbVie. Pfizer, Janssen and AbbVie played no role in the design and execution of the study; in data collection, data management, data analysis and interpretation of the data; or manuscript preparation, review and approval.
Conflicts of interest See Appendix. *Plain language summary available online DOI 10.1111/bjd.12862
Background Although the effectiveness of biologics for psoriasis has been measured extensively with objective outcome measures, studies based on subjective, patient-reported outcome measures remain scarce. Objectives To investigate satisfaction with medication, as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) for biologics in daily practice psoriasis care in the first 6 months of treatment; and to identify possible differences in satisfaction with medication between patients experienced (biologics-experienced) and inexperienced (biologics-inexperienced) in the use of biologics. Methods TSQM baseline measurements were compared using measurements taken after 6 months, using the Wilcoxon signed-rank test for paired comparisons. Intention-to-treat with last observation carried forward (ITT with LOCF) and astreated analyses were performed. The difference between biologics-experienced and biologics-inexperienced patients for TSQM was analysed using ITT with LOCF. At 6 months, outcomes for biologics-experienced and biologics-inexperienced patients were compared using the Mann–Whitney U-test. Results One hundred and six patients were eligible for analysis, and treated with etanercept (n = 34), adalimumab (n = 49) or ustekinumab (n = 23). Fifty-four per cent of patients were biologics-inexperienced. A statistically significant improvement was seen in all domains of the TSQM (‘effectiveness’, ‘side-effects’, ‘convenience’ and ‘global satisfaction’) by comparison of months 3 or 6 with baseline (all P ≤ 002). After 6 months, biologics-inexperienced patients scored better on the ‘global satisfaction’ domain than biologics-experienced patients (P < 001). Conclusions We provide a prospective, longitudinal analysis of TSQM for biologics in daily practice psoriasis care. High satisfaction rates were achieved. The ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement.
What’s already known about this topic?
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Maximum satisfaction with medication is thought to be positively related to adherence, health-related quality of life and patients’ preferences.
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Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1159
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As shown in cross-sectional research, patients’ dissatisfaction with treatment plays an important role in psoriasis. Those receiving biologics are the most satisfied with treatment among patients with psoriasis. In an open-label extension trial with etanercept, significant improvement in the ‘global satisfaction’, ‘effectiveness’ and ‘convenience’ domains was achieved after 3 months of treatment.
What does this study add?
• • •
A prospective, longitudinal study on satisfaction with etanercept, adalimumab and ustekinumab for patients with psoriasis in daily practice. Significantly improved satisfaction rates (using the Treatment Satisfaction Questionnaire for Medication) were achieved after 3 and 6 months. As reported by the patients, the ‘effectiveness’ and ‘convenience’ domains showed the most room for improvement. After 6 months, biologics-inexperienced patients scored significantly better on the ‘global satisfaction’ domain than experienced patients.
In recent years, effective targeted biological treatments have become available for the treatment of patients with moderateto-severe psoriasis. The effectiveness of these agents has been measured extensively with objective outcome measures, such as Psoriasis Area and Severity Index scores.1–3 However, in the evaluation of treatments, patient reported outcomes (PROs) are important as well.4–6 An under-reported PRO in the field of psoriasis treatment is ‘satisfaction with medication’. The Treatment Satisfaction Questionnaire for Medication (TSQM) has been developed to gauge satisfaction with medication for different indications.7 This generic questionnaire provides insight into different domains of treatment satisfaction.7 In treating patients with psoriasis, maximum satisfaction with medication should be aimed for as it is thought to be related positively to adherence, health-related quality of life and patients’ preferences.8–11 It also provides insight into what should be improved in the drug itself.8–10 Vender et al. provided an analysis, based on the TSQM, of etanercept in an open-label trial, and found significant improvement in the ‘global satisfaction’, ‘effectiveness’ and ‘convenience’ domains after 3 months of treatment.12 A cross-sectional investigation of treatment satisfaction using the TSQM in a daily practice cohort treated with biologics was carried out by Driessen et al.13 Recently, Callis Duffin et al.14 analysed the TSQM in a cross-sectional study comparing different antipsoriatic treatments. Our study provides a prospective, longitudinal analysis of patients in daily practice starting or switching biologics. The primary objective of this prospective study was to investigate satisfaction with medication, as measured by the TSQM (version II): for biological therapies in daily practice psoriasis care in the first 6 months of treatment. The secondary objective was to identify possible differences in satisfaction with medication between patients experienced and inexperienced in the use of biologics. © 2014 British Association of Dermatologists
Materials and methods The Bio-CAPTURE database Data were extracted from a prospective registry (BioCAPTURE: Continuous Assessment of Psoriasis Treatment Use Registry with Biologics) containing daily practice data from all patients with psoriasis treated with biologics. The registry contains data on effectiveness, PROs and pharmacovigilance. Founded in 2005, it is based in the Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands. Eight regional nonacademic centres have participated in this registry since 2011, and all consecutive patients treated with biologics are enrolled in it. Patients were treated, according to the opinion of the treating dermatologist, with etanercept, adalimumab, infliximab or ustekinumab. Preferably, patients were treated according to the regimens recommended by the European Medicines Agency label, and European and Dutch national guidelines for treatment with biologics.15–17 If necessary, dosage adjustments, interval changes and/or combination therapy with topical or other antipsoriatic systemic therapies were applied. The registry was approved by our medical ethics committee. According to Dutch law, informed consent was not mandatory for this noninterventional study; however, it is obtained from every newly included patient. Treatment satisfaction questionnaire for medication From January 2010 to July 2013, all patients starting a biologic for the first time or switching to another biologic were asked to fill out a TSQM (version II). This questionnaire is included in the Bio-CAPTURE study. In this time frame, etanercept, adalimumab and ustekinumab were equally available in daily practice. Patients received questionnaires at British Journal of Dermatology (2014) 170, pp1158–1165
1160 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
baseline and after 3 and 6 months, or until the moment of discontinuation (when patients stopped before 6 months of therapy). The TSQM (version II) is a generic, multilinguistically validated questionnaire developed for different patients and medications, and is therefore applicable to our patient group. The TSQM covers four important domains of satisfaction with medication: efficacy, convenience, general satisfaction and side-effects. The scores for the domains range from 0 (extremely dissatisfied) to 100 (extremely satisfied).7 The questionnaire refers to the time frame 2–3 weeks prior to completion of the questionnaire. Therefore, the baseline measures provide information about the last treatment used before the initiation of the biologic. Data collection and extraction At every visit, all data on effectiveness and safety (adverse events) were collected on a standardized case report form (CRF) by a trained physician or nurse. The data manager entered the data into the Bio-CAPTURE database, and checked the source documents for incomplete or incorrect data on the CRF. Every 3 months, patients received TSQM questionnaires by mail. After retrieving completed TSQM questionnaires, scores were entered into the Bio-CAPTURE database. Data were extracted from the database and imported into SPSS Statistics 20 (IBM, Armonk, NY, U.S.A) for further analysis. Statistical analysis TSQM data on etanercept, adalimumab and ustekinumab were analysed. Descriptive statistics [means SD or medians (range)] were used to summarize TSQM data. The four TSQM subdomains were analysed separately. To explore the additional effects of biologics on each domain, baseline measurements were compared with measurements taken after 3 and 6 months using a Wilcoxon signed rank test. In order to detect possible bias due to missing values or selection, two analyses were performed: (i) an intention-totreat (ITT) with last observation carried forward (ITT with LOCF) analysis, which represented the most conservative approach; and (ii) an as-treated analysis, which represented the most positive approach.18 In the ITT with LOCF analysis, missing values for month 3, were imputed by baseline values; missing values for month 6 were imputed with month 3 values. To investigate the influence of prior experiences with biological treatments on TSQM, patients were classified as ‘biologics-experienced’ (prior treatment with biologics) or ‘biologics-inexperienced’ (no prior treatment with biologics). Descriptive statistics were summarized, and differences in the main characteristics for biologics-experienced and biologicsinexperienced patients were tested. Categorical variables were compared using Pearson’s v2-test or Fisher’s exact test. Continuous variables with a parametric distribution were analysed using an independent t-test; continuous variables with a nonparametric distribution were analysed using a Mann–Whitney U-test (ITT with LOCF). At month 6, the outcomes of biBritish Journal of Dermatology (2014) 170, pp1158–1165
ologics-experienced and biologics-inexperienced patients were compared directly using the Mann–Whitney U-test to identify possible differences in satisfaction at this end point. Additionally, other factors that could theoretically influence satisfaction with medication were analysed using a Mann–Whitney U-test for month 6 outcomes (ITT with LOCF). These variables were age, disease duration and sex. Patients aged < 40 years and ≥ 40 years were compared. We chose this cut-off point in order to take into account important age-specific issues, such as studying, first working years and family planning (< 40 years) vs. late working years with established careers and a higher prevalence of comorbidities (≥ 40 years). With regard to disease duration, we compared patients with a relatively short disease duration (< 10 years) with patients with more established psoriasis (≥ 10 years). A P-value < 005 was considered significant in all analyses. SPSS Statistics 20 (IBM) was used to perform the analyses.
Results Patient and treatment characteristics One hundred and seventeen unique patients were included in this study. Eleven patients were excluded: nine patients had less than 6 months follow up < 6 months and two were lost to follow-up. Therefore, 106 patients using adalimumab (n = 49, 46%), etanercept (n = 34, 32%) or ustekinumab (n = 23, 22%) were eligible for analysis. Patient characteristics are presented in Table 1. Little more than half of the patients were biologics-inexperienced (n = 57, 54%). Baseline median scores for TSQM were 50% (range 0–1000) for ‘effectiveness’, 92% (range 83–1000) for ‘side-effects’, 67% (range 0–1000) for ‘convenience’ and 58% (range 0–1000) for ‘global satisfaction’. Baseline measures represent satisfaction with medication in the period directly preceding the start of the studied biologic. The most frequently used agents in this period were methotrexate monotherapy (n = 27, 27%) and etanercept monotherTable 1 Patient characteristics (n = 106) General characteristics Sex (male) Age (years), mean SD Duration of disease (years), median (range)a Experience with prior biologics Experienced (non-naive) Inexperienced (naive) Status at time of analysis Active user of biologic for > 4 months Discontinued biologic < 4 months Hospital type Academic Nonacademic
62 (585) 482 123 204 (24–536) 49 (462) 57 (538) 99 (934) 7 (66) 71 (670) 35 (330)
Data are n (%) unless otherwise indicated. aData missing from three patients at the time of entry into the study.
© 2014 British Association of Dermatologists
Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1161 Table 2 Systemic antipsoriatic treatment in the 4 weeks prior to initiation of the study biologic (n = 101)a Treatment
n (%)
No systemic antipsoriatic Methotrexate Etanercept Ciclosporin Adalimumab Furamic acid esters UVB Acitretin Adalimumab + methotrexate Dithranol Infliximab Ustekinumab
30 (297) 27 (267) 15 (149) 9 (89) 8 (79) 4 (40) 2 (20) 2 (20) 1 (10) 1 (10) 1 (10) 1 (10)
UVB, ultraviolet B; aFive cases unknown.
apy (n = 15, 15%). Thirty patients (30%) were not receiving systemic antipsoriatic therapy in this time frame. Other therapies used in this period are outlined in Table 2. Satisfaction with treatment after 3 and 6 months Using ITT with LOCF, median scores at month 3 were 67% for the ‘effectiveness’, 100% for the ‘side-effects’, 67% for the ‘convenience’ and 75% for the ‘global satisfaction’ domains. At month 6, the median scores were 67% for ‘effectiveness’, 100% for ‘side-effects’, 78% for ‘convenience’ and 83% for ‘global satisfaction’. As can be seen from these scores, the ‘effectiveness’ and ‘convenience’ domains show the most room for improvement at month 6. On all domains, a statistically significant improvement was seen by comparing subsequent measurements (months 3 and 6) with baseline (all P ≤ 002, paired Wilcoxon signed-rank test) (Fig. 1). Comparable results were seen in the as-treated analysis: all domains showed statistically significant improvement when comparing subsequent measurements (months 3 and 6) with the baseline (all P ≤ 002, paired Wilcoxon signed-rank test) (Fig. 2).
Satisfaction with treatment for biologics-experienced and biologics-inexperienced patients Table 3 shows the patient and treatment characteristics of biologics-experienced and biologics-inexperienced patients. Age, sex and body mass index were distributed equally among groups. Biologics-experienced patients used adalimumab more frequently, whereas biologics-inexperienced patients used etanercept more frequently. More biologics-inexperienced patients were treated in a nonacademic centre. Disease duration was longer among biologics-experienced patients. The TSQM responses of both biologics-experienced and biologicsinexperienced patients were analysed (ITT with LOCF): both groups showed statistically significant improvements in the ‘efficacy’, ‘convenience’ and ‘global satisfaction’ domains (all P < 005, paired Wilcoxon signed-rank test) after 3 and after 6 months compared with baseline. Biologics-inexperienced patients achieved a statistically significant improvement (P < 001) in the ‘side-effects’ domain after 3 and after 6 months compared with baseline. In contrast, no statistically significant difference was achieved in this domain by biologics-experienced patients (P = 080 and P = 030 after 3 and 6 months, respectively). To compare directly month 6 outcomes for biologics-experienced vs. biologics-inexperienced patients, a Mann–Whitney Utest was carried out (ITT with LOCF). This analysis revealed no statistically significant differences between the groups in the ‘effectiveness’ (P = 014), ‘side-effects’ (P = 028) and ‘convenience’ (P = 063) domains. However, in the ‘global satisfaction’ domain, significantly better outcomes were measured for biologics-inexperienced patients (P < 001) (Fig. 3). Satisfaction with treatment with regard to age, disease duration and sex The 6-month TSQM responses of patients aged < 40 years (n = 25) and ≥ 40 years (n = 81) were compared. Using a Mann–Whitney U-test, no statistically significant differences in the end point measures were found between groups in the ‘effectiveness’ (P = 089), ‘side-effects’ (P = 060), ‘convenience’ (P = 005) or ‘global satisfaction’ (P = 100) domains.
Fig 1. Treatment Satisfaction Questionnaire for Medication (TSQM) measures for patients with psoriasis treated with biologics (intention-to-treat with last observation carried forward analysis). Whiskers represent 10–90th percentiles. *Statistically significant improvement on Wilcoxon signed-rank test compared with baseline measurements. © 2014 British Association of Dermatologists
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1162 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
Fig 2. Treatment Satisfaction Questionnaire for Medication (TSQM) measures for psoriasis patients treated with biologics (as-treated analysis). Whiskers represent 10–90th percentiles. *Statistically significant improvement on Wilcoxon signed-rank test compared with baseline measurements. Table 3 Patient and treatment characteristics of biologics-experienced and biologics-inexperienced patients (n = 106) Not experienced (n = 57) Sex (male) Age (years), mean SD Duration of disease (years), mean SD Body mass index, median (range)/ mean SD Diabetes Treatment Adalimumab Etanercept Ustekinumab Hospital type Academic Nonacademic
Experienced (n = 49)
P-valuea b
33 (58) 479 126
29 (59) 486 121
089 078c
191 117d
252 128e
001c
272 (186–532)f
292 54g
020h
3 (5)i
7 (14)
019j
24 (42) 24 (42) 9 (16)
25 (51) 10 (20) 14 (29)
– – 004b
32 (56) 25 (44)
39 (80) 10 (20)
– 001b
Data are n (%) unless otherwise indicated. aBased on the difference between naive and non-naive patients. bPearson’s v2-test. c Independent t-test. dMissing the data of one patient. eMissing the data of two patients. fMissing the data of 12 patients. gMissing the data of 13 patients. hMann–Whitney U-test. iMissing the data of two patients. jFisher’s exact test.
The 6-month TSQM responses of patients with a relatively short disease duration (< 10 years, n = 17) vs. patients with more established psoriasis (≥ 10 years, n = 86) were compared. This comparison revealed a statistically significant difference in the ‘convenience’ domain in favour of patients with a longer disease duration (≥ 10 years) (P = 0.04), no statistically significant difference between groups for the ‘effectiveness’ (P = 087), ‘side effects’ (P = 050), and ‘global satisfaction’ (P = 054) domains was seen at month 6 (MannWhitney U test). No statistically significant difference between men (n = 62) and women (n = 44) was seen at month 6 for all TSQM domains: ‘effectiveness’ (P = 012), ‘side-effects’ (P = 047), British Journal of Dermatology (2014) 170, pp1158–1165
‘convenience’ (P = 054) and ‘global satisfaction’ (P = 046) (Mann-Whitney U test).
Discussion For the total group of patients treated with adalimumb, etanercept or ustekinumab, a statistical significant improvement was seen on all domains of TSQM comparing baseline with month 3 and 6 measures. Both biologics-experienced and biologics-inexperienced patients showed significant improvements in most domains of the TSQM. Biologicsinexperienced patients scored significantly better in the ‘global satisfaction’ domain compared with biologics-experienced patients after 6 months of treatment. Driessen et al.13 cross-sectionally investigated treatment satisfaction in a biologics-treated daily practice cohort, and found the highest scores in the ‘side-effects’ (91%) domain, followed by the ‘convenience’ (80%), ‘global satisfaction’ (78%) and ‘effectiveness’ (71%) domains. In an open-label study, Vender et al.12 measured, using the TSQM, treatment satisfaction with etanercept in psoriasis over 1 year. Over time, a significant improvement was seen in all domains, with the exception of the ‘side-effects’ domain. Our study provides an analysis of satisfaction with medication for three different biologics (adalimumab, etanercept and ustekinumab) instead of an analysis on etanercept alone. In addition, our study has a prospective and longitudinal study design. It is conceivable that satisfaction rates in patients who have received prior biologics could be influenced by former experiences, for example with effectiveness, side-effects or practical issues with other drugs. However, in patients with rheumatoid arthritis (RA), the baseline level of treatment satisfaction with different medications was not different between patients experienced and naive for antitumour necrosis factora agents.19 Our findings correspond with the results obtained in this RA study: we found no differences between baseline scores for TSQM for biologics-experienced and biologicsinexperienced patients (data not shown). Moreover, we found that both groups improved significantly in all domains of the TSQM in the first 6 months. The only exception was that biologics-experienced patients achieved no significant © 2014 British Association of Dermatologists
Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al. 1163
Effecveness
Side-effects
Convenience
Global sasfacon
Fig 3. TSQM measures for biologics-experienced and biologics-inexperienced patients. Each figure shows medians with interquartile ranges (whiskers). Asterisks represent a significant improvement (P < 005) compared with baseline for the specific Treatment Satisfaction Questionnaire for Medication (TSQM) domain. Colour of asterisks corresponds with colour of lines.
improvement in the ‘side-effects’ domain. This finding was due to a ceiling effect: this subgroup of patients started with a (maximum) median score of 100% at baseline, which did not change after 3 or 6 months. When comparing the absolute scores directly between biologics-experienced and biologics-inexperienced patients after 6 months, significantly higher scores were seen in biologics-inexperienced patients in the ‘global satisfaction’ domain (P < 001). A possible explanation for this could be that, over time, experienced patients have become more used to the positive effects of biologics. Patients with a longer disease duration (≥ 10 years) scored significantly better in the ‘convenience’ domain than patients with a shorter disease duration (< 10 years). This could be explained by their long treatment history and experiences, which make them more easily accustomed to new treatments. © 2014 British Association of Dermatologists
In general, patients’ dissatisfaction with treatment plays an important role in the field of psoriasis. Although patients treated with biologics show the highest satisfaction, there is still room for improvement, as shown in cross-sectional research.13,14,20–22 The National Psoriasis Foundation found that 43% of patients with severe psoriasis (self-reported body surface area > 10%) were dissatisfied with their treatment.20 A survey by van Cranenburgh et al.22 revealed that patients with psoriasis rated ‘treatment effectiveness’ as the most important issue related to treatment satisfaction. It is therefore important to realize that we found this to be the factor with the most ‘room for improvement’. Our results correspond with the outcomes of Vender et al.12 and Driessen et al.,13 who also found the most room for improvement to be in the ‘effectiveness’ domain. This indicates that we should focus on ways to improve satisfaction with effectiveness when prescribing treatBritish Journal of Dermatology (2014) 170, pp1158–1165
1164 Satisfaction with biologics treatment in psoriasis, J.M.P.A. van den Reek et al.
ment with biologics in daily practice. These results suggest that the development of treatments with higher efficacy is still needed in order to provide a solution for this unmet medical need. In addition, satisfaction with the effectiveness of a drug could also rely on other factors, such as expectations of effectiveness. A limitation of our study was that head-to-head comparisons between agents were not opportune owing to group size. Furthermore, responder bias is an issue in questionnaire research, and we had to deal with missing data. For this reason, we performed analyses with and without imputation of missing data.18 A specific difficulty of the TSQM is that there is an established threshold for meaningful changes.7,12 Shikiar and Rentz argue that patients’ expectations influence satisfaction with a drug.8 This issue is important in patients with and without prior treatment with a biologic as experience could greatly influence patients’ expectations.8 Patients’ expectations are not incorporated in the TSQM. Therefore, we compared biologics-experienced with biologics-inexperienced patients in order to deal with the influence of prior experiences. Biologics-experienced and biologics-inexperienced patients showed a significantly different distribution in treatment setting (academic vs. nonacademic). As the TSQM is targeted specifically at the medication itself, and not to factors such as patient– doctor communication, we do not think that different treatment settings influenced TSQM outcomes. This study provides prospective, daily practice data on satisfaction with medication for biologics prescribed in psoriasis, analysed using a validated questionnaire (TSQM). Moreover, separate analyses for biologics-experienced vs. biologics-inexperienced patients are presented. We found that patients treated with adalimumab, etanercept or ustekinumab were significantly more satisfied with their treatment after 3 and 6 months compared with the time before initiation of the studied drug. High satisfaction rates were achieved in this cohort after 3 and 6 months. For the ‘side-effects’ domain, maximum (median) scores were reached. The most ‘room for improvement’ was seen in the ‘effectiveness’ and ‘convenience’ domains (ITT with LOCF analysis). A comparison of biologics-inexperienced versus biologics-experienced showed no differences in satisfaction with medication after 6 months, except in the ‘global satisfaction’ domain, which was significantly better for inexperienced patients. Although biologics are very potent drugs and an important addition for patients with difficult-to-treat psoriasis, further improvement of effectiveness and convenience of use is an important issue in the opinion of patients with psoriasis.
References 1 Kim IH, West CE, Kwatra SG et al. Comparative efficacy of biologics in psoriasis: a review. Am J Clin Dermatol 2012; 13:365–74. 2 Lin VW, Ringold S, Devine EB. Comparison of ustekinumab with other biological agents for the treatment of moderate to severe plaque psoriasis: a Bayesian network meta-analysis. Arch Dermatol 2012; 148:1403–10.
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3 Puig L, Lopez A, Vilarrasa E et al. Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials with different time points. J Eur Acad Dermatol Venereol 2013; DOI: 10.1111/ jdv.12238 (Epub ahead of print). 4 Leidy NK, Vernon M. Perspectives on patient-reported outcomes: content validity and qualitative research in a changing clinical trial environment. Pharmacoeconomics 2008; 26:363–70. 5 Speight J, Barendse SM. FDA guidance on patient reported outcomes. BMJ 2010; 340:c2921. 6 U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research; U.S. Department of Health and Human Services FDA Center for Biologics Evaulation and Resarch; U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patientreported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes 2006; 4:79. 7 Atkinson MJ, Kumar R, Cappelleri JC, Hass SL. Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health 2005; 8(Suppl. 1):S9–24. 8 Shikiar R, Rentz AM. Satisfaction with medication: an overview of conceptual, methodologic, and regulatory issues. Value Health 2004; 7:204–15. 9 Barbosa CD, Balp MM, Kulich K et al. A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence. Patient Prefer Adherence 2012; 6:39–48. 10 Renzi C, Tabolli S, Picardi A et al. Effects of patient satisfaction with care on health-related quality of life: a prospective study. J Eur Acad Dermatol Venereol 2005; 19:712–18. 11 Delestras S, Roustit M, Bedouch P et al. Comparison between two generic questionnaires to assess satisfaction with medication in chronic diseases. PLoS ONE 2013; 8:e56247. 12 Vender R, Lynde C, Gilbert M et al. Etanercept improves quality of life outcomes and treatment satisfaction in patients with moderate to severe plaque psoriasis in clinical practice. J Cutan Med Surg 2012; 16:407–16. 13 Driessen RJ, Bisschops LA, Adang EM et al. The economic impact of high-need psoriasis in daily clinical practice before and after the introduction of biologics. Br J Dermatol 2010; 162:1324–9. 14 Callis Duffin K, Yeung H, Takeshita J et al. Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice. Br J Dermatol 2014; 170:672–80. 15 Nast A, Boehncke WH, Mrowietz U et al. [S3-guidelines for the treatment of psoriasis vulgaris. Update 2011]. J Dtsch Dermatol Ges 2011; 9 (Suppl. 2):S1–104 (in German). 16 Nast A, Boehncke WH, Mrowietz U et al. [S3-guidelines on the treatment of psoriasis vulgaris (English version). Update]. J Dtsch Dermatol Ges 2012; 10 (Suppl. 2):S1–95. 17 Pathirana D, Ormerod AD, Saiag P et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009; 23 (Suppl. 2):1–70. 18 van Lumig PP, Driessen RJ, Kievit W et al. Results of three analytical approaches on long-term efficacy of etanercept for psoriasis in daily practice. J Am Acad Dermatol 2013; 68:57–63. 19 Pope J, Thorne JC, Haraoui BP et al. Do patients with active RA have differences in disease activity and perceptions if anti-TNF naive versus anti-TNF experienced? Baseline results of the optimization of adalimumab trial. Med Sci Monit 2012; 18:PI17–20. 20 Armstrong AW, Robertson AD, Wu J et al. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from
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Appendix Conflicts of interest J.M.P.A.v.d.R. carries out clinical trials for AbbVie and Janssen and has received speaking fees from AbbVie, and reimbursement from Janssen, AbbVie and Pfizer for attending a symposium. P.P.M.v.L. has carried out clinical trials for AbbVie and Janssen, has received speaking and consulting fees from Wyeth and Schering-Plough, and has received reimbursement from Janssen, Schering-Plough and Pfizer for attending a symposium. J.Z. carries out trials for AbbVie and Janssen, and has received reimbursement from AbbVie for attending a symposium. P.C.M.v.d.K. serves as a consultant and/or speaker for Galderma, Janssen Cilag, Schering-Plough, Celgene, Centocor, Allmirall, Hermal, UCB, Wyeth, Pfizer, Sofinnova, AbbVie,
© 2014 British Association of Dermatologists
Actelion, Novartis, LEO Pharma, Galapogos, Eli Lilly and Sandoz; and serves as chairman of the data management safety review board for Mitsubishi. All fees were paid directly to the institution or to the International Psoriasis Council. P.C.M.v.d.K. has received research grants from GlaxoSmithKline, Centocor, Wyeth, Pfizer, Celgene, Schering-Plough, Merck Serono, AbbVie, Philips Lighting and Eli Lilly. All grants were paid directly to the institution. M.M.B.S. has received grants from/was involved in clinical trials from AbbVie, Astellas, LEO Pharma and Pfizer; has served as a consultant for AbbVie, Astellas and Pfizer; has given lectures for Pfizer; and has travelled to meetings with Abbott, Pfizer and LEO Pharma. All fees were paid directly to the institution. E.M.G.J.d.J. has received research grants for the independent research fund of the Department of Dermatology, University Medical Centre St Radboud Nijmegen, the Netherlands, from Merck-Serono, Wyeth, Abbott, Pfizer and Janssen, and has acted as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Abbott, Janssen, MSD and Pfizer. M.D.N. serves as a consultant for Janssen. W.P.A. has served as a consultant for AbbVie and Janssen, and travelled to medical congresses with Pfizer, AbbVie and Janssen for 50% of the fees.
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