Scandinavian Journal of Rheumatology
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project I Ahlstrand, I Thyberg, T Falkmer, Ö Dahlström & M Björk To cite this article: I Ahlstrand, I Thyberg, T Falkmer, Ö Dahlström & M Björk (2015) Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project, Scandinavian Journal of Rheumatology, 44:4, 259-264, DOI: 10.3109/03009742.2014.997285 To link to this article: http://dx.doi.org/10.3109/03009742.2014.997285
Published online: 19 Mar 2015.
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Date: 15 November 2015, At: 14:14
Scand J Rheumatol 2015;44:259–264
259
Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project I Ahlstrand1, I Thyberg2, T Falkmer1,3,4, Ö Dahlström5, M Björk1,6
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1 School of Health Sciences, Jönköping University, Jönköping, 2Division of Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden, 3School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia, 4Department of Medical and Health Sciences, Linköping University, Linköping, 5The Swedish Institute for Disability Research, Department of Behavioral Sciences and Learning, Linköping University, and 6Rehabilitation Center and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996–1998 and 463 patients were included in the second cohort (TIRA-2) during 2006–2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.
Treatment strategies in rheumatoid arthritis (RA) have changed dramatically over the past 20 years with the introduction of early diagnosis and early instituted disease-modifying anti-rheumatic drugs (DMARDs) including biological agents. This strategy has proved highly advantageous (1–3) and as a result disease activity has decreased. However, women achieve remission less often than men (4, 5). Despite new treatment strategies, disability has shown a less favourable course compared to disease activity (6, 7). Pain and activity limitations are dominant concerns in RA, affecting women more than men (4, 5, 8). To our knowledge it remains unknown whether patients with contemporary treated early RA report less pain and fewer activity limitations compared with their counterparts 10 years ago. Consequently, pain and activity limitations during the 3 years after diagnosis in women and men with contemporary treated early RA
Inger Ahlstrand, School of Health Sciences, Jököping University, Box 1026, SE-551 11 Jönköping Sweden. E-mail: [email protected] Accepted 8 December 2014
were compared with their counterparts who were diagnosed 10 years earlier.
Method The TIRA project A total of 320 patients fulfilling at least four of the seven 1987 revised American College of Rheumatology (ACR-87) classification criteria (9) or at least morning stiffness lasting more than 60 min, symmetric arthritis and arthritis of the small joints were included at time of diagnosis in the Swedish Early Intervention in RA cohort (TIRA-1) between 1996 and 1998. Clinical routines were established during regular visits. Data regarding disease activity, pain, and activity limitations were recorded. Besides medication, patients were continuously offered multi-professional rehabilitative interventions based on individual needs. Ten years later, during 2006–2009, after the introduction of biological agents, 463 patients were enrolled in a second cohort (TIRA-2) according to corresponding criteria and routines as in TIRA-1.
© 2015 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation DOI: 10.3109/03009742.2014.997285
www.scandjrheumatol.dk
www.scandjrheumatol.dk 5.3 (1.1) 49 51 0 3.6 (1.3) 19 81 0 3.5 (1.4) 33 67 0 3.6 (1.4) 26 68 6
5.2 (1.3)
50 50 0
3.9 (1.4)
20 80 0
3.7 (1.4)
24 76 1
3.6 (1.4)
31 63 5
Men n ¼ 85
ns ns
ns ns
ns ns
ns ns
Gender differences p-value
8 75 17
2.7 (1.3)
5 82 13
2.9 (1.3)
5 88 7
3.0 (1.3)
6 94 0
5.1 (1.3)
Women n ¼ 251
11 83 6–
2.3 (1.1)
9 85 6
2.3 (1.1)
6 90 4
2.4 (1.1)
8 91 1
5.0 (1.3)
Men n ¼ 122
TIRA-2
< 0.001 0.009
< 0.001 ns
< 0.001 ns
ns ns
Gender differences p-value
30þ 65 5–
3.6 (1.4)
27þ 73 < 1–
3.6 (1.4)
20þ 80 0–
3.8 (1.4)
50þ 50– 0
5.2 (1.2)
TIRA-1
TIRA-2
9– 77 13þ
2.6 (1.3)
6þ 83 11–
2.7 (1.3)
5– 89 6þ
2.8 (1.3)
7– 93þ < 0.5
5.1 (1.3)
TIRA, Early Intervention in RA study; DAS28, 28-joint count Disease Activity Score; DMARD, disease-modifying anti-rheumatic drug; ns, not significant. þ indicates cells with standard residuals > 2. – indicates cells with standard residuals < –2.
Inclusion DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 1 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 2 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 3 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use
Women n ¼ 191
TIRA-1
Table 1. Disease activity and prescribed medication in women and men across TIRA-1 and TIRA-2.
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< 0.001 < 0.001
< 0.001 < 0.001
< 0.001 < 0.001
ns < 0.001
TIRA-1/TIRA-2 differences p-value
Total
260 I Ahlstrand et al
Pain and activity limitations in early RA
261
60,00 VAS Pain
50,00 40,00 30,00 20,00 10,00 0,00 Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
80,00 60,00 SF-36
The 276 patients in TIRA-1 (69% women) and 373 patients in TIRA-2 (67% women) remaining at the 3-year follow-up were included in this study. The mean age at inclusion in TIRA-2 was slightly higher (59 years, SD ¼ 15) than in TIRA-1 (56 years, SD ¼ 15) (p ¼ 0.013). The drop-outs (TIRA-1; 44 patients, TIRA-2; 90 patients) were significantly older (TIRA-1: 9 years older, p < 0.001; TIRA-2: 5 years older, p ¼ 0.004) than the study groups but no differences were seen in the 28-joint count Disease Activity Score (DAS28) (10), Health Assessment Questionnaire (HAQ) score (11), or pain on a Visual Analogue Scale (VAS). DAS28 and prescribed medication (traditional DMARDs and/or biologics) were registered at inclusion and after 1 year (Y1), 2 years (Y2), and 3 years (Y3).
TIRA-2
TIRA-1
40,00 20,00
Pain and activity limitations
0,00
Pain intensity was reported on the VAS and by the subscale bodily pain (BP) in the 36-item Short Form Health Survey (SF-36) (12). Activity limitations were assessed by the Swedish version of the HAQ (7, 11).
1,20 1,00
Statistical analyses In addition to descriptive statistics, independent samples t-tests, χ 2-tests, Pearson’s correlation test, and analysis of variance (ANOVA) with the Sidak post-hoc test were applied. Values of p < 0.05 were considered statistically significant.
Ethics The study protocol was approved by the local ethics committee in Linköping, Sweden.
Results
HAQ
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Patients
0,80 0,60 0,40 0,20 0,00 Women Men
Figure 1. Time course for pain intensity (VAS Pain, 0–100), bodily pain (SF-36 BP, 0–100), and activity limitations (HAQ, 0–3) in TIRA-1 and TIRA-2, across women and men. Mean values and 95% confidence intervals are displayed. TIRA, Early Intervention in RA; VAS, Visual Analogue Scale; HAQ, Health Assessment Questionnaire; SF-36, 36item Short Form Health Survey; BP, bodily pain.
Patient characteristics The men were significantly older than the women in both cohorts (TIRA-1 p ¼ 0.025, TIRA-2 p ¼ 0.001) but there were no significant gender differences regarding disease activity or medication at inclusion. Disease activity was high in both genders and in both cohorts at inclusion. Disease activity did not differ significant between cohorts at inclusion but DAS28 was thereafter significantly lower in TIRA-2 (Table 1). In TIRA-2, women showed significantly higher disease activity at all follow-ups compared to men. Significantly more DMARDs were prescribed in TIRA-2 than in TIRA-1 and significantly more women than men were prescribed DMARDs in TIRA-2 at Y3 (Table 1).
Pain and activity limitations in the cohorts over time At inclusion, across genders and in both cohorts, pain and activity limitations were pronounced. Overall improvement during the first 3 years after inclusion was statistically significant for pain and activity limitations in all groups regardless of cohort or gender (all p < 0.001) (Figure 1). Pain intensity in both cohorts was significantly reduced from inclusion to Y1 and thereafter stable (p < 0.001), with the exception of pain intensity in women in TIRA-1, which did not differ between inclusion and Y1. In both cohorts, bodily pain and activity limitations
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www.scandjrheumatol.dk
49.8 (27.8) 34.4 (20.5) 0.8 (0.5)
34.8 (27) 55.2 (23.8) 0.4 (0.4)
33.6 (25.4) 54.6 (23.9) 0.5 (0.5)
34.5 (24.0) 52.4 (19.2) 0.4 (0.4)
47.4 (23.5) 35.4 (18.5) 0.9 (0.6)
40.8 (26.7) 50.5 (22.4) 0.7 (0.6)
36.6 (26.1) 52.8 (23.2) 0.7 (0.6)
36.0 (25.1) 54.0 (24.0) 0.8 (0.6)
Men n ¼ 85
ns ns < 0.001
ns ns 0.003
ns ns < 0.001
ns ns ns
p-value*
29.3 (24.4) 60.0 (24.5) 0.5 (0.5)
30.3 (23.8) 60.9 (23.6) 0.6 (0.5)
30.8 (23.8) 57.6 (22.7) 0.5 (0.5)
54.4 (23.4) 33.0 (18.6) 1.0 (0.6)
Women n ¼ 251
20.4 (20.3) 69.4 (23.1) 0.4 (0.5)
23.0 (21.3) 70.0 (21.3) 0.3 (0.4)
22.9 (21.3) 65.5 (25.9) 0.4 (0.5)
48.7 (24.6) 34.6 (21.8) 0.9 (0.6)
Men n ¼ 122
0.006 0.019 < 0.001
< 0.001 0.004 0.001
< 0.001 < 0.001 ns
0.003 < 0.001 0.008
0.001 0.012 ns
< 0.001 0.004 < 0.001 0.011 0.001 0.003
ns ns ns
Men Differences between cohorts p-value*
35.6 (24.8) 53.5 (22.7) 0.7 (0.6)
35.7 (25.9) 53.3 (23.4) 0.7 (0.6)
38.9 (26.9) 51.9 (22.9) 0.6 (0.6)
48.1 (24.9) 35.1 (19.1) 0.9 (0.6 )
Total TIRA-1
Comparisons of cohorts
0.002 ns 0.020
Women Differences between cohorts p-value*
0.007 0.004 < 0.001
0.004 0.03 0.015
0.04 ns 0.008
p-value*
TIRA-2 (n ¼ 373)
26.4 (23.5) 62.9 (24.4) 0.5 (0.5)
27.9 (23.2) 63.8 (23.2) 0.5 (0.5)
28.2 (23.2) 60.1 (23.9) 0.5 (0.5)
52.6 (23.9) 33.5 (19.8) 1.0 (0.6 )
Total TIRA-2
< 0.001 < 0.001 < 0.001
< 0.001 < 0.001 < 0.001
< 0.001 < 0.001 < 0.001
0.03 ns 0.023
Total differences TIRA-1/TIRA-2 p-value*
TIRA, Early Intervention in RA; SD, standard deviation; VAS, Visual Analogue Scale; HAQ, Health Assessment Questionnaire; SF-36, 36-item Short Form Health Survey; BP, bodily pain; ns, not significant. *Difference between groups (independent samples t-test).
Inclusion Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 1 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 2 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 3 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3)
Women n ¼ 191
TIRA-1 (n ¼ 276)
Table 2. Mean (SD) for pain and activity limitation at inclusion and at follow-ups after 1 year, 2 years, and 3 years in TIRA-1 and TIRA-2.
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262 I Ahlstrand et al
Pain and activity limitations in early RA
across genders were significantly reduced from inclusion to Y1 (p < 0.001) but thereafter stable.
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Differences in pain and activity limitations between cohorts The TIRA-2 cohort reported significantly higher pain intensity at inclusion but significantly lower pain intensity than TIRA-1 patients at follow-ups Y1, Y2, and Y3. Bodily pain did not differ at inclusion between cohorts but was thereafter significant lower in TIRA-2 at follow-ups (Table 2). TIRA-2 patients reported significantly higher activity limitations than TIRA-1 patients at inclusion but lower activity limitations at all follow-ups than TIRA-1 patients. When comparing the subgroups women and men between cohorts, men in TIRA-2 reported no significant differences compared to men in TIRA-1 in pain at inclusion and in activity limitations at Y1 and Y3.
Differences in pain and activity limitations between women and men within cohorts In TIRA-1, no differences were seen at any time points except for women reporting significantly more activity limitations than men at Y1, Y2, and Y3 (Table 2). In TIRA-2, men reported significantly lower pain intensity than women at all time points. There were no significant differences between women and men in bodily pain at inclusion but men reported lower bodily pain at Y1, Y2, and Y3. Women reported more activity limitations than men at all time points (Table 2).
Discussion At inclusion, across both genders and in both cohorts, disease activity, pain, and activity limitations were pronounced but improvements were seen across genders and cohorts during the first year. Disease activity decreased to a greater extent, coinciding with increased prescription of DMARDs in the contemporary treated TIRA-2 cohort. Both women and men in TIRA-2 reported lower pain and less activity limitations at the follow-ups compared to TIRA-1 a decade earlier. However, pain and activity limitations were still pronounced in TIRA-2 compared to reference values (8), with women being affected more than men. Disease activity, pain, and activity limitations at inclusion in TIRA-1 are similar to other early RA studies from the period before the introduction of biological agents (6). This study’s two cohorts showed no significant differences at inclusion regarding DAS28 and bodily pain. However, the TIRA-2 patients were prescribed more conventional DMARDs, and reported higher pain intensity and activity limitations at inclusion than their counterparts in TIRA-1. The largest improvement in pain and activity limitations that
263
occurred between inclusion and the first follow-up in both cohorts is consistent with other studies (13–16). Despite this reduction, the mean HAQ scores were still high compared to Swedish referents and pain levels are also still pronounced in TIRA-2 (8). Activity limitations reduced significantly during the first year in accordance with other studies (4, 5), especially in women in TIRA-2 compared to those in TIRA-1. A corresponding pattern was seen for pain intensity and bodily pain. At the time of inclusion within both TIRA cohorts, women had more activity limitations than men, consistent with other cohort studies (4–6, 17, 18). This gender disparity might be explained by higher pain sensitivity and less muscular strength in women but also because men tend to overestimate their functional capacity (5). Pain intensity showed a similar pattern for change over time and differences between genders, in accordance with bodily pain. The SF-36 subscale bodily pain was used as it reflects the interference between pain and daily activities as a complement to pain VAS (19). Patients in TIRA-2 were older and had higher average HAQ scores than the patients in TIRA-1. One possible explanation for these higher scores may be related to the age difference, as the mean HAQ score increases with age by 0.01 units per year in patients with RA (20). Another difference was that pain was rated higher at inclusion in TIRA-2 than in TIRA-1. Regardless of this difference, the results revealed lower HAQ scores and pain intensity over time in TIRA-2 than in TIRA-1. Despite more prescribed DMARDs and lower DAS28 in TIRA-2 compared to TIRA-1, pain and activity limitations were still remarkable in our well-treated TIRA-2 cohort. In addition to medication, early multi-professional interventions were given by occupational therapists and physiotherapists based on patients’ individual needs. Our results indicate a need for further investigation of treatment strategies, including medications and individualized rehabilitation interventions directed towards the ability to participate in activities of daily living. To provide effective rehabilitation, the patients’ perspectives of pain, activity limitations, and participation restrictions need to be further examined. Acknowledgements We thank the patients and TIRA co-workers, especially Ylva Billing and Magnus Husberg. This study was supported by the Medical Research Council of Southeast Sweden (FORSS) and the Academy for Health and Care Jönköping County Council (Futurum).
References 1. Mottonen T, Hannonen P, Korpela M, Nissilä M, Kautiainen H, Ilonen J, et al. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 2002;46:894–8. 2. Emery P. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol Suppl 2002;66:3–8.
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264 3. Verstappen SM. Outcomes of early rheumatoid arthritis – the WHO ICF framework. Best Pract Res Rheumatol 2013; 27:555–70. 4. Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study. Arthritis Res Ther 2009;11:R7. 5. Ahlmén M, Svensson B, Albertsson K, Forslind K, Hafstrom I. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage. Ann Rheum Dis 2010;69:230–3. 6. Hallert E, Bjork M, Dahlstoom O, Skogh T, Thyberg I. Disease activity and disability in women and men with early rheumatoid arthritis (RA): an 8-year followup of a Swedish early RA project. Arthritis Care Res 2012;64:1101–7. 7. Thyberg I, Dahlstrom O, Bjork M, Arvidsson P, Thyberg M. Potential of the HAQ score as clinical indicator suggesting comprehensive multidisciplinary assessments: the Swedish TIRA cohort 8 years after diagnosis of RA. Clin Rheumatol 2012;31:775–83. 8. Bjork M, Thyberg I, Skogh T, Gerdle B. Hand function and activity limitation according to health assessment questionnaire in patients with rheumatoid arthritis and healthy referents: 5-year followup of predictors of activity limitation (The Swedish TIRA Project). J Rheumatol 2007;34:296–302. 9. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24. 10. Prevoo ML, van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8. 11. Ekdahl C, Eberhardt K, Andersson SI, Svensson B. Assessing disability in patients with rheumatoid arthritis. Scand J Rheumatol 1988;17:263–71.
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I Ahlstrand et al 12. Sullivan M, Karlsson J, Ware JE Jr. The Swedish SF-36 Health Survey – I. Evaluation of data quality, scaling assumptions, reliability and construct validity across general populations in Sweden. Soc Sci Med 1995;41:1349–58. 13. Austad C, Kvien TK, Olsen IC, Uhlig T. Health status has improved more in women than in men with rheumatoid arthritis from 1994 to 2009: results from the Oslo rheumatoid arthritis register. Ann Rheum Dis 2015;74:148–55. 14. Uhlig T, Heiberg T, Mowinckel P, Kvien TK. Rheumatoid arthritis is milder in the new millennium: health status in patients with rheumatoid arthritis 1994-2004. Ann Rheum Dis 2008;67:1710–15. 15. Norton S, Sacker A, Dixey J, Done J, Williams P, Young A. Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality. Rheumatology (Oxford) 2013;52:2016–24. 16. Krishnan E, Lingala B, Bruce B, Fries JF. Disability in rheumatoid arthritis in the era of biological treatments. Ann Rheum Dis 2012;71:213–18. 17. McWilliams DF, Zhang W, Mansell JS, Kiely PDW, Young A, Walsh DA. Predictors of change in bodily pain in early rheumatoid arthritis: an inception cohort study. Arthritis Care Res 2012; 64:1505–13. 18. Tengstrand B, Ahlmén M, Hafstrom I. The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years. J Rheumatol 2004;31:214–22. 19. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res 2011;63(Suppl 11):S240–52. 20. Sokka T, Kautiainen H, Hannonen P, Pincus T. Changes in Health Assessment Questionnaire disability scores over five years in patients with rheumatoid arthritis compared with the general population. Arthritis Rheum 2006;54:3113–18.
ISSN: 0300-9742 (Print) 1502-7732 (Online) Journal homepage: http://www.tandfonline.com/loi/irhe20
Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project I Ahlstrand, I Thyberg, T Falkmer, Ö Dahlström & M Björk To cite this article: I Ahlstrand, I Thyberg, T Falkmer, Ö Dahlström & M Björk (2015) Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project, Scandinavian Journal of Rheumatology, 44:4, 259-264, DOI: 10.3109/03009742.2014.997285 To link to this article: http://dx.doi.org/10.3109/03009742.2014.997285
Published online: 19 Mar 2015.
Submit your article to this journal
Article views: 93
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=irhe20 Download by: [Washington University in St Louis]
Date: 15 November 2015, At: 14:14
Scand J Rheumatol 2015;44:259–264
259
Pain and activity limitations in women and men with contemporary treated early RA compared to 10 years ago: the Swedish TIRA project I Ahlstrand1, I Thyberg2, T Falkmer1,3,4, Ö Dahlström5, M Björk1,6
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1 School of Health Sciences, Jönköping University, Jönköping, 2Division of Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden, 3School of Occupational Therapy and Social Work, CHIRI, Curtin University, Perth, WA, Australia, 4Department of Medical and Health Sciences, Linköping University, Linköping, 5The Swedish Institute for Disability Research, Department of Behavioral Sciences and Learning, Linköping University, and 6Rehabilitation Center and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
Objectives: To study differences regarding pain and activity limitations during the 3 years following diagnosis in women and men with contemporary treated early RA compared with their counterparts who were diagnosed 10 years earlier. Method: This study was based on patients recruited to the Early Intervention in RA (TIRA) project. In the first cohort (TIRA-1) 320 patients were included in time for diagnosis during 1996–1998 and 463 patients were included in the second cohort (TIRA-2) during 2006–2009. Disease activity, pain intensity (Visual Analogue Scale, VAS), bodily pain (BP) in the 36-item Short Form Health Survey (SF-36), activity limitations (Health Assessment Questionnaire, HAQ), and medication were reported at inclusion and at follow-up after 1, 2, and 3 years. Results: Disease activity, pain, and activity limitations were pronounced at inclusion across both genders and in both cohorts, with some improvement observed during the first year after diagnosis. Disease activity did not differ between cohorts at inclusion but was significantly lower at the follow-ups in the TIRA-2 cohort, in which the patients were prescribed traditional disease-modifying anti-rheumatic drugs (DMARDs) and biological agents more frequently. In TIRA-2, patients reported significantly lower pain and activity limitations at all follow-ups, with men reporting lower pain than women. Women reported significantly higher activity limitations at all time points in TIRA-2. Conclusions: Pain and activity limitations were still pronounced in the contemporary treated early RA cohort compared with their counterparts diagnosed 10 years earlier and both of these factors need to be addressed in clinical settings.
Treatment strategies in rheumatoid arthritis (RA) have changed dramatically over the past 20 years with the introduction of early diagnosis and early instituted disease-modifying anti-rheumatic drugs (DMARDs) including biological agents. This strategy has proved highly advantageous (1–3) and as a result disease activity has decreased. However, women achieve remission less often than men (4, 5). Despite new treatment strategies, disability has shown a less favourable course compared to disease activity (6, 7). Pain and activity limitations are dominant concerns in RA, affecting women more than men (4, 5, 8). To our knowledge it remains unknown whether patients with contemporary treated early RA report less pain and fewer activity limitations compared with their counterparts 10 years ago. Consequently, pain and activity limitations during the 3 years after diagnosis in women and men with contemporary treated early RA
Inger Ahlstrand, School of Health Sciences, Jököping University, Box 1026, SE-551 11 Jönköping Sweden. E-mail: [email protected] Accepted 8 December 2014
were compared with their counterparts who were diagnosed 10 years earlier.
Method The TIRA project A total of 320 patients fulfilling at least four of the seven 1987 revised American College of Rheumatology (ACR-87) classification criteria (9) or at least morning stiffness lasting more than 60 min, symmetric arthritis and arthritis of the small joints were included at time of diagnosis in the Swedish Early Intervention in RA cohort (TIRA-1) between 1996 and 1998. Clinical routines were established during regular visits. Data regarding disease activity, pain, and activity limitations were recorded. Besides medication, patients were continuously offered multi-professional rehabilitative interventions based on individual needs. Ten years later, during 2006–2009, after the introduction of biological agents, 463 patients were enrolled in a second cohort (TIRA-2) according to corresponding criteria and routines as in TIRA-1.
© 2015 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation DOI: 10.3109/03009742.2014.997285
www.scandjrheumatol.dk
www.scandjrheumatol.dk 5.3 (1.1) 49 51 0 3.6 (1.3) 19 81 0 3.5 (1.4) 33 67 0 3.6 (1.4) 26 68 6
5.2 (1.3)
50 50 0
3.9 (1.4)
20 80 0
3.7 (1.4)
24 76 1
3.6 (1.4)
31 63 5
Men n ¼ 85
ns ns
ns ns
ns ns
ns ns
Gender differences p-value
8 75 17
2.7 (1.3)
5 82 13
2.9 (1.3)
5 88 7
3.0 (1.3)
6 94 0
5.1 (1.3)
Women n ¼ 251
11 83 6–
2.3 (1.1)
9 85 6
2.3 (1.1)
6 90 4
2.4 (1.1)
8 91 1
5.0 (1.3)
Men n ¼ 122
TIRA-2
< 0.001 0.009
< 0.001 ns
< 0.001 ns
ns ns
Gender differences p-value
30þ 65 5–
3.6 (1.4)
27þ 73 < 1–
3.6 (1.4)
20þ 80 0–
3.8 (1.4)
50þ 50– 0
5.2 (1.2)
TIRA-1
TIRA-2
9– 77 13þ
2.6 (1.3)
6þ 83 11–
2.7 (1.3)
5– 89 6þ
2.8 (1.3)
7– 93þ < 0.5
5.1 (1.3)
TIRA, Early Intervention in RA study; DAS28, 28-joint count Disease Activity Score; DMARD, disease-modifying anti-rheumatic drug; ns, not significant. þ indicates cells with standard residuals > 2. – indicates cells with standard residuals < –2.
Inclusion DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 1 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 2 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use Year 3 DAS28 (0–10) Medication No medication, % DMARDs, % use Biologics, % use
Women n ¼ 191
TIRA-1
Table 1. Disease activity and prescribed medication in women and men across TIRA-1 and TIRA-2.
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< 0.001 < 0.001
< 0.001 < 0.001
< 0.001 < 0.001
ns < 0.001
TIRA-1/TIRA-2 differences p-value
Total
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60,00 VAS Pain
50,00 40,00 30,00 20,00 10,00 0,00 Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
Incl. Y1
Y2
Y3
80,00 60,00 SF-36
The 276 patients in TIRA-1 (69% women) and 373 patients in TIRA-2 (67% women) remaining at the 3-year follow-up were included in this study. The mean age at inclusion in TIRA-2 was slightly higher (59 years, SD ¼ 15) than in TIRA-1 (56 years, SD ¼ 15) (p ¼ 0.013). The drop-outs (TIRA-1; 44 patients, TIRA-2; 90 patients) were significantly older (TIRA-1: 9 years older, p < 0.001; TIRA-2: 5 years older, p ¼ 0.004) than the study groups but no differences were seen in the 28-joint count Disease Activity Score (DAS28) (10), Health Assessment Questionnaire (HAQ) score (11), or pain on a Visual Analogue Scale (VAS). DAS28 and prescribed medication (traditional DMARDs and/or biologics) were registered at inclusion and after 1 year (Y1), 2 years (Y2), and 3 years (Y3).
TIRA-2
TIRA-1
40,00 20,00
Pain and activity limitations
0,00
Pain intensity was reported on the VAS and by the subscale bodily pain (BP) in the 36-item Short Form Health Survey (SF-36) (12). Activity limitations were assessed by the Swedish version of the HAQ (7, 11).
1,20 1,00
Statistical analyses In addition to descriptive statistics, independent samples t-tests, χ 2-tests, Pearson’s correlation test, and analysis of variance (ANOVA) with the Sidak post-hoc test were applied. Values of p < 0.05 were considered statistically significant.
Ethics The study protocol was approved by the local ethics committee in Linköping, Sweden.
Results
HAQ
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Patients
0,80 0,60 0,40 0,20 0,00 Women Men
Figure 1. Time course for pain intensity (VAS Pain, 0–100), bodily pain (SF-36 BP, 0–100), and activity limitations (HAQ, 0–3) in TIRA-1 and TIRA-2, across women and men. Mean values and 95% confidence intervals are displayed. TIRA, Early Intervention in RA; VAS, Visual Analogue Scale; HAQ, Health Assessment Questionnaire; SF-36, 36item Short Form Health Survey; BP, bodily pain.
Patient characteristics The men were significantly older than the women in both cohorts (TIRA-1 p ¼ 0.025, TIRA-2 p ¼ 0.001) but there were no significant gender differences regarding disease activity or medication at inclusion. Disease activity was high in both genders and in both cohorts at inclusion. Disease activity did not differ significant between cohorts at inclusion but DAS28 was thereafter significantly lower in TIRA-2 (Table 1). In TIRA-2, women showed significantly higher disease activity at all follow-ups compared to men. Significantly more DMARDs were prescribed in TIRA-2 than in TIRA-1 and significantly more women than men were prescribed DMARDs in TIRA-2 at Y3 (Table 1).
Pain and activity limitations in the cohorts over time At inclusion, across genders and in both cohorts, pain and activity limitations were pronounced. Overall improvement during the first 3 years after inclusion was statistically significant for pain and activity limitations in all groups regardless of cohort or gender (all p < 0.001) (Figure 1). Pain intensity in both cohorts was significantly reduced from inclusion to Y1 and thereafter stable (p < 0.001), with the exception of pain intensity in women in TIRA-1, which did not differ between inclusion and Y1. In both cohorts, bodily pain and activity limitations
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49.8 (27.8) 34.4 (20.5) 0.8 (0.5)
34.8 (27) 55.2 (23.8) 0.4 (0.4)
33.6 (25.4) 54.6 (23.9) 0.5 (0.5)
34.5 (24.0) 52.4 (19.2) 0.4 (0.4)
47.4 (23.5) 35.4 (18.5) 0.9 (0.6)
40.8 (26.7) 50.5 (22.4) 0.7 (0.6)
36.6 (26.1) 52.8 (23.2) 0.7 (0.6)
36.0 (25.1) 54.0 (24.0) 0.8 (0.6)
Men n ¼ 85
ns ns < 0.001
ns ns 0.003
ns ns < 0.001
ns ns ns
p-value*
29.3 (24.4) 60.0 (24.5) 0.5 (0.5)
30.3 (23.8) 60.9 (23.6) 0.6 (0.5)
30.8 (23.8) 57.6 (22.7) 0.5 (0.5)
54.4 (23.4) 33.0 (18.6) 1.0 (0.6)
Women n ¼ 251
20.4 (20.3) 69.4 (23.1) 0.4 (0.5)
23.0 (21.3) 70.0 (21.3) 0.3 (0.4)
22.9 (21.3) 65.5 (25.9) 0.4 (0.5)
48.7 (24.6) 34.6 (21.8) 0.9 (0.6)
Men n ¼ 122
0.006 0.019 < 0.001
< 0.001 0.004 0.001
< 0.001 < 0.001 ns
0.003 < 0.001 0.008
0.001 0.012 ns
< 0.001 0.004 < 0.001 0.011 0.001 0.003
ns ns ns
Men Differences between cohorts p-value*
35.6 (24.8) 53.5 (22.7) 0.7 (0.6)
35.7 (25.9) 53.3 (23.4) 0.7 (0.6)
38.9 (26.9) 51.9 (22.9) 0.6 (0.6)
48.1 (24.9) 35.1 (19.1) 0.9 (0.6 )
Total TIRA-1
Comparisons of cohorts
0.002 ns 0.020
Women Differences between cohorts p-value*
0.007 0.004 < 0.001
0.004 0.03 0.015
0.04 ns 0.008
p-value*
TIRA-2 (n ¼ 373)
26.4 (23.5) 62.9 (24.4) 0.5 (0.5)
27.9 (23.2) 63.8 (23.2) 0.5 (0.5)
28.2 (23.2) 60.1 (23.9) 0.5 (0.5)
52.6 (23.9) 33.5 (19.8) 1.0 (0.6 )
Total TIRA-2
< 0.001 < 0.001 < 0.001
< 0.001 < 0.001 < 0.001
< 0.001 < 0.001 < 0.001
0.03 ns 0.023
Total differences TIRA-1/TIRA-2 p-value*
TIRA, Early Intervention in RA; SD, standard deviation; VAS, Visual Analogue Scale; HAQ, Health Assessment Questionnaire; SF-36, 36-item Short Form Health Survey; BP, bodily pain; ns, not significant. *Difference between groups (independent samples t-test).
Inclusion Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 1 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 2 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3) Year 3 Pain VAS (0–100) SF-36 BP (0–100) HAQ (0–3)
Women n ¼ 191
TIRA-1 (n ¼ 276)
Table 2. Mean (SD) for pain and activity limitation at inclusion and at follow-ups after 1 year, 2 years, and 3 years in TIRA-1 and TIRA-2.
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across genders were significantly reduced from inclusion to Y1 (p < 0.001) but thereafter stable.
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Differences in pain and activity limitations between cohorts The TIRA-2 cohort reported significantly higher pain intensity at inclusion but significantly lower pain intensity than TIRA-1 patients at follow-ups Y1, Y2, and Y3. Bodily pain did not differ at inclusion between cohorts but was thereafter significant lower in TIRA-2 at follow-ups (Table 2). TIRA-2 patients reported significantly higher activity limitations than TIRA-1 patients at inclusion but lower activity limitations at all follow-ups than TIRA-1 patients. When comparing the subgroups women and men between cohorts, men in TIRA-2 reported no significant differences compared to men in TIRA-1 in pain at inclusion and in activity limitations at Y1 and Y3.
Differences in pain and activity limitations between women and men within cohorts In TIRA-1, no differences were seen at any time points except for women reporting significantly more activity limitations than men at Y1, Y2, and Y3 (Table 2). In TIRA-2, men reported significantly lower pain intensity than women at all time points. There were no significant differences between women and men in bodily pain at inclusion but men reported lower bodily pain at Y1, Y2, and Y3. Women reported more activity limitations than men at all time points (Table 2).
Discussion At inclusion, across both genders and in both cohorts, disease activity, pain, and activity limitations were pronounced but improvements were seen across genders and cohorts during the first year. Disease activity decreased to a greater extent, coinciding with increased prescription of DMARDs in the contemporary treated TIRA-2 cohort. Both women and men in TIRA-2 reported lower pain and less activity limitations at the follow-ups compared to TIRA-1 a decade earlier. However, pain and activity limitations were still pronounced in TIRA-2 compared to reference values (8), with women being affected more than men. Disease activity, pain, and activity limitations at inclusion in TIRA-1 are similar to other early RA studies from the period before the introduction of biological agents (6). This study’s two cohorts showed no significant differences at inclusion regarding DAS28 and bodily pain. However, the TIRA-2 patients were prescribed more conventional DMARDs, and reported higher pain intensity and activity limitations at inclusion than their counterparts in TIRA-1. The largest improvement in pain and activity limitations that
263
occurred between inclusion and the first follow-up in both cohorts is consistent with other studies (13–16). Despite this reduction, the mean HAQ scores were still high compared to Swedish referents and pain levels are also still pronounced in TIRA-2 (8). Activity limitations reduced significantly during the first year in accordance with other studies (4, 5), especially in women in TIRA-2 compared to those in TIRA-1. A corresponding pattern was seen for pain intensity and bodily pain. At the time of inclusion within both TIRA cohorts, women had more activity limitations than men, consistent with other cohort studies (4–6, 17, 18). This gender disparity might be explained by higher pain sensitivity and less muscular strength in women but also because men tend to overestimate their functional capacity (5). Pain intensity showed a similar pattern for change over time and differences between genders, in accordance with bodily pain. The SF-36 subscale bodily pain was used as it reflects the interference between pain and daily activities as a complement to pain VAS (19). Patients in TIRA-2 were older and had higher average HAQ scores than the patients in TIRA-1. One possible explanation for these higher scores may be related to the age difference, as the mean HAQ score increases with age by 0.01 units per year in patients with RA (20). Another difference was that pain was rated higher at inclusion in TIRA-2 than in TIRA-1. Regardless of this difference, the results revealed lower HAQ scores and pain intensity over time in TIRA-2 than in TIRA-1. Despite more prescribed DMARDs and lower DAS28 in TIRA-2 compared to TIRA-1, pain and activity limitations were still remarkable in our well-treated TIRA-2 cohort. In addition to medication, early multi-professional interventions were given by occupational therapists and physiotherapists based on patients’ individual needs. Our results indicate a need for further investigation of treatment strategies, including medications and individualized rehabilitation interventions directed towards the ability to participate in activities of daily living. To provide effective rehabilitation, the patients’ perspectives of pain, activity limitations, and participation restrictions need to be further examined. Acknowledgements We thank the patients and TIRA co-workers, especially Ylva Billing and Magnus Husberg. This study was supported by the Medical Research Council of Southeast Sweden (FORSS) and the Academy for Health and Care Jönköping County Council (Futurum).
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