Highlights
- •Pain progression is heterogeneous in people with rheumatoid arthritis.
- •Persistent pain is predicted by high disability.
- •Even when inflammation resolves, the commonest trajectory is persistent pain.
- •Additional pain management might help people with rheumatoid arthritis.
Abstract
Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern
treatments suppress inflammation, yet pain remains a major problem for many people
with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable
pain trajectories when receiving treatment, and that baseline characteristics will
predict trajectory allocation. Growth mixture modelling was used to identify discrete
trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early
RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics
(n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline
predictor variables between trajectories. The role of inflammation was examined in
a subgroup analysis of people with normal levels of inflammatory markers after 3 years.
The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout
3 years of follow-up of >1 standard deviation worse than the UK general population
average. Discrete persistent pain (59–79% of cohort participants) and resolving pain
(19–27%) trajectories were identified in each cohort. In Early RA Network, a third
trajectory displaying persistently low pain (23%) was also identified. In people with
normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent
pain trajectory. When trajectories were compared, greater disability (adjusted odds
ratio = 2.3–2.5 per unit baseline Health Assessment Questionnaire score) and smoking
history (adjusted odds ratio = 1.6–1.8) were risk factors for persistent pain trajectories
in each cohort. In conclusion, distinct trajectories indicate patient subgroups with
very different pain prognosis during treatment for RA. Inflammation does not fully
explain the pain trajectories, and noninflammatory factors as well as acute phase
response predict which trajectory an individual will follow. Targeted treatments additional
to those which suppress inflammation might reduce the long-term burden of arthritis
pain.
Perspective
Immunosuppression decreases inflammation in RA, but pain outcomes are less favorable.
Discrete persistent and resolving pain trajectories were identified after treatment,
both in early and established RA. Smoking and greater disability at baseline predicted
persistent pain. Identifying patient subgroups with a poor pain prognosis could enable
adjunctive treatment to improve outcomes.
Key words
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References
- Remaining pain in early rheumatoid arthritis patients treated with methotrexate.Arthritis Care Res. 2016; 68: 1061-1068
- The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum. 1988; 31: 315-324
- Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: Meta-analysis of randomized controlled trials.Arthritis Care Res. 2010; 62: 984-992
- Heterogeneous disease trajectories explain variable radiographic, function and quality of life outcomes in the Canadian Early Arthritis Cohort (CATCH).PLoS One. 2015; 10: e0135327
- The Stanford Health Assessment Questionnaire: A review of its history, issues, progress, and documentation.J Rheumatol. 2003; 30: 167-178
- Reductions in radiographic progression in early rheumatoid arthritis over twenty-five years: Changing contribution from rheumatoid factor in two multicenter UK inception cohorts.Arthritis Care Res. 2017; 69: 1809-1817
- Smoking and rheumatoid arthritis.Int J Mol Sci. 2014; 15: 22279-22295
- Ultrasound Doppler but not temporal summation of pain predicts DAS28 response in rheumatoid arthritis: A prospective cohort study.Rheumatology (Oxford). 2016; 55: 1091-1098
- Rheumatoid arthritis patients after initiation of a new biologic agent: Trajectories of disease activity in a large multinational cohort study.EBioMedicine. 2016; 11: 302-306
- Trajectories of physical activity over two years in persons with rheumatoid arthritis.Arthritis Care Res (Hoboken). 2016; 68: 1069-1077
- The longitudinal course of fatigue in rheumatoid arthritis: Results from the Norfolk Arthritis Register.J Rheumatol. 2015; 42: 2059-2065
- Physical activity levels and functional performance in the osteoarthritis initiative: A graded relationship.Arthritis Rheum. 2011; 63: 127-136
- Personality is of central concern to understand health: Towards a theoretical model for health psychology.Health Psychol Rev. 2013; 7: S32-S70
- Future directions in personality, occupational and medical selection: Myths, misunderstandings, measurement, and suggestions.Adv Health Sci Educ Theory Pract. 2017; 22: 387-399
- The Early Rheumatoid Arthritis Network (ERAN).Musculoskel Care. 2004; 2: 240-244
- Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial.Arthritis Rheum. 2008; 58: S126-S135
- Comparison of the response to infliximab or etanercept monotherapy with the response to cotherapy with methotrexate or another disease-modifying antirheumatic drug in patients with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register.Arthritis Rheum. 2006; 54: 1786-1794
Hyrich KL, Watson KD, Lunt M, Symmons DP: Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008. Rheumatology (Oxford) 50:117-123, 2011
- General and disease-specific pain trajectories as predictors of social and political outcomes in arthritis and cancer.BMC Med. 2018; 16: 51
- Assessment of the SF-36 version 2 in the United Kingdom.J Epidemiol Community Health. 1999; 53: 46-50
- A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis.Arthritis Res Ther. 2015; 17: 11
- Contribution of the subjective components of the disease activity score to the response to biologic treatment in rheumatoid arthritis.Arthritis Care Res (Hoboken). 2015; 67: 923-928
- Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity–the Early RA Network (ERAN).Rheumatology (Oxford, England). 2011; 50: 926-931
- Rheumatoid factor and anti-CCP autoantibodies in rheumatoid arthritis: A review.Clin Lab Sci. 2008; 21: 15-18
- Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: A longitudinal observational study.Arthritis Res Ther. 2011; 13: R83
- Pattern-mixture models for multivariate incomplete data with covariates.Biometrics. 1996; 52: 98-111
- Discordant inflammation and pain in early and established rheumatoid arthritis: Latent class analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.Arthritis Res Ther. 2016; 18: 295
- Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis.BMC Rheumatol. 2018; 2: 8
- Factors predicting pain and early discontinuation of tumour necrosis factor-alpha-inhibitors in people with rheumatoid arthritis: Results from the British society for rheumatology biologics register.BMC Musculoskelet Disord. 2016; 17: 337
- Predictors of change in bodily pain in early rheumatoid arthritis: An inception cohort study.Arthritis Care Res (Hoboken). 2012; 64: 1505-1513
- Growth modeling with nonignorable dropout: Alternative analyses of the STAR*D antidepressant trial.Psychol Methods. 2011; 16: 17-33
- Association of joint inflammation with pain sensitization in knee osteoarthritis: The Multicenter Osteoarthritis Study.Arthritis Rheumatol. 2016; 68: 654-661
- Rheumatoid arthritis—the management of rheumatoid arthritis in adults.HMSO, London2009
- Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts.Semin Arthritis Rheum. 2014; 44: 131-144
- Trajectories of functional limitation in early rheumatoid arthritis and their association with mortality.Rheumatology (Oxford, England). 2013; 52: 2016-2024
- Distinct psychological distress trajectories in rheumatoid arthritis: Findings from an inception cohort.J Psychosom Res. 2011; 71: 290-295
- Pain and psychological health status over a 10-year period in patients with recent onset rheumatoid arthritis.Ann Rheum Dis. 2007; 66: 1195-1201
- Pain thresholds in rheumatoid arthritis: The effect of tender point counts and disease duration.J Rheumatol. 2012; 39: 28-31
- Fibromyalgic rheumatoid arthritis and disease assessment.Rheumatology (Oxford). 2010; 49: 924-928
- The evidence base for psychological interventions for rheumatoid arthritis: A systematic review of reviews.Int J Nurs Stud. 2018; 82: 20-29
- Smoking and pain: Pathophysiology and clinical implications.Anesthesiology. 2010; 113: 977-992
- Trajectories of pain severity in juvenile idiopathic arthritis: Results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.Pain. 2018; 159: 57-66
- Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat-to-target strategy.Arthritis Care Res (Hoboken). 2014; 66: 625-630
- British Society for Rheumatology Biologics Register.Ann Rheum Dis. 2003; 62: ii28-29
- Look beyond the disease activity score of 28 joints (DAS28): Tender points influence the DAS28 in patients with rheumatoid arthritis.J Rheumatol. 2012; 39: 22-27
Van Riel PL: Disease activity score in rheumatoid arthritis. 2018. Available at: http://www.das-score.nl/das28/en/; Accessed September 10, 2018
- Physical activity in patients with rheumatoid arthritis.Joint Bone Spine. 2016; 83: 265-270
- SF-36 health survey: Manual and interpretation guide.2nd ed. QualityMetric Inc, Lincoln, RI2000
- The development of fibromyalgia–I: Examination of rates and predictors in patients with rheumatoid arthritis (RA).Pain. 2011; 152: 291-299
Article info
Publication history
Published online: January 15, 2019
Accepted:
January 2,
2019
Received in revised form:
December 6,
2018
Received:
September 6,
2018
Footnotes
E.F. and D.A.W. contributed equally to this study.
Funded by an iCRP grant from Pfizer UK (ref: WI190792).
D.A.W. and D.F.M. declare grant support from Pfizer. This study was funded by an iCRP grant from Pfizer UK (ref: WI190792). D.A.W. declares consultancy work for Pfizer and GlaxoSmithKline. The other authors have no disclosures.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
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© 2019 by the American Pain Society
