Pain patterns in early rheumatoid arthritis

Abstract: Study I: Widespread non-joint pain in early rheumatoid arthritis. Objective: The aim of the study was to assess the development of widespread non-joint pain (WNP) in a cohort of patients with early rheumatoid arthritis (RA), the associated health-related quality of life (HRQoL), and clinical and demographical risk factors for WNP. Methods: Incident cases with RA, from the Swedish population-based study Epidemiological Investigation of Rheumatoid Arthritis (EIRA), with a follow-up of at least 3 years, constituted the study population. WNP was defined as pain outside the joints in all four body quadrants and was assessed at the 3-year follow-up. Patients who reported WNP were compared to patients without WNP regarding HRQoL, measured by the Short Form-36, at 3 years, and clinical and demographical characteristics at the time of RA diagnosis. Results: A total of 749 patients constituted the study sample, of whom 25 were excluded after reporting having severe pain already before RA diagnosis. At the 3-year follow-up, 8% of the patients reported having WNP as well as statistically significant worse HRQoL. At the time of RA diagnosis, the patients with WNP had worse pain and pain-related features, while no difference was seen in the inflammatory parameters. Conclusion: WNP occurs in a substantial subset of patients with RA, also early in the course of the disease, and the HRQoL for these patients is significantly reduced. Patients who develop WNP at 3 years are distinguishable already at the time of diagnosis by displaying more pronounced pain ratings together with an average level of inflammatory disease activity. Study II: Unmet needs in rheumatoid arthritis: A subgroup of patients with high levels of pain, fatigue, and psychosocial distress 3 years after diagnosis. Objective: The study objective was to identify subgroups of patients with rheumatoid arthritis (RA) based on their health status 3 years after diagnosis and to assess potential associations to clinical presentation at diagnosis. Methods: This observational study included patients with RA with 3-year follow-up data from the Swedish Epidemiological Investigation of RA (EIRA) study, collected from 2011 to 2018. Hierarchical agglomerative cluster analysis, based on symptoms of pain, fatigue, sleep quality, mood disturbances, and overall health-related quality of life (HRQoL), was used to identify subgroups 3 years after diagnosis. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for the associations between the subgroups and patient characteristics at diagnosis. Results: A total of 1055 individuals constituted the study population, of whom 1011 had complete data on the clustering variables and were thereby eligible for analysis (73% women, median age 58 years). The following three clusters were identified: Cluster 1 (466 patients with good health status), Cluster 2 (398 patients in an intermediate group) and Cluster 3 (147 patients with high levels of pain and fatigue together with markedly impaired HRQoL). Cluster 3 was associated to higher baseline pain (RR: 3.71 [95% CI: 2.14-6.41]), global health (RR: 6.60 [95% CI: 3.53-12.33]) and Stanford Health Assessment Questionnaire (RR: 4.40 [95% CI: 2.46-7.87]), compared with cluster 1 (highest compared to lowest quartiles). An inverse association was seen for baseline swollen joint count (RR: 0.51 [95% CI: 0.34-0.85]). Conclusion: A subgroup of patients with RA experience high levels of pain, fatigue, and psychosocial distress 3 years after diagnosis. This subgroup displayed pronounced pain and functional disabilities already at diagnosis. Study III: Failure to reach treatment targets despite being in inflammatory remission among patients with early rheumatoid arthritis: Associations to the use of disease-modifying antirheumatic drugs. Objective: The study objective was to assess the proportion of patients with early rheumatoid arthritis (RA) who fail to reach formal treatment targets despite being in inflammatory remission, and to assess patterns of use of disease-modifying antirheumatic drugs (DMARD’s), in comparison with patients who are likewise in inflammatory remission but who reach the formal treatment targets. Methods: Patients newly diagnosed with RA were identified in the Swedish Rheumatology Quality Register (SRQ) (n = 11,784). Disease activity score based on 28 joints (DAS28) and DMARD-treatment were assessed at RA diagnosis and at 3-, 6-, 12-, and 24 months thereafter. Inflammatory remission was defined as: swollen joint count (0-28) = 0 and C-reactive protein <10 mg/L and normal erythrocyte sedimentation rate. Primary treatment targets were DAS28 remission (<2.6) and DAS28 low disease activity (LDA) (≤3.2). The proportion of patients in inflammatory remission who failed to reach the DAS28 targets was assessed at each follow-up visit. Patients who failed to reach DAS28 targets despite being in inflammatory remission were compared with patients in inflammatory remission who reached treatment targets, in terms of new DMARD starts during follow-up. Risk ratios (RR) and 95% confidence intervals (CI) for DMARD starts were estimated with Poisson regression. Results: Overall, 34%, 39%, 44%, and 47%, respectively, were in inflammatory remission at 3, 6, 12, and 24 months. Among these, 20%, 22%, 20%, and 19%, respectively, failed to reach DAS28 remission, and 8%, 9%, 7%, and 8%, respectively, failed to reach DAS28 LDA. Patients who failed to reach DAS28 targets despite being in inflammatory remission at the same visit were more likely to start a new DMARD treatment (RR (95% CI) at 6 months = 1.59 (1.29-1.96), 12 months = 1.52 (1.23-1.87)), and 24 months = 1.47 (1.20-1.80) when DAS28 remission was the target, and at 3 months = 1.35 (1.06-1.71), 6 months = 1.84 (1.42-2.39), 12 months = 1.71 (1.29-2.27), and 24 months = 1.78 (1.39-2.27) when DAS28 LDA was the target. The start of a new DMARD did not affect the likelihood of reaching the treatment target at the subsequent visit for these patients. Conclusion: A substantial proportion of patients with early RA who are in inflammatory remission fail to reach formal treatment targets. These patients might be at risk of overtreatment with DMARD’s.