Objective. To evaluate the impact of polymyalgia rheumatica (PMR) on clinical outcomes and quality of life (QOL); the relationship between laboratory measures and clinical outcomes, and changes in QOL; and agreement between rheumatologists in confirming the initial diagnosis. Methods. We conducted a prospective study of 129 participants in 8 hospitals in England who met a modified version of the Jones and Hazleman criteria and had not started steroid therapy. The main outcome measures were response to steroids after 3 weeks (minimum 50% improvement in proximal pain, morning stiffness <30 minutes, acute-phase response not elevated), relapses, QOL as measured by the Short Form 36 and Health Assessment Questionnaire, and diagnosis reassessment at 1 year. Results. At 3 weeks, 55% of participants failed to meet our definition of a complete response to steroid therapy. Both physical and mental QOL at presentation were substantially lower than general population norms and improved by 12.6 (95% confidence interval [95% CI] 10.8, 14.4) and 11.2 (95% CI 8.5, 13.8) points, respectively, at 1 year. Proximal pain and longer morning stiffness were significantly associated with lower physical QOL during followup, whereas erythrocyte sedimentation rate was most strongly associated with lower mental QOL during followup. There was moderate agreement between clinicians in confirming the PMR diagnosis (kappa coefficients 0.49 -0.65). Conclusion. PMR is a heterogeneous disease with a major impact on QOL. Ongoing monitoring should include disease activity based on symptoms, emergence of alternative diagnoses, and early referral of atypical and severe cases.
Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5–20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n = 164), patients with low/absent synovial B cell molecular signature had a lower response to rituximab (anti-CD20 monoclonal antibody) compared with that to tocilizumab (anti-IL6R monoclonal antibody) although the exact mechanisms of response/nonresponse remain to be established. Here, in-depth histological/molecular analyses of R4RA synovial biopsies identify humoral immune response gene signatures associated with response to rituximab and tocilizumab, and a stromal/fibroblast signature in patients refractory to all medications. Post-treatment changes in synovial gene expression and cell infiltration highlighted divergent effects of rituximab and tocilizumab relating to differing response/nonresponse mechanisms. Using ten-by-tenfold nested cross-validation, we developed machine learning algorithms predictive of response to rituximab (area under the curve (AUC) = 0.74), tocilizumab (AUC = 0.68) and, notably, multidrug resistance (AUC = 0.69). This study supports the notion that disease endotypes, driven by diverse molecular pathology pathways in the diseased tissue, determine diverse clinical and treatment–response phenotypes. It also highlights the importance of integration of molecular pathology signatures into clinical algorithms to optimize the future use of existing medications and inform the development of new drugs for refractory patients.
This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.
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