Subclinical synovitis: let's discuss prognosis before treatment

Advances in the diagnosis and treatment of rheumatoid arthritis has transformed its perception from a progressive debilitating illness to a manageable chronic condition. One important step in this achievement was a shift in treatment strategy, focusing on intervention as early as possible. This idea of early intervention has even extended to the predisease realm to block the onset of clinical arthritis, exemplified by trials of disease-modifying antirheumatic drugs (DMARDs) in individuals at risk of rheumatoid arthritis (PRAIRI and TREAT EARLIER). 1 Gerlag DM Safy M Maijer KI et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2019; 78: 179-185 Crossref PubMed Scopus (143) Google Scholar , 2 Krijbolder DI Verstappen M van Dijk BT et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022; 400: 283-294 Summary Full Text Full Text PDF PubMed Google Scholar Findings from these trials show some benefits for treating individuals at risk of developing rheumatoid arthritis, such as the delay in the onset of clinical disease in the PRAIRI trial 1 Gerlag DM Safy M Maijer KI et al. Effects of B-cell directed therapy on the preclinical stage of rheumatoid arthritis: the PRAIRI study. Ann Rheum Dis. 2019; 78: 179-185 Crossref PubMed Scopus (143) Google Scholar and improvement in pain and the quality of life observed in the TREAT EARLIER trial. 2 Krijbolder DI Verstappen M van Dijk BT et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022; 400: 283-294 Summary Full Text Full Text PDF PubMed Google Scholar One common pitfall in both of these trials however was a relatively low proportion—ie, less than half—of individuals developing clinical arthritis in the placebo groups. Therefore identifying high-risk individuals with serological abnormalities or inflammatory pain, or both, should remain a focus since individuals with the highest risk would theoretically be the most likely to benefit from treatment for secondary prevention at an affordable risk of treatment-related harm. Our current conception of risk stratification in individuals at risk of rheumatoid arthritis without clinical arthritis builds upon three primary components, namely autoantibodies, musculoskeletal symptoms, and subclinical inflammation of the synovial membranes detected via musculoskeletal ultrasonography or MRI. 3 Mankia K Siddle H Di Matteo A et al. A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis. RMD Open. 2021; 7e001768 Crossref PubMed Scopus (10) Google Scholar Each of these components includes characteristics yet to be further examined for a better understanding of their prognostic role; such as the titre, breadth, or post-translational modification of autoantibodies as well as the quality, extent, and course of symptoms and subclinical inflammation. Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort studyIn individuals who were anti-CCP-positive, subclinical synovitis disappeared in approximately half of the participants by 12 months and was associated with the presence of good prognostic factors. Subclinical synovitis should be interpreted in the context of these additional factors. Full-Text PDF Open Access