Patients with rheumatoid arthritis may experience slower resolution of swelling in the wrist and second and third metacarpophalangeal joints compared with most other joints following the initiation of biologic or targeted synthetic disease-modifying antirheumatic drugs.
Investigators analyzed data from the Swiss Clinical Quality Management in Rheumatic Diseases registry to determine whether treatment response depended on joint location. The primary analysis included 598 bio-naive patients with rheumatoid arthritis who initiated a tumor necrosis factor (TNF) inhibitor and had at least one swollen joint at treatment initiation. Secondary analyses included 1,942 patients who initiated abatacept, interleukin (IL)-6 receptor inhibitors, Janus kinase (JAK) inhibitors, rituximab, or TNF inhibitors, regardless of previous biologic exposure. The patients were followed for up to 2 years. The primary outcome was time to first resolution of joint swelling, and secondary outcomes included time to resolution of joint tenderness and comparisons of joint-specific responses across treatment classes.
Among the patients receiving their first TNF inhibitor, nearly all joints demonstrated faster resolution of swelling compared with the wrist. The second and third metacarpophalangeal joints showed similarly slow rates of improvement. The knee also demonstrated relatively slow resolution in some analyses. Most joints resolved during the first 6 to 12 months of follow-up, and recurrent synovitis occurred most often in the wrist, second and third metacarpophalangeal joints, proximal interphalangeal joints of the second and third fingers, and the knee.
The same joint-specific response pattern was observed among patients treated with abatacept, IL-6 receptor inhibitors, JAK inhibitors, rituximab, and TNF inhibitors. Resolution of joint tenderness mirrored the findings for joint swelling. Additional analyses adjusting for body mass index, methotrexate use, occupation, and body side produced similar results, although right-sided joints resolved more slowly compared with left-sided joints.
When the investigators directly compared treatment classes in bio-naive patients, they found no statistically significant differences in joint-specific responses between the therapies. The consistent response pattern across treatment mechanisms suggested that slower improvement was associated with joint location rather than with a specific biologic or targeted synthetic agent.
The findings may have implications for treatment assessment because inflammation involving the wrist and second and third metacarpophalangeal joints appeared to resolve more slowly compared with inflammation in most other joints. They also suggested that bridging intra-articular steroid injections could be considered when these joints remain inflamed while patients await the full therapeutic effect of systemic therapy, although this approach was not evaluated in the study.
The study had several limitations. Its observational design did not support causal inference, synovitis was assessed clinically without ultrasound or magnetic resonance imaging confirmation, and the primary analyses excluded patients who discontinued treatment prior to joint swelling resolved. Residual confounding may have remained despite statistical adjustment, and routine registry assessments did not include foot joints.
Overall, the findings suggested that physicians may need to allow more time to evaluate treatment response when the wrist or second and third metacarpophalangeal joints remain involved following initiation of biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARD).
"In conclusion, the wrist, [second and third metacarpophalangeal] joints respond more slowly than other joints following initiation of a [biologic or targeted synthetic] DMARD, indicating that overall treatment response should be evaluated at a later time point when these joints are involved," wrote lead study author Annik Steimer, of the Department of Rheumatology at the University Hospital Zurich at the University of Zurich in Switzerland, and colleagues. "In addition, bridging intra-articular steroid injections targeting these specific joints may be considered at treatment initiation of a [biologic or targeted synthetic] DMARD to help manage persistent local inflammation," they concluded.
The study was supported by the MLR Foundation. Full disclosures of the study authors are available in the study.
Source: RMD Open