Arundathi Jayatilleke, MD
Predicting severe disease is of great importance in rheumatoid arthritis (RA), ideally to establish which poor prognostic factors allow for early aggressive and targeted treatment for a subset of patients. In a post hoc analysis of the AGREE study by Durez and colleagues , 509 treatment-naive patients randomized to either methotrexate or methotrexate with abatacept were evaluated for predictors of joint damage and disease activity. Baseline swelling in the knee, temporomandibular joint (TMJ), elbow, and wrist was correlated with severe disease activity as well as tender and swollen joint counts, whereas baseline swelling at the second metacarpophalangeal joint was correlated with erosive disease. Overall, remission rates were better in patients with baseline wrist, TMJ, elbow, and knee swelling treated with combination therapy vs methotrexate alone, suggestive of a better response to more aggressive therapy. Further studies of patients with RA with poor prognostic factors would be helpful.
Laboratory biomarkers can also serve as prognostic indicators for patients with RA. Based in part on the association of obesity and lower rates of remission in people with RA, Baker and colleagues investigated the possible association of adipocytokines and disease activity in a cohort study of over 1200 patients with Disease Activity Score for Rheumatoid Arthritis (DAS28) > 3.2 enrolled in the Veterans Affairs RA registry. Of these, about 800 achieved low disease activity while the remainder did not. Interestingly, obesity was not a baseline characteristic associated with disease activity, though chronic obstructive pulmonary disease, heart failure, and mood disorders were. Baseline adipocytokine levels on average did not differ between the two groups, though higher baseline adiponectin and leptin levels (based on quartile) were associated with a lower likelihood of achieving low disease activity. Interestingly, this change did not increase progressively with higher quartile. Because these are baseline levels and were not tracked prospectively with medication use, it is difficult to assess the importance of this finding. The association may not reflect a causative relationship but may be affected by medications or disease duration. However, it appears worthwhile investigating in therapy-naive patients as well as those being observed with treatment.
Finally, with respect to novel therapeutic regimens, Fleischmann and colleagues report the results of a multicenter randomized clinical trial of a Bruton tyrosine kinase inhibitor, elsubrutinib, alone or in combination with the Janus kinase (JAK) inhibitor upadicitinib in the treatment of 242 patients with RA. At the end of 12 weeks, DAS28 with C-reactive protein scores were not measurably lower in patients treated with elsubrutinib at different doses. In addition, patients receiving the combination therapy of 15 mg upadicitinib with the highest dose of elsubrutinib (60 mg) did not have greater DAS28 improvement than patients treated with upadicitinib alone, suggesting a lack of synergistic effect. Short-term safety data does not suggest significant differences. Though this combination is also being investigated in systemic lupus erythematosus, it is not clear that the combination of two targeted synthetic disease-modifying antirheumatic drugs is feasible in RA, nor that long-term safety concerns would make it advisable.