Arthritis & Rheumatology最新文献

For a searchable version of these abstracts, please visit www.acrabstracts.org.

For a searchable version of these abstracts, please visit www.acrabstracts.org.

Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA).

Methods: In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open-label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months.

Results: Sixty-five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo (P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality-of-life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection.

Conclusion: In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

Objective: The pharmacodynamic effects of litifilimab on type I interferon (IFN) response and correlations with clinical outcomes were investigated in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

Methods: Participants from part A (SLE) or part B (CLE with or without SLE) of the randomized phase 2 LILAC trial who received litifilimab (at 50 mg, 150 mg, or 450 mg) or a placebo were included. IFN gene signature (IFNGS) scores were assessed from whole-blood samples using a 22-gene panel in 120 and 131 participants (parts A and B, respectively). IFNα and other IFN-regulated cytokine concentrations were measured in serum in 112 and 131 participants (parts A and B, respectively).

Results: Most participants were IFNGS-high at baseline (79-91%), and no baseline IFNGS-low participant results were reported. In IFNGS-high participants, litifilimab induced rapid, significant (nominal P < 0.05), and sustained reductions in IFNGS scores and IFNα concentrations versus a placebo for litifilimab at 450 mg in part A and for litifilimab at 150 mg and 450 mg in part B. In part A, IFNα reductions with litifilimab were correlated with clinical response measures. In part B, dose-response relationships for IFNGS score and IFNα concentration were observed, similar to those for disease activity measured with the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score.

Conclusion: Administration of litifilimab resulted in reductions in both IFNGS scores and IFNα concentrations, pharmacodynamic effects that correlated with clinical responses. These findings support the mechanism of action of litifilimab and its continued evaluation in larger studies of patients with SLE or CLE.

Objective: Abnormalities in pain regulatory mechanisms are common in patients with rheumatoid arthritis (RA). We investigated whether pain sensitization changes after treatment with a disease-modifying antirheumatic drug (DMARD) and explored associations between changes in pain sensitization and disease activity.

Methods: We included 182 participants with active RA initiating/switching DMARD therapy who were observed for 12 weeks. To assess pain sensitization, participants underwent quantitative sensory testing (QST), including pressure pain thresholds (PPTs) at multiple anatomic sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). RA disease activity was measured using the Disease Activity Score 28 with C-reactive protein (DAS28-CRP) and its components. Mean changes in QST measures were examined from baseline to 12 weeks, and associations between QST and disease activity measures were explored using Pearson correlation coefficients and adjusted linear regression analyses.

Results: PPTs significantly increased (improved) at multiple anatomic sites following 12 weeks of DMARD therapy. No significant changes were observed in TS or CPM. Increased PPTs at multiple anatomic sites were associated with reductions in DAS28-CRP, swollen joint count, tender joint count, and improvements in patient global assessment. No significant associations were observed between TS, CPM, and disease activity.

Conclusion: Pain sensitivity improved after 12 weeks of DMARD therapy. These improvements were associated with reductions in disease activity.