The analysis of the COMPACT trial sought to demonstrate noninferiority of tocilizumab alone versus tocilizumab plus methotrexate (MTX) in maintaining clinical response in patients with rheumatoid arthritis (RA) who achieve low disease activity (LDA) following treatment with tocilizumab plus MTX.
In this trial, patients with RA who were inadequate responders to MTX alone were initially treated with MTX (≥15 mg/week orally) plus subcutaneous tocilizumab 162 mg either weekly (qw; patients ≥100 kg) or every 2 weeks (q2w; patients <100 kg). Dose escalation from q2w to qw dosing was indicated in patients who had not achieved LDA (Disease Activity Score 28 [DAS28] ≤3.2) at week 12. Patients who achieved DAS28–erythrocyte sedimentation rate (DAS28-ESR) ≤3.2 at week 24 were randomized 1:1 to receive tocilizumab monotherapy or tocilizumab plus MTX until week 52 (double blind).
The primary outcome was comparison of the mean change in DAS28-ESR score from week 24 to week 40 between the tocilizumab monotherapy and tocilizumab plus MTX groups (noninferiority margin of 0.6). At week 24, patients (n = 294) were randomized to receive tocilizumab monotherapy (n = 147) or tocilizumab plus MTX (n = 147). The mean age of the study population was 55.5 years; the majority (74.8%) were female. The mean RA disease duration was 6.8 years, with a mean DAS28-ESR of 6.3. At week 24, prior to randomization, DAS28 scores were similar in both groups.
The primary efficacy analysis showed that, from week 24 to week 40, the mean change in DAS28 was 0.46 in the tocilizumab monotherapy group and 0.14 in the tocilizumab plus MTX group. A higher proportion of patients had DAS28-ESR worsening ≥1.2 in the tocilizumab plus MTX cohort versus the tocilizumab monotherapy cohort from week 24 to week 40 (28.6% vs 21.1%), which was similar at week 52 (29.9% vs 26.5%).
The authors concluded that patients receiving tocilizumab plus MTX who achieve LDA may discontinue MTX and maintain disease control with tocilizumab monotherapy.
Source: Kremer J, Rigby WFC, Singer N, et al. Sustained response following discontinuation of methotrexate in patients with rheumatoid arthritis treated with subcutaneous tocilizumab: results from a randomized controlled trial. Arthritis Rheumatol. 2017;69(suppl 10). Abstract 1905.