Methotrexate (MTX) is often combined with biologics for the treatment of rheumatoid arthritis (RA); however, it may be discontinued due to intolerance or to reduce medication burden. The current analysis of the COMP-ACT trial sought to demonstrate noninferiority of tocilizumab monotherapy versus tocilizumab plus MTX in maintaining clinical response in patients with RA who achieve low disease activity (LDA) following treatment with tocilizumab plus MTX.
In this trial, US patients with RA who were inadequate responders to MTX alone were initially treated with MTX (≥15 mg/week orally) plus subcutaneous (SC) 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 measured was comparison of the mean change in DAS28-ESR score from weeks 24 to 40 between the tocilizumab monotherapy and tocilizumab plus MTX groups (noninferiority margin of 0.6). Secondary outcomes included the proportion of patients achieving DAS28 <2.6, DAS28 ≤3.2, and 20%/50%/70% improvement in American College of Rheumatology (ACR) improvement criteria (ACR20/ACR50/ACR70) responses at weeks 40 and 52, and safety.
At week 24, patients (n = 294) were randomized to receive tocilizumab monotherapy (n = 147) or tocilizumab plus MTX (n = 147). Baseline characteristics were balanced between treatment groups. The mean age of the study population was 55.5 years; the majority were female (74.8%). 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 weeks 24 to 40, the mean change in DAS28 was 0.46 in the tocilizumab monotherapy group and 0.14 in the tocilizumab plus MTX group (difference of 0.318; 95% confidence interval, 0.045-0.592). 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%). A higher percentage of patients in the tocilizumab plus MTX group achieved DAS28-ESR LDA versus the monotherapy group at weeks 40 and 52.
The safety analysis showed no new safety signals. The safety profile of SC tocilizumab was consistent with the known safety profile. The incidence of adverse events (AEs; events per 100 patient-years [PY], 238 and 308, respectively), serious AEs (events per 100 PY, 238 and 308, respectively), and serious infections was higher in the cohort that received tocilizumab plus MTX versus the tocilizumab monotherapy cohort. Infection was the most common serious AE, with a rate per 100 PY of 3.25 in the monotherapy cohort and 4.42 in the tocilizumab plus MTX cohort. There were no cases of anaphylaxis reported in the study; patients (n = 10) developed treatment-induced anti-tocilizumab antibodies during the tocilizumab plus MTX treatment (before week 24).
The results of this study met its primary end point by demonstrating that, in patients who achieved LDA with tocilizumab plus MTX, tocilizumab monotherapy was noninferior to tocilizumab plus MTX. The authors concluded that patients receiving tocilizumab plus MTX who achieve LDA may discontinue MTX and maintain disease control with tocilizumab monotherapy.
Kremer J, et al. ACR 2017. Abstract 1905.