During the study, patients who initially had an inadequate response to methotrexate received ≥15 mg oral methotrexate weekly plus 162 mg subcutaneous tocilizumab weekly, or 162 mg subcutaneous tocilizumab every two weeks. At Week 12 if patients had not achieved low disease activity (DAS28 ≤3.2), they could increase their dosing frequency from every two weeks to weekly. Patients who achieved DAS28-ESR ≤3.2 at Week 24 were randomized in a double-blind manner to receive either tocilizumab monotherapy or tocilizumab plus methotrexate through Week 52.
The primary outcome was the comparison of mean change in DAS28-ESR score from Weeks 24 to 40 between the tocilizumab monotherapy and tocilizumab plus methotrexate arms. The trial’s secondary outcomes included the proportion of patients who achieved DAS28 <2.6, DAS28 ≤3.2 and ACR20/50/70 responses at Weeks 40 and 52. Safety was also assessed, and 718 patients were enrolled.
At Week 24, 296 patients who had achieved DAS28-ESR ≤3.2 were randomized, with 148 receiving tocilizumab plus methotrexate and 148 receiving tocilizumab monotherapy. Early discontinuation in randomized patients was similar in both treatment groups. The mean patient age was 56 years, 75% of patients were women and the mean duration of RA of was 6.8 years. The mean DAS28-ESR was 6.3, and baseline characteristics were similar between the two groups.
DAS28 scores at Week 24 were similar in both treatment groups, but ACR responses were approximately 10% lower in the tocilizumab monotherapy group prior to methotrexate withdrawal (randomization). This study met its primary endpoint, demonstrating that discontinuing methotrexate in tocilizumab responders was non-inferior to continuing methotrexate.
In this study, the safety profile of subcutaneous tocilizumab was consistent with its known safety profile. No new safety signals were observed. Infection was the most common serious adverse event, occurring in 4.1% of patients.
Patients receiving combination therapy had a greater frequency of adverse events, serious adverse events and serious infections than those receiving tocilizumab monotherapy.
The results of this study show that patients receiving both tocilizumab plus methotrexate with low disease activity can discontinue methotrexate and preserve disease control.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- Tanaka Y, Takeuchi T, Umehara H, et al. Safety, pharmacokinetics and efficacy of E6011, an anti-Fractalkine monoclonal antibody, in a first-in-patient Phase 1/2 study on rheumatoid arthritis: 52-week results [abstract 1907]. Arthritis Rheumatol. 2017;69(suppl 10).
- 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 [abstract]. Arthritis Rheumatol. 2017;69(suppl 10).
