IMPORTANCE: Treatment options are needed for patients with rheumatoid arthritis (RA) who experience inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The efficacy and safety profiles of subcutaneous tocilizumab monotherapy, tocilizumab combined with methotrexate, and methotrexate alone have not yet been evaluated in the same large-scale study. OBJECTIVE: To evaluate the efficacy and safety of subcutaneous tocilizumab monotherapy, tocilizumab-methotrexate, and methotrexate alone for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, large-scale phase 3 randomized clinical trial was conducted at 19 sites in China from July 2017 through August 2022, with a 24-week double-blind treatment phase, a 24-week extension phase, and 8 additional weeks of safety follow-up. The trial included adults (aged 18-70 years) who had moderate to severe active RA and had experienced an inadequate response to csDMARDs. INTERVENTIONS: In the 24-week double-blind treatment phase, patients were randomized 2:2:1 to tocilizumab-methotrexate, tocilizumab-placebo, or methotrexate-placebo. In the 24-week extension phase, patients who achieved a disease activity score using 28 joints (DAS28) of up to 3.2 at week 24 continued their double-blind phase treatment
those with scores greater than 3.2 received open-label tocilizumab-methotrexate. Tocilizumab (162 mg) was administered subcutaneously once every 2 weeks
oral methotrexate (10-25 mg) was administered once weekly. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was week 24 American College of Rheumatology 20% improvement (ACR20) response. Long-term efficacy analysis was carried out at week 48
safety was monitored for 56 weeks. RESULTS: This study included 340 patients (mean [SD] age, 47.5 [11.7] years
294 women [86.5%]). A total of 136 patients were randomized to tocilizumab-methotrexate, 136 to tocilizumab-placebo, and 68 to methotrexate-placebo. The week 24 ACR20 response rate was significantly greater with tocilizumab-methotrexate and tocilizumab-placebo vs methotrexate-placebo (72 of 136 [52.9%] vs 17 of 68 [25.0%]
difference, 27.9 percentage points [95% CI, 14.7-41.2 percentage points]
P <
.002
and 68 of 136 [50.0%] vs 17 of 68 [25.0%]
difference, 25.0 percentage points [95% CI, 11.7-38.3 percentage points]
P <
.002). The week 48 analysis demonstrated improved or maintained efficacy during the extension period in patients who continued double-blind tocilizumab-placebo or tocilizumab-methotrexate treatment
patients who switched from double-blind tocilizumab-placebo or tocilizumab-methotrexate to open-label tocilizumab-methotrexate had improved disease status. No new safety signals were observed for tocilizumab. CONCLUSIONS AND RELEVANCE: In this large-scale randomized clinical trial evaluating subcutaneous tocilizumab in Chinese patients, subcutaneous tocilizumab, either as monotherapy or combined with methotrexate, demonstrated superior efficacy to methotrexate monotherapy and was well tolerated. More research data in ethnically and regionally more diverse populations may be needed to further confirm the efficacy and safety of subcutaneous tocilizumab, especially as monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03155347
China Center for Drug Evaluation Identifier: CTR20170141.