Subcutaneous Tocilizumab Superior to Methotrexate in Chinese Patients With RA

Subcutaneous tocilizumab (Actemra; Genentech) used alone or in combination with methotrexate is significantly more effective than methotrexate monotherapy in treating moderate to severe rheumatoid arthritis (RA) among Chinese patients, according to findings from a large-scale randomized clinical trial published in JAMA Network Open.

The double-blind, phase 3 trial randomized 340 adults with active RA who did not adequately respond to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to receive either tocilizumab plus methotrexate, tocilizumab plus placebo, or methotrexate plus palcebo. Tocilizumab 162 mg was administered subcutaneously once every other week, and methotrexate was administered orally between 10 mg and 25 mg once every week.

Tocilizumab was generally well tolerated, with no new safety concerns identified. | Image credit: yodiyim – stock.adobe.com

After 24 weeks, both of the tocilizumab treatment arms demonstrated markedly higher American College of Rheumatology 20% improvement (ACR20) response rates than the methotrexate group. Patients receiving the combination treatment had a 52.9% ACR20 response rate, followed by tocilizumab alone with 50%; methotrexate alone was linked to a response rate of only 25% (P < .001).

“The present study provides additional data on the efficacy and safety profile of subcutaneous tocilizumab monotherapy and combination therapy in patients with RA,” the authors added. “The response rate was similar with monotherapy or combination therapy, providing solid evidence for subcutaneous tocilizumab monotherapy.”

The study, which took place across 19 sites in China between 2017 and 2022, also included a 24-week extension phase and an 8-week safety follow-up. Patients whose disease activity score (DAS28) remained above 3.2 at week 24 were transitioned to open-label combination therapy, while those with controlled disease continued their original assigned regimen.

By week 48, patients who stayed on tocilizumab—either alone or with methotrexate—maintained or improved their clinical responses. Among patients initially treated with methotrexate alone who switched to combination therapy in the extension phase, ACR20, ACR50, and ACR70 response rates increased notably, suggesting prolonged tocilizumab exposure played a role in disease control.

While ACR70 responses at 24 weeks were not significantly different across groups, secondary measures such as DAS28 remission and low disease activity were consistently more favorable in the tocilizumab groups. Researchers also noted that hemoglobin levels numerically improved more with tocilizumab than with methotrexate alone.

Prior research has shown intravenous tocilizumab is both safe and effective when used with csDMARDs in patients with RA, including those who are methotrexate-naive or have not responded to TNF inhibitors—a finding also confirmed in Chinese populations.^2-4 Unlike TNF inhibitors, which typically require combination therapy, intravenous tocilizumab has shown strong efficacy even as monotherapy.¹ Subcutaneous tocilizumab has similarly proven effective and safe when used with csDMARDs, as demonstrated in both noninferiority trials comparing it with intravenous administration and superiority trials against placebo, according to the study authors.

Tocilizumab was generally well tolerated, with no new safety concerns identified. Adverse events (AEs) occurred in more than 70% of participants across all 3 groups, and most were mild to moderate in severity; the most common AE was upper respiratory tract infection. Serious AEs occurred slightly more often in the tocilizumab groups, impacting 9 patients on tocilizumab-methotrexate, 6 on tocilizumab-placebo, and 1 on methotrexate-placebo; grade 3 or higher AEs occurred in 13, 14, and 2 patients, respectively.

Regarding limitations of the study, the patient population being exclusively Chinese may limit generalizability, and the trial taking place over an extended period due to COVID-19 could have lead to some missed follow-ups. Additionally, methotrexate doses in the study were below the levels typically recommended by global rheumatology guidelines, which may have affected response rates in the methotrexate arm.

“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,” the authors wrote.

References

1. Liu T, Wang L, Zhang X, et al. Tocilizumab monotherapy or combined with methotrexate for rheumatoid arthritis: a randomized clinical trial. JAMA Netw Open. 2025;8(5):e2511095. doi:10.1001/jamanetworkopen.2025.11095
2. Burmester GR, Rigby WF, van Vollenhoven RF, et al. Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial. Ann Rheum Dis. 2017;76(7):1279-1284. doi:10.1136/annrheumdis-2016-210561
3. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67(11):1516-1523. doi:10.1136/ard.2008.092932
4. Lauper K, Nordström DC, Pavelka K, et al. Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration. Ann Rheum Dis. 2018;77(9):1276-1282. doi:10.1136/annrheumdis-2017-212845