In patients with tocilizumab (TCZ)-treated rheumatoid arthritis (RA), low disease activity can be maintained following the discontinuation of concomitant methotrexate, according to research published in Modern Rheumatology.
For this multicenter, open-label, uncontrolled, prospective, 64-week study, the researchers sought to evaluate the safety and efficacy of methotrexate discontinuation in patients with sustained low-disease-activity RA. Patients were receiving TCZ plus methotrexate combination therapy and had a score of 10 or lower on the Clinical Disease Activity Index (CDAI) for 12 weeks or longer.
The investigators analyzed data from the first 36 weeks of the 64-week study. Per treatment protocol, at week 0, methotrexate dosing frequency was decreased from weekly to bi-weekly; the dose of this treatment was not changed. At 12 weeks, following maintenance of low disease activity, methotrexate was discontinued, while TCZ and conventional synthetic disease-modifying antirheumatic drugs were continued at a stable dose.
Data from all patients (n=53) were included in the safety analysis, whereas data from 49 patients were included in the efficacy analysis. In total, 12 patients experienced a disease flare by week 36. Among them, 3 and 6 patients with CDAI scores of greater than 10 and less than or equal to 10, respectively, received rescue treatment. At 12, 24, and 36 weeks, the proportions of patients who maintained low disease activity were 87.8%, 81.6%, and 75.5%, respectively.
A larger proportion of patients undergoing subcutaneous TCZ therapy maintained low disease activity at week 36 compared with intravenous TCZ therapy (82% vs 72%). Additionally, a larger proportion of patients not receiving glucocorticoid therapy maintained low disease activity, compared with those who were receiving glucocorticoids (80% vs 64%). However, univariate logistic regression analyses found that TCZ administration route and glucocorticoid use had “no significant impact” on the maintenance of low disease activity at week 36.
In terms of safety, 58% of patients reported 54 adverse events, and 9% of patients reported 5 serious adverse events. “Safety analyses revealed no unexpected TCZ safety issues,” the researchers noted.
Study limitations include the open-label nature of the study, the lack of a control group, and a limited observation period. Additionally, the study focused on Japanese patients with RA, potentially limiting generalizability.
“The results of the present study demonstrate that discontinuation of [methotrexate] is clinically feasible for maintaining low disease activity … [D]iscontinuation of [methotrexate] may be beneficial from the perspective of reducing [adverse events].”
This clinical trial was supported by Chugai Pharmaceutical Co., Ltd. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Asai S, Hayashi M, Hanabayashi M, et al. Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab: an interventional study [published online August 7, 2019]. Mod Rheumatol. doi: 10.1080/14397595.2019.1641934