For patients with rheumatoid arthritis (RA) who respond to subcutaneous tocilizumab, discontinuing methotrexate may be an option and offer an alternative to patients who cannot tolerate or prefer not to take methotrexate.
Explore this issueOctober 2018
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“This is one of the first studies showing that methotrexate may be discontinued in a cohort of patients with a biologic agent without experiencing a significant predefined disease flare,” says Joel Kremer, MD, PFAFF Family Professor of Medicine, Albany Medical College, and director of research, The Center for Rheumatology, Albany, N.Y., and lead author of the first controlled study to examine discontinuing methotrexate in patients receiving subcutaneous tocilizumab for RA.
Treatment of RA commonly includes combination therapy of methotrexate with a biologic agent, with data showing combination therapy is more effective, particularly when methotrexate is combined with tumor necrosis factor (TNF) inhibitors. Data have shown, however, similar efficacy with intravenous tocilizumab either combined with methotrexate or as monotherapy. The study by Kremer et al. builds on this by finding subcutaneous tocilizumab as monotherapy is noninferior to combined therapy with methotrexate.
The study “supports the concept that tocilizumab can be used as a monotherapy,” says Michael Weinblatt, MD, John R and Eileen K. Riedman Professor of Medicine, Harvard Medical School and R. Bruce and Joan M. Mickey Distinguished Chair in Rheumatology, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston. “In patients who achieve the targeted goal of low disease activity or remission on the combination of methotrexate and tocilizumab, many patients can maintain low disease activity with abrupt discontinuation of methotrexate.”
A Closer Look at the Study
In the multicenter, double-blind study, 294 patients with RA were randomized at Week 24 to subcutaneous tocilizumab monotherapy (n=147) or methotrexate plus subcutaneous tocilizumab (n=147) for 52 weeks. Patients were among the total 718 patients enrolled in the study who experienced an inadequate response to methotrexate and received combination methotrexate and tocilizumab (162 mg subcutaneously) for 24 weeks. At 24 weeks, all patients (n=294) who had achieved low disease activity per a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of <3.2 were randomized to the two treatment groups.
To test the noninferiority (margin of 0.6) of discontinuing methotrexate in this patient cohort, the investigators used a primary outcome measure of the mean change in the DAS28-ESR from Week 24 to Week 40 between the two treatment groups.