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Is Methotrexate Necessary with Tofacitinib?

Rheumatoid arthritis patients taking tofacitinib (Xeljanz) plus methotrexate who achieved low disease activity (LDA) may be able to withdraw from the latter agent without significant worsening of disease activity, a researcher reported at EULAR 2019 in Madrid.

After 24 weeks of treatment, patients treated with tofacitinib monotherapy had a Disease Activity Score-28 for Rheumatoid Arthritis with ESR (DAS28-ESR) that was 0.30 points higher than the combination arm, a difference that fell within the prespecified 0.60-point boundary for determining non-inferiority, said Stanley Cohen, MD, of the University of Texas Southwestern Medical Center in Dallas.

"Most patients with rheumatoid arthritis [RA] with moderate to high disease activity receiving tofacitinib modified-release 11 mg once daily plus methotrexate who achieve low disease activity and cannot tolerate or prefer not to use methotrexate may discontinue it without significant worsening of disease activity or unexpected safety issues," Cohen said at the European Congress on Rheumatology, the European League Against Rheumatism (EULAR) annual meeting.

Cohen added that many of his patients who achieve LDA status and are maintained on a regimen with methotrexate are "voting with their feet" and are discontinuing the drug with or without physician support.

Cohen and colleagues enrolled individuals who were treated for active RA with the combination therapy for 24 weeks, before achieving LDA. Patients were then randomized to receive tofacitinib modified-release 11 mg daily and methotrexate or tofacitinib 11 mg daily plus placebo, and were followed for another 24 weeks. 

The researchers assigned 266 patients to the combination therapy arm and 264 patients to the placebo arm. At the end of the trial, 247 and 238 patients remained in the trial, respectively.

More than three-fourths of the patients were women with a mean age of 56 and a mean RA diagnosis of 9 years; 85% were white. The majority of patients (60%) were treated in Europe, while one-third were treated in the U.S.

About 40% of patients in both arms experienced adverse events (AEs), specifically 10 patients in the monotherapy arm who experienced serious AEs, as did five patients in the combination therapy arm. 

"These data are clinically meaningful as they further support the dosing and regimen options of tofacitinib for managing patients with rheumatoid arthritis," Cohen said. "These results may be used to inform treatment guidelines regarding optimal approaches for discontinuation of methotrexate in patients with rheumatoid arthritis." 

John Isaacs, MBBS, PhD, chair of the EULAR Abstract Selection Committee, told MedPage Today that "I would like to see more data about those patients who did need methotrexate and I expect we will see that subsequently. A lot of us, when we switch to a biologic, tend to keep our patients on methotrexate, especially if our patients are already on it. But a lot of the patients on methotrexate don't like it. Even though the phase III studies suggest that monotherapy is effective, a lot of us still like to use a combination for various reasons." 

Isaacs said that if he had a patient who had LDA status and was doing well, but was unhappy on methotrexate, "I think this study will help us make the decision of whether methotrexate can be withdrawn in these patients." 

The study was supported by Pfizer. Some co-authors are company employees.

Cohen disclosed relevant relationships with AbbVie, Eli Lilly, Genentech, Gilead, and Pfizer.

Isaacs disclosed relevant relationships with Pfizer, Abbvie, Roche, Galvani, Merck, Gilead, Eli Lilly, Amgen, Janssen, Celltrion, and the NAPP.

Source Reference: Cohen S, et al "Methotrexate withdrawal in patients with rheumatoid arthritis who achieve low disease activity with tofacitinib modified release 11 mg once daily + methotrexate: A randomised non-inferiority Phase 3B/4 study" EULAR 2019; Abstract LB0004.

The author has no conflicts of interest to disclose related to this subject

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