Methotrexate discontinuation feasible in patients with stable PsA receiving tofacitinib
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Among patients with stable psoriatic arthritis receiving tofacitinib with methotrexate, some may be able to discontinue methotrexate without changes in disease activity or safety, according to data published in The Lancet Rheumatology.
“Methotrexate is frequently used as a first-line treatment for psoriatic arthritis, and recommendations suggest that the optimal initial dose reaches 25 mg/week,” Peter Nash, FRACP, of Griffith University, in Brisbane, Australia, and colleagues wrote. “In our experience, many patients do not respond to methotrexate, and have known tolerability issues, such as hepatotoxicity and gastrointestinal adverse events.”
“In patients with an inadequate response to methotrexate, some clinical guidelines have favored replacing methotrexate with an advanced therapy rather than adding to it,” they added. “However, the 2019 EULAR guidelines recommend continuing methotrexate with advanced therapies in patients who tolerate methotrexate well, and reducing the methotrexate dose in patients showing a good response to biological treatment, especially if there are concerns about toxicity.”
To assess the safety and efficacy of tofacitinib (Xeljanz, Pfizer) monotherapy following MTX withdrawal, Nash and colleagues conducted OPAL Balance, an open-label long-term extension study. Stretching 36 months, the study included adults with PsA from 124 centers across 16 countries. All included patients at participated in the previous qualifying phase 3 studies OPAL Broaden or OPAL Beyond. In addition, all received open-label tofacitinib 5 mg twice daily, with concomitant conventional synthetic disease-modifying antirheumatic drugs permitted, regardless of qualifying study treatment, as part of OPAL Balance.
The MTX-withdrawal sub-study of the OPAL Balance long-term extension was a phase 3, randomized, double-blind, placebo-controlled, parallel-group trial that lasted 12 months. This sub-study included 180 OPAL Balance participants who completed at least 24 months of tofacitinib treatment, including at least 3 months of stable, twice-daily doses of 5 mg, and were receiving 7.5 to 20 mg of MTX per week.
Between Oct. 30, 2017, and May 20, 2019, these participants were randomly assigned, with 90 receiving tofacitinib 5 mg twice daily alongside a placebo, and 89 patients treated with tofacitinib plus MTX. The last remaining participant was not treated due to a randomization error.
The coprimary endpoints were changes from sub-study baseline in PsA disease activity score (PASDAS) and health assessment questionnaire-disability index (HAQ-DI) at 6 months in all treated participants. The researchers assessed safety throughout. Neither superiority nor non-inferiority was tested.
According to the researchers, least squares mean (LSM) changes in PASDAS at 6 months were 0.23 (SE = 0.08) for tofacitinib plus placebo and 0.14 (SE = 0.08) for tofacitinib alongside MTX (treatment difference LSM = 0.09; 95% CI, –0.13 to 0.31). Meanwhile, changes in HAQ-DI were 0.04 (SE = 0.03) and 0.02 (SE = 0.03), respectively (treatment difference = 0.03; 95% CI, –0·05 to 0.1).
Rates of adverse events, discontinuations due to adverse events, adverse events of special interest, and laboratory changes were “generally similar” between treatment groups, the researchers wrote. However, liver enzyme elevations were more common among the tofacitinib-with-MTX group compared with those treated with tofacitinib alongside placebo. Worsening symptom flares — recorded as psoriatic arthropathy — were reported in one patient in the tofacitinib-plus-placebo group.
“The results of this sub-study provide further characterization of the efficacy of tofacitinib in patients with psoriatic arthritis,” Nash and colleagues wrote, “and suggest that some patients receiving tofacitinib 5 mg twice daily with background methotrexate who are in a stable disease state might be able to discontinue methotrexate to receive tofacitinib monotherapy, without an adverse effect on their overall disease activity or health-related quality of life.”
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