"Our findings increase the knowledge on the seemingly superior efficacy of leflunomide and methotrexate combination therapy versus methotrexate monotherapy in psoriatic arthritis," Dr. Michelle Mulder of Sint Maartenskliniek, Nijmegen in the Netherlands told Reuters Health by email. "Clinicians might consider using this combination in either a step-down or -up approach depending on the situation."
"Although our hypothesis was that the addition of leflunomide to methotrexate would be superior to methotrexate monotherapy, the difference in effectiveness still surprised us," she said. "Particularly striking was that (although) a large percentage of the included patients had limited oligoarticular disease, we still found that almost twice the patients reached minimal disease activity and (low) psoriatic arthritis disease activity scores (PASDAS) in the methotrexate plus leflunomide group."
As reported in The Lancet Rheumatology, Dr. Mulder and colleagues randomly assigned 78 patients (median age, 55; 64%, men) with psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) to methotrexate plus leflunomide or methotrexate plus placebo.
Patients were stratified by high disease activity (PASDAS score, 5.4 or more). Both groups received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter, combined with two leflunomide 10 mg tablets once per day or two placebo tablets
The primary outcome was the between-group difference in mean PASDAS at week 16, adjusted for baseline PASDAS.
Combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3.1 vs. 3.7).
Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group.
The most frequent adverse events were nausea or vomiting (44% vs. 28%), fatigue (23% vs. 33%) and elevated alanine aminotransferase (31% vs. 18%).
There were no deaths.
Dr. Mulder said, "Our research underscores that conventional disease-modifying antirheumatic drugs (DMARDs) might still have a role to play next to biological and targeted synthetic DMARDs and should be included in treatment strategy trials."
Coauthor Dr. Philip Helliwell of the University of Leeds, UK, added in a separate email, "Leflunomide combined with methotrexate is more efficacious than methotrexate alone but the combination is likely less effective than methotrexate plus a biologic. In the UK, starting the combination will be more efficacious than the single drug (methotrexate) and will result in a faster path to biologics, should the combination not work for the patient."
Dr. Clementina Lopez-Medina of the Maimonides Biomedical Research Institute of Cordoba in Spain, coauthor of a related editorial, commented in an email to Reuters Health, "This study provides objective and evidence-based reasons to use methotrexate plus leflunomide for patients with psoriatic arthritis. Based on the positive joint and skin involvement results, this combination should be considered - if well tolerated - in the management of patients with psoriatic arthritis."
"The results should be considered not only in daily clinical practice, but also in the development of future recommendations," Dr. Lopez-Medina concluded.
SOURCE: https://bit.ly/3ik1aoM and https://bit.ly/3CTeeuG The Lancet Rheumatology, online February 28, 2022.
By Marilynn Larkin
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