Study turns perception of combination therapy into reality
It had already been perceived by rheumatologists that methotrexate plus leflunomide was an effective combo for PsA, and this study reinforces those beliefs, Clementina López-Medina, MD, PhD, and colleagues from the University of Cordoba (Spain), write in an accompanying editorial.
They highlight this study’s notable strengths, one of which was defining “active disease” as two or more swollen joints, which opened the study up to a larger patient population. The editorialists also underline the confirmation that leflunomide plus methotrexate reduces both joint symptoms and skin involvement in this subset of patients, which had also been found in a previous study.
“Leflunomide is usually considered as a second-line option after methotrexate is unsuccessful,” they note, “despite the fact that methotrexate did not show superiority over placebo in previous trials.”
The editorialists were not surprised that the combination therapy was more toxic than the monotherapy. Rheumatologists could use these data to individualize treatment accordingly, they write, while keeping an eye on “gastrointestinal disturbances.”
Overall, Dr. López-Medina and colleagues say that the study results should “be considered not only in daily clinical practice but also in the development of future recommendations.”
Leflunomide: Forgotten no longer, at least for PsA
“I think we probably underutilize leflunomide,” Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, told this news organization. “Sometimes medicines get ‘old,’ for lack of a better term, and fall a little bit of out of favor, sometimes unnecessarily. Leflunomide falls into that category. Because it’s older, it doesn’t get as much buzz as what’s new and shiny.
Dr. Arthur Kavanaugh
“I was not surprised by the results on the joints,” he said, “because we know from previous studies that leflunomide works in that regard. What did surprise me is that the skin got better, especially with the combination.”
Regarding the side effects for the combination therapy, he commended the authors for limiting potential uncertainty by using such a high dose of methotrexate.
“By going with a dose of 25 mg [per week], no one can say, ‘They pulled their punches and methotrexate monotherapy would’ve been just as good if it was given at a higher dose,’ “ he said. “And they also used leflunomide at a high dose. It makes you wonder: Could you use lower doses, and do lower doses mean fewer lab test abnormalities? This positive study does lend itself to some other permutations in terms of study design.
“Even though this was a small study,” he added, “it brings us right back to: We should really consider leflunomide in the treatment of PsA.”
The authors acknowledge their study’s limitations, including the fact that it was conducted in a single country and the absence of a nontreatment placebo group. They also note the higher percentage of women in the methotrexate plus leflunomide group, “which might have lowered the treatment response and increased the adverse event rate, resulting in bias.”
The study was funded by a Regional Junior Researcher Grant from Sint Maartenskliniek. The authors reported numerous potential conflicts of interest, including receiving payment, research grants, and consulting and speaker fees from various pharmaceutical companies.
A version of this article first appeared on Medscape.com.