medwireNews: The addition of leflunomide to methotrexate monotherapy results in significant improvements in disease activity among people with active psoriatic arthritis (PsA), suggest findings from the COMPLETE-PsA trial.
However, the combination of both drugs was less well tolerated and associated with higher rates of treatment discontinuation than methotrexate monotherapy, say Michelle Mulder (Sint Maartenskliniek, Nijmegen, the Netherlands) and co-investigators.
As reported in The Lancet Rheumatology, mean PASDAS improved from 4.9 points at baseline to 3.1 points at week 16 among the 39 participants who were randomly assigned to receive methotrexate (15 mg/week for 4 weeks followed by 25 mg/week thereafter if well tolerated) plus leflunomide (20 mg/day with dose reduction to 10 mg/day if required).
By comparison, mean PASDAS improved from 4.9 to 3.7 points among the 38 patients given methotrexate plus placebo, giving a significant between-group difference of 0.6 points favoring the combination.
Participants in the methotrexate plus leflunomide arm also had significantly higher rates of PASDAS low disease activity (≤3.2 points) than those in the methotrexate monotherapy arm (59 vs 34%), as well as significantly greater improvements in median swollen joint counts and physician global VAS scores. Mulder and team note that “most skin or nail measures […] were significantly better” among patients treated with the combination.
In all, 10 participants in the combination group and three of those in the methotrexate alone group permanently discontinued treatment due to adverse events (AEs). The most frequently reported AEs were nausea and vomiting, affecting 44% versus 28% of people in the combination and monotherapy arms, respectively, followed by tiredness (23 vs 33%) and elevated alanine aminotransferase (31 vs 18%).
The investigators say that rates of “mostly mild” AEs were generally higher in the combination than the monotherapy arm, with the largest between-group difference seen for altered bowel habits (26 vs 8%). Three participants treated with methotrexate plus leflunomide experienced serious AEs, including one case of severe infection, drug reaction, or both that was considered potentially treatment-related, and two serious AEs that were deemed unrelated to treatment.
Discussing the trial findings in a linked comment, Clementina López-Medina (Maimonides Biomedical Research Institute of Cordoba, Spain) and colleagues say that COMPLETE-PsA “provides objective and evidence-based reasons to use methotrexate plus leflunomide for patients with psoriatic arthritis.”
They add: “The results of this study will help rheumatologists to individualise treatment and closely monitor potential side-effects during the first weeks of therapy, with special regard to gastrointestinal disturbances such as abdominal pain, nausea or vomiting, and altered bowel habits.”
López-Medina and co-authors note that in contrast to trials of biologic DMARDs, which usually require polyarticular involvement, COMPLETE-PsA defined active disease as two or more swollen joints.
“This definition allows evaluation of methotrexate plus leflunomide in a larger patient population, including those with oligoarticular disease, which is the most frequent clinical presentation seen in rheumatology clinics,” they explain.
The commentators conclude that the COMPLETE-PsA results “should be considered not only in daily clinical practice but also in the development of future recommendations.”
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