NEW YORK (Reuters Health) – A combination of two approved drugs, leflunomide and hydroxychloroquine, was safe and generated a clinical response in a phase 2a trial for Sjogren's syndrome.
For the 24-week trial, Dr. Joel Adrianus Gijsbert van Roon of Utrecht University Medical Center and colleagues randomized 20 women and one man to 20 mg of leflunomide and 400 mg of hydroxychloroquine daily, and eight women to placebo. One patient in the placebo group required high doses of prednisone to treat polymyalgia rheumatica at week 13 and was excluded from the primary analysis.
The patients had a European League Against Rheumatism Sjogren's Disease Activity Index (ESSDAI) score of 5 or more, and a lymphocytic focus score of 1 or more in biopsies samples from the lip salivary glands. The average duration of the disease was approximately eight years.
The primary endpoint was the difference between groups in the change in ESSDAI scores from 0 to 24 weeks, adjusted for baseline ESSDAI score.
As reported in The Lancet Rheumatology, the mean difference in adjusted ESSDAI score was -4.35 in the leflunomide-hydroxychloroquine group compared to placebo.
No serious adverse events occurred in the intervention group, while two occurred in the placebo group (hospital admission for pancreatitis and hospital admission for nephrolithiasis).
The most common adverse events in the intervention group were gastrointestinal distress (52% vs. 25% for placebo); moderate transient increases in alanine aminotransferase (48% vs. 13%); and short episodes of general malaise and tremors (43% vs. 13%).
Dr. Astrid Rasmussen of the Oklahoma Medical Research Foundation in Oklahoma City, author of a related editorial, told Reuters Health by email that the trial "addresses the unmet need (for) treatment … that goes beyond of improving local dryness. "
"The most interesting part of the proposal is that, in addition to achieving clinically relevant improvement in disease activity and wellness measures, it does so by reusing old medications," he said. "Both hydroxychloroquine and leflunomide have been used in the treatment of rheumatic diseases for many years, and their safety profile has been well proven."
"Now, this group of researchers is translating the observed synergy of the two drugs in vitro into possible new therapeutic strategies for Sjogren's syndrome," he said. "While this excites enthusiasm, it is still too early to know whether the results derived from a small proof-of-concept trial will be replicated in larger multi-center randomized controlled trials. Until then, it is premature to apply this in clinical practice."
Dr. Andres Pinto, Sjogren's syndrome expert, chair and professor in the Department of Oral and Maxillofacial Medicine and Diagnostic Sciences at Case Western Reserve University in Cleveland, Ohio, commented by email: "This study uses two medications that independently have some utility in the primary Sjogren "The strength of the study, in my opinion, is the measurement of clinical, biological, histological and proteomic markers. More research is still needed to assess efficacy and long-term safety. "
"I liked the efforts to discern an inflammatory endotype, that is, a group of biomarkers, that could potentially predict the response to therapy," he told Reuters Health.
That said, he added, "I would like to see a phase 3 study to confirm these preliminary findings. This study is based on less than 30 patients."
Dr. van Roon did not respond to requests for comment.
SOURCE: https://bit.ly/2UKqyJg and https://bit.ly/34gkxaa The Lancet Rheumatology, online March 26, 2020.
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