Phase II results support further investigation of baricitinib for SLE
medwireNews: Phase II trial results published in The Lancet suggest that adding the Janus kinase (JAK) 1 and 2 inhibitor baricitinib to standard care may be beneficial for patients with systemic lupus erythematosus (SLE).
The investigators randomly assigned 314 patients with active SLE involving skin or joints to receive 24 weeks of treatment with baricitinib at a dose of 2 mg or 4 mg, or to receive placebo. The study drug was given alongside usual treatment; 73% of patients were receiving corticosteroids at baseline, whilst 71% were receiving antimalarials and 45% were on immunosuppressants.
At the 24-week follow-up, patients receiving baricitinib 4 mg were significantly more likely than those given placebo to achieve resolution of arthritis or rash as defined by the SLE Disease Activity Index-2000, with rates of 67% versus 53% and an odds ratio of 1.8.
Patients who received baricitinib 2 mg also had higher rates of arthritis or rash resolution than those in the placebo group (58 vs 53%), but the difference did not reach statistical significance.
Similarly, patients treated with baricitinib 4 mg, but not the 2 mg dose, were significantly more likely to achieve a SLE Responder Index-4 response and had significantly greater improvements in Physician’s Global Assessment of Disease Activity scores than patients given placebo.
The safety profile of baricitinib in this trial “was consistent with published findings in patients receiving baricitinib in other studies”, as well as “with other drugs used to treat active [SLE]”, report Daniel Wallace (Cedars-Sinai Medical Center, Los Angeles, California, USA) and co-investigators.
A total of 10% of patients in the baricitinib 2 mg and 4 mg groups, and 5% of those given placebo, experienced serious adverse events. The corresponding rates of serious infection were 2%, 6% and 1%, and one patient in the baricitinib 4 mg group experienced a single episode of deep vein thrombosis.
“This study provides the foundation for future phase 3 trials of JAK1/2 inhibition with baricitinib as a new potential oral therapy for [SLE]”, the team says.
Discussing these findings in an accompanying commentary, Johanna Mucke and Matthias Schneider, both from Heinrich-Heine-University Düsseldorf in Germany, say that “the most important aspect is the dosage of baricitinib”.
Given that baricitinib 2 mg demonstrated “almost no effect”, and the 4 mg dose only had a moderate effect with favourable toxicity, “a higher daily dose might be indicated, especially when patients with higher disease activity are included”, they add.
And the commentators believe that “[b]efore any further trials, a careful assessment of responders and non-responders with respect to their pathophysiological background is mandatory”.
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