Ustekinumab shows potential for SLE
medwireNews: Add-on treatment with the interleukin (IL)-12 and -23 inhibitor ustekinumab may be beneficial for patients with systemic lupus erythematosus (SLE), phase II study results suggest.
“[O]nly a single drug with a novel mechanism of action has been approved for systemic lupus erythematosus in almost six decades”, and therefore “a significant unmet need remains for these patients”, the study authors write in The Lancet.
Ronald van Vollenhoven (Amsterdam Rheumatology and Immunology Center, the Netherlands) and co-investigators randomly assigned 102 patients with moderate-to-severe autoantibody-positive SLE despite conventional treatment to receive intravenous ustekinumab at a dose of 90 mg every 8 weeks following a loading dose of 260–520 mg (dependent on bodyweight), or to receive placebo. All patients continued to receive standard treatment throughout the trial, including glucocorticoids (81–85%) and antimalarial agents (62–73%).
At the 24-week follow-up, 62% of 60 patients in the ustekinumab arm achieved an SLE responder index (SRI)-4 response, compared with just 33% of 42 participants given placebo, a significant difference.
Patients in the ustekinumab group also had a significantly greater mean improvement in SLEDAI-2K score and were significantly less likely to experience flares over the follow-up period.
The researchers note, however, that a comparable proportion of patients in the ustekinumab and placebo groups achieved a BILAG-based combined lupus assessment (BICLA) response at week 24, at 35% and 33%, respectively.
“Although the SRI-4 and BICLA responses were inconsistent in this study, the totality of the efficacy findings suggests that ustekinumab might benefit both global and organ-specific disease activity in systemic lupus erythematosus”, write van Vollenhoven and team.
“Safety results were consistent with the known safety profile of ustekinumab”, they add. In all, 78% of patients given ustekinumab and 67% of those in the placebo group experienced adverse events, most commonly infections, and a corresponding 8% and 10% experienced serious adverse events.
The authors of an accompanying commentary, Nathalie Costedoat-Chalumeau (Cochin Hospital, Paris, France) and Frédéric Houssiau (Cliniques Universitaires Saint-Luc, Brussels, Belgium), describe the phase II findings as “notable”, highlighting the large difference in SRI-4 response rates between the groups and the “good safety profile” of ustekinumab.
Nonetheless, they point out that the trial was limited by the small number of participants and the exclusion of patients with renal involvement.
The investigators conclude that their findings “confirm the importance of IL-12 and IL-23 in this disease”, and note that ustekinumab is now undergoing further testing in a phase III trial of SLE patients.
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