medwireNews: Development of ustekinumab as a potential therapeutic option for systemic lupus erythematosus (SLE) has been terminated following an interim analysis of the phase 3 LOTUS trial, which demonstrated no benefit of the interleukin (IL)-12/23 inhibitor in this patient population.
These findings contrast with those from an earlier phase 2 study, in which participants treated with ustekinumab had significantly greater SRI-4 response rates at week 24 compared with those given placebo.
The preplanned interim analysis of the current study, published in the Annals of the Rheumatic Diseases, included 289 patients (approximately 95% women) with active SLE despite treatment with glucocorticoids, antimalarials, and/or immunomodulatory drugs.
These people were randomly assigned to receive add-on treatment with subcutaneous injections of ustekinumab 90 mg every 8 weeks (following an intravenous loading dose of approximately 6 mg/kg at week 0) or placebo for 48 weeks. Approximately 80% of participants were receiving glucocorticoids at baseline, and around three-quarters were taking antimalarials.
The primary endpoint of the study was not met, with numerically lower SRI-4 response rates at 1 year among the 173 participants in the ustekinumab group than the 116 in the placebo arm, at 43.9% and 56.0%, respectively.
“The high response rate seen in the placebo/standard-of-care group in LOTUS, with nearly 60% of these patients achieving an SRI-4 response at week 52, may have blunted the ability to assess the efficacy of ustekinumab,” suggest Ronald van Vollenhoven (Amsterdam Rheumatology and Immunology Center, the Netherlands) and co-investigators. They note that SRI-4 response rates in the placebo groups of other recent SLE trials “were lower than that observed in LOTUS.”
The investigators say that “there were no appreciable differences” between the two treatment groups in terms of major secondary endpoints either, including BILAG flare rates and improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index scores between baseline and 1 year, and SRI-4 response rates at week 24. Among patients receiving glucocorticoids at baseline, a higher proportion of those treated with ustekinumab versus placebo achieved a decrease in glucocorticoid dose at week 40 that was maintained at 1 year (44 vs 29%).
Despite this “numerical trend suggesting that steroid tapering was possible to a greater extent in the ustekinumab group compared with the placebo group, there was insufficient evidence to support continuation of development of ustekinumab in patients with SLE,” and the sponsor terminated the study, say van Vollenhoven et al.
They note that no new safety signals were observed in the LOTUS trial, and adverse events were “consistent with the known safety profile of ustekinumab.”
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