van Vollenhoven RF, et al. - In patients with moderate-to-severe disease despite conventional treatment, researchers tested the safety and effectiveness of ustekinumab for the treatment of systemic lupus erythematosus. In the treatment of active systemic lupus erythematosus, the addition of ustekinumab to standard-of-care treatment brought about better effectiveness in clinical and laboratory parameters vs placebo. The safety profile was consistent with ustekinumab therapy in other diseases. The most common type of adverse event was infections. In this analysis, further development of ustekinumab as a novel treatment in systemic lupus erythematosus was supported.

Methods

• It was a multicenter, double-blind, phase 2, randomized, controlled trial.
• Participants were adult patients with active, seropositive systemic lupus erythematosus, at 44 private practices and academic centers in Argentina, Australia, Germany, Hungary, Mexico, Poland, Spain, Taiwan, and US.
• Eligibility criteria included being 18–75 years of age, weighing at least 35 kg, and having a diagnosis of systemic lupus erythematosus at least 3 months before the first administration of study drug.
• For this investigation, eligible subjects were randomly assigned (3:2) to the ustekinumab or placebo group using an interactive web response system with stratification by skin biopsy, lupus nephritis presence, baseline systemic lupus erythematosus medications and systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score combined factor, site, region, and race.
• After that, patients and investigators were masked to treatment allocation.
• Study participants received an intravenous infusion of ustekinumab (260 mg for patients weighing 35–55 kg, 390 mg for patients weighing >55 kg and ≤85 kg, and 520 mg for patients weighing >85 kg) followed by subcutaneous injections of ustekinumab 90 mg every 8 weeks or intravenous infusion of placebo at week 0 followed by subcutaneous injections of placebo every 8 weeks, both in addition to standard-of-care therapy.
• The proportion of patients achieving a SLEDAI-2K responder index-4 (SRI-4) response at week 24 was the primary endpoint.
• Researchers performed efficacy analyses in a modified intention-to-treat population of patients who received at least one dose (partial or complete, intravenous or subcutaneous) of their randomly assigned study treatment.
• Irrespective of group assignment, safety analyses were done in all patients who received at least one dose of study treatment.

Results

• One hundred sixty-six patients were screened, of whom 102 were randomized to receive ustekinumab (n=60) or placebo (n=42) between October 6, 2015 and November 30, 2016.
• It was observed that 37 (62%) of 60 patients in the ustekinumab group and 14 (33%) of 42 patients in the placebo group achieved an SRI-4 response (percentage difference 28% [95% CI 10–47], p=0·006) at week 24.
• It was noted that 47 (78%) of 60 patients in the ustekinumab group and 28 (67%) of 42 patients in the placebo group had at least one adverse event between week 0 and week 24.
• The most common type of adverse event (27 [45%] in the ustekinumab group vs 21 [50%] in the placebo group) was infections.
• Between weeks 0–24, no deaths or treatment-emergent opportunistic infections, herpes zoster, tuberculosis, or malignancies occurred.