Use of ustekinumab in addition to standard-of-care treatment in patients with active seropositive systemic lupus erythematosus (SLE) has demonstrated improved efficacy and a safety profile consistent with ustekinumab therapy in other diseases, according to the results of a multicenter, double-blind, phase 2, randomized controlled trial (ClinicalTrials.gov identifier: NCT02349061) published in the Lancet.
The investigators sought to evaluate the safety and efficacy of the interleukin 12 and interleukin 23 inhibitor ustekinumab for the treatment of patients with SLE and moderate to severe disease activity despite the use of conventional therapy. Eligible patients were aged 18 to 75 years, weighed ≥35 kg, and had had a diagnosis of SLE for ≥3 months before initial administration of ustekinumab.
Participants were randomly assigned in a 3:2 ratio to the ustekinumab or placebo group, using an interactive web response system, with stratification based on the following factors: skin biopsy, presence of lupus nephritis, baseline SLE medications and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, site, region, and race.
In addition to standard-of-care therapy, patients received an intravenous infusion of ustekinumab, dosed according to weight, followed by subcutaneous injections of ustekinumab 90 mg every 8 weeks, or intravenous infusion of placebo at baseline followed by subcutaneous injections of placebo every 8 weeks. The primary study end point was the proportion of patients who achieved an SLEDAI-2K responder index-4 response at 24 weeks.
A total of 166 patients were screened between October 6, 2015 and November 30, 2016. Researchers randomly assigned 102 of these patients to receive ustekinumab (n=60) or placebo (n=42). At 24 weeks, 62% of participants in the ustekinumab group and 33% of those in the placebo group attained a SLEDAI-2K responder index-4 response (percentage difference, 28%; 95% CI, 10%-47%; P =.006).
Between baseline and 24 weeks, 78% of ustekinumab-treated patients and 67% of placebo-treated patients experienced ≥1 adverse event. Infections were the most commonly reported adverse event (27 in the ustekinumab group vs 21 in the placebo group). There were no deaths or treatment-emergent opportunistic infections, herpes zoster, tuberculosis, or malignancies reported between baseline and 24 weeks.
The investigators concluded that the addition of ustekinumab to standard-of-care treatment was associated with improved clinical and laboratory parameters compared with placebo in the treatment of patients with active SLE, and exhibited a safety profile that was consistent with the use of ustekinumab treatment for other diseases. Larger randomized, placebo-controlled, phase 3 trials are warranted to confirm these findings.
van Vollenhoven RF, Hahn BH, Tsokos GC, et al. Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study [published online September 21, 2018]. Lancet. doi: 10.1016/S0140-6736(18)32167-6