Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study

Objective. To evaluate the long-term efficacy and safety of ustekinumab through 2 years in patients with active systemic lupus erythematosus (SLE). Methods. This was a placebo-controlled (week 24), phase II study in 102 patients with seropositive active SLE. Patients were randomized to ustekinumab (approximately 6 mg/kg single intravenous infusion, then subcutaneous [SC] injections of 90 mg every 8 weeks) or placebo, added to background therapy. Placebo patients initiated ustekinumab (90 mg SC every 8 weeks) at week 24. Patients could enter an optional open-label study extension after week 40 (final ustekinumab administration at week 104). Efficacy assessments included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), SLEDAI-2K Responder Index-4 (SRI-4), physician global assessment (PGA), and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Observed data are reported for the extension period. The final efficacy assessment was at week 112; safety was monitored through week 120. Results. In this subset of patients who entered the study extension, 24 in the ustekinumab group and 14 in the placebo crossover group completed study treatment. At week 112, 79% and 92%, respectively, had an SRI-4 response; 92% in both groups had ≥ 4-point improvement from baseline in SLEDAI-2K score; 79% and 93%, respectively, had ≥ 30% improvement from baseline in PGA; 86% and 91%, respectively, had ≥ 50% improvement in active joint (pain and inflammation) count; and 79% and 100%, respectively, had ≥ 50% improvement in CLASI Activity Score. No deaths, malignancies, opportunistic infections, or tuberculosis cases occurred. Safety events were consistent with the known ustekinumab safety profile. Conclusion. Of the 46 patients who entered the voluntary extension of this phase II study, clinical benefit in global and organ-specific SLE activity measures was observed with ustekinumab through 2 years with no new or unexpected safety findings.