OP0041 MAINTENANCE OF EFFICACY AND SAFETY AND REDUCTION OF BILAG FLARES WITH USTEKINUMAB, AN INTERLEUKIN-12/23 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): 1-YEAR RESULTS OF A PHASE 2, RANDOMIZED PLACEBO-CONTROLLED, CROSSOVER STUDY

Background Both IL-12 and IL-23 have been implicated in the pathogenesis of SLE. We have previously reported that treatment with an anti-IL-12/23 p40 monoclonal antibody ustekinumab (UST) resulted in greater improvement in several SLE disease measures through week 24 compared with placebo (PBO).1 Objectives Results of global and organ-specific disease measures and flares through 1 year are reported here. Methods We conducted a PBO-controlled phase 2 study in 102 patients with seropositive active SLE (defined by SLICC criteria, SLEDAI score ≥6, and ≥1 BILAG A and/or ≥2 BILAG B scores). Patients were randomized (3:2) to UST (6 mg/kg single IV infusion, then 90 mg SC q8w beginning at week 8, n=60) or PBO (n=42), both added to standard background therapy. Patients receiving PBO crossed over to UST (90 mg SC q8w) at week 24. The primary endpoint was the proportion of patients achieving SLE Responder Index (SRI)-4 response at week 24. Modified intention-to-treat (mITT) analyses across SLE disease measures were performed to evaluate maintenance of response with UST between week 24 and week 48 and severe BILAG flares (≥1 new BILAG A score). Safety was assessed through week 56. Results As previously reported, SRI-4 response rate at week 24 was significantly greater (p=0.0057) in patients receiving UST (62%) vs PBO (33%).1 In the UST group, SRI-4 (week 24: 62% vs week 48: 63%), SRI-5 (week 24: 43% vs week 48: 48%), and SRI-6 (week 24: 43% vs week 48: 47%) response rates were sustained at 1 year. Proportions of patients with ≥4-point improvement from baseline in SLEDAI-2K score (week 24: 65% vs week 48: 67%) and with ≥30% improvement from baseline in Physician’s Global Assessment score (week 24: 68% vs week 48: 75%) were also maintained in the UST group. UST response rates were also sustained through 1 year in organ-specific disease measures (≥50% improvement in active joint counts: week 24: 87% vs week 48: 87%; ≥50% improvement in CLASI activity score: week 24: 53% vs week 48: 69%). In PBO patients who crossed over to UST at week 24 (n=33), response rates across outcomes studied were 10-20% higher at week 48 vs week 24. Flare rates for patients with severe BILAG flares were 2.1/10,000 patient-days in week 0-24 and 1.1/10,000 patient-days in week 24-48 in the UST group. In the PBO group, severe BILAG flare rates were 8.4/10,000 patient-days in week 0-24 and, following UST crossover, were 4.6/10,000 patient-days in week 24-48. The occurrence of severe BILAG flares seemed to diminish after approximately 8 weeks (week 8 in UST arm, week 32 in PBO arm) of treatment with UST (Figure). No deaths, malignancies, opportunistic infections, tuberculosis cases, or unexpected serious AEs (SAEs) were observed. Incidences of ≥1 SAE were UST (week 0-24) 8.3%, PBO (week 0-24) 9.5%, UST (week 24-48) 8.9%, and PBO-UST (week 24-48) 12.1%. Safety events were consistent with the known UST safety profile. Conclusion UST provided sustained clinical benefit in global and organ-specific SLE-activity measures and reduced flares through 1 year, with a safety profile consistent with other indications. Thus, UST may have durable therapeutic benefit in SLE. Reference [1] van Vollenhoven RF, et al. Lancet2018;392:1330. Disclosure of Interests Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB, Consultant for: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex., George Tsokos Grant/research support from: Janssen Research & Development, LLC, Robert Gordon Employee of: Janssen Research & Development, LLC, Kim Hung Lo Employee of: Janssen Research & Development, LLC, Y Irene Gregan Employee of: Janssen Research & Development, LLC, Kaiyin Fei Employee of: Janssen Research & Development, LLC, Shawn Rose Employee of: Janssen Research & Development, LLC, Bevra H. Hahn Grant/research support from: Janssen Research & Development, LLC