Safety was as expected based on earlier extensive experience with the agent in psoriasis, psoriatic arthritis (PsA), and Crohn’s disease (CD). Based on these results, ustekinumab – with a novel mechanism of action – may have the potential to offer a new treatment option for patients with SLE.
A Dutch study by Van Vollenhoven et al. evaluated ustekinumab, a monoclonal antibody that blocks the shared p40 subunit of the cytokines interleukin (IL)12 and IL23 in patients with active SLE. A Phase 2, placebo-controlled study was conducted in 102 patients with active SLE. They were randomized (3:2) to receive ustekinumab 6 mg/kg or placebo at week 0, followed by ustekinumab 90 mg or placebo subcutaneous injections every 8 weeks beginning at week 8, and both added to standard care. The primary endpoint was the proportion of patients achieving SLE responder index (SRI)-4 response at week 24.
Secondary endpoints were changed from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), Physician Global Assessment (PGA), and the British Isles Lupus Assessment Group (BILAG)-based Composed Lupus Assessment (BICLA) response. Additional pre-specified endpoint analyses included no BILAG worsening, which was defined as no new BILAG A and ≤1 new BILAG B domain, and BILAG flare (≥1 new BILAG A or ≥2 new BILAG B domain score).
The results show that ustekinumab exhibits a statistically significant improvement in SRI-4 response at week 24 compared to placebo (60% vs 31%, P=0.0046). Patients on ustekinumab had greater median change from baseline SLEDAI-2K and PGA vs placebo (-4.4 vs -3.8 and -2.17 vs -1.93, respectively). No difference was observed in the BICLA response at week 24. However, in the ustekinumab group vs placebo, more patients had no BILAG worsening (48.3% vs 26.25, P=0.028) and the risk of a new BILAG flare was significantly lower (hazard ratio 0.11 [95% CI 0.01-0.94]; P=0.0078). Moreover, ustekinumab demonstrates improvement in musculoskeletal and mucocutaneous disease features vs placebo, with the mean change from baseline in the active joint count at week 24 of -4.5 for ustekinumab and -2.8 for placebo (median value -4.0 and -3.0, respectively).
Low C3 and elevated anti-double-stranded DNA (dsDNA) autoantibody levels, which are markers of increased disease activity, improved in ustekinumab patients over time when compared to placebo. C-levels and antinuclear antibody (ANA) titers were stable over time in both treatment groups. With regard to adverse events (AEs), through week 24, 78% of patients on ustekinumab vs 67% of placebo patients had ≥1AE; 8.3% & 9.5%, respectively, and had ≥1 serious AE. No deaths occurred during the study and it was concluded that the overall safety profile was comparable between ustekinumab and placebo (1).
Van Vollenhoven R, et al. Efficacy and safety of ustekinumab in patients with active systemic lupus erythematosus: Results of phase 2, randomized placebo-controlled study. Abstract FRI0303. EULAR 2018.