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).
Sources:
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.