Cesaroni M, Seridi L, Loza MJ, et al. - This study was carried out to ascertain if modulation of the expression of IL‐12, IL‐23, or both cytokines by ustekinumab is associated with clinical efficacy in patients with systemic lupus erythematosus (SLE). Researchers designed a phase II randomized, placebo‐controlled study including a total of 102 patients with autoantibody‐positive SLE whose disease remained active despite standard‐of‐care therapy. Individuals were assigned randomly in a 3:2 ratio to receive ~6 mg/kg ustekinumab intravenously or placebo at week 0, followed by subcutaneous injections of 90 mg ustekinumab or placebo every 8 weeks, with placebo crossover to 90 mg ustekinumab every 8 weeks. The results exhibited that, while not diminishing the potential role of IL‐23, these serum biomarker assessments demonstrate that IL‐12 blockade has an important role in the mechanism of action of ustekinumab treatment in patients with SLE.