Ronald van Vollenhoven
CHICAGO — The anti-IL 12/23 p40 monoclonal antibody ustekinumab was associated with improved global and organ-specific systemic lupus erythematosus activity measures that were sustained through 1 year, with a safety profile consistent with the drug’s other indications.
“Systemic lupus erythematosus is a very complex pathophysiology that is only partially understood. It has been analyzed in great detail and in many different ways, and it is clear that IL-12 may play a role ... and IL-23 ... may also play a role in the immunopathologic processes in this disease,” Ronald van Vollenhoven, MD, PhD, of the Amsterdam Rheumatology and Immunology Center ARC, said during the plenary 3 session. “The fact that an antagonist of IL-12 and 23 is already available for the treatment of other rheumatic diseases — psoriatic arthritis, as well as for psoriasis — was of interest.”
van Vollenhoven and colleagues conducted a phase 2, randomized, placebo-controlled crossover study of 102 patients with seropositive SLE, defined as SLEDAI score 6 or higher, and BILAG A score of 1 or higher and/or BILAG B score of 2 or higher. In addition to standard care, patients were assigned 3:2 to 6 mg/kg single IV loading dose of ustekinumab (Stelara, Janssen), then 90 mg subcutaneous ustekinumab every 8 weeks starting at week 8, or placebo. Crossover from placebo to 90 mg subcutaneous ustekinumab every 8 weeks occurred at week 24.
The primary endpoint was number of patients who achieved SLE response index (SRI)-4 at 24 weeks. Maintenance of response with ustekinumab from week 24 to week 48 was assessed using modified intention-to-treat analyses across disease activity measures. Safety assessment occurred through week 56.
Baseline: 91% female, 41 years, disease duration 9.6 years; groups were well balanced.
According to data from the primary endpoint analysis, SRI-4 response rate was significantly higher in the ustekinumab group compared with placebo at 24 weeks (61.7% vs. 33.3%; P = .0057) and sustained through 1 year (63.3%). In the ustekinumab group, measures of disease activity were also sustained from week 24 to 1 year, including SLEDAI-2K (65% at 24 weeks and 66.7% at 1 year), Physician Global Assessment (PGA; 67.9% at 24 weeks and 75% at 1 year) and active joint responses (86.5% at 24 weeks and 1 year). By week 28, CLASI response rate in the ustekinumab group plateaued (53.1% at 24 weeks and 67.7% at 28 weeks) but was maintained through 1 year (68.6%).
More than half (54.5%) of patients who crossed over from placebo to ustekinumab at week 24 (n = 33) achieved an SRI-4 response at 1 year, according to van Vollenhoven.
One or more treatment-related adverse events occurred among 81.7% of patients assigned to ustekinumab; 15.1% of patients experienced one or more serious adverse events and 7.5% had one or more serious infections through 1 year. Van Vollenhoven and colleagues reported no instances of death, malignancy, opportunistic infection or tuberculosis.
“It’s fair to say ustekinumab may be an effective and well-tolerated therapy for systemic lupus erythematosus and warrants further evaluation in a phase 3 randomized, placebo-controlled trial — a trial that has now already been initiated,” he said. – by Stacey L. Adams
Disclosure: van Vollenhoven reports a relationship with Janssen Research & Development, LLC. Please see the study for all other authors’ relevant financial disclosures.
van Vollenhoven R. Abstract 2785. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.