Purpose IL12 and IL23 pathway have been linked to SLE pathogenesis. Anti-IL12/23 monoclonal antibody ustekinumab (UST) previously approved for psoriasis, psoriatic arthritis, and Crohn’s diseasewas evaluated in pts with active SLE.

Methods A Ph2, PBO-controlled study in 102 adults with seropositive SLE by SLICC criteria with active disease despite standard-of-care therapy were randomised to UST vs PBO, added to standard care. Primary endpoint was the proportion achieving SLE response index (SRI)−4 response at wk24. Secondary endpoints included change SLEDAI-2K, Physician’s Global Assessment (PGA), and BICLA response.

Results The mITT population (includes pts who received at least one dose) at wk24 revealed 60% of UST pts with SRI-4 response vs 31% in PBO (p=0.0046). Pts in UST group had greater median change from wk0 to wk24 in SLEDAI-2K and PGA vs PBO (table 1). No difference was observed in BICLA composite response at wk24, but more UST pts had no BILAG worsening vs PBO. Through wk24, 78% of UST pts and 67% of PBO pts had greater than or equal to 1 AE; 8.3%–9.5%, respectively, had greater than or equal to 1 SAE (table 1). There were no deaths in the study. Safety events were consistent with UST safety profile in other studied indications.

Conclusion UST showed efficacy in treatment of active SLE vs PBO and comparable safety warranting further investigation. UST may work via a novel mechanism of action in SLE.