Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus

Ronald F van Vollenhoven; Kenneth C Kalunian; Thomas Dörner; Bevra H Hahn; Yoshiya Tanaka; Robert M Gordon; Cathye Shu; Kaiyin Fei; Sheng Gao; Loqmane Seridi; Patrick Gallagher; Kim Hung Lo; Pamela Berry; Qing C Zuraw

doi:10.1136/ard-2022-222858

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus

Ann Rheum Dis. 2022 Jul 7;81(11):1556-1563. doi: 10.1136/ard-2022-222858. Online ahead of print.

Authors

Ronald F van Vollenhoven¹, Kenneth C Kalunian², Thomas Dörner³, Bevra H Hahn⁴, Yoshiya Tanaka⁵, Robert M Gordon⁶, Cathye Shu⁷, Kaiyin Fei⁷, Sheng Gao⁸, Loqmane Seridi⁸, Patrick Gallagher⁹, Kim Hung Lo⁶, Pamela Berry¹⁰, Qing C Zuraw⁷

Affiliations

¹ Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands r.vanvollenhoven@amsterdamumc.nl.
² Division of Rheumatology, Allergy and Immunology, University of California San Diego, La Jolla, California, USA.
³ Department of Med./Rheumatology and Clinical Immunology, Charite Univ. Hospital, Berlin, Germany.
⁴ Rheumatology, UCLA School of Medicine, Los Angeles, California, USA.
⁵ First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁶ Statistics and Decision Sciences, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
⁷ Clinical Development Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
⁸ Translational Sciences and Medicine, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
⁹ Portfolio Delivery Operations, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
¹⁰ Immunology Strategic Market Access, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, Pennsylvania, USA.

Abstract

Objective: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care.

Methods: Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24.

Results: At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event.

Conclusions: Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab.

Trial registration number: NCT03517722.

Keywords: autoimmune diseases; biological therapy; lupus erythematosus, systemic.

Associated data

ClinicalTrials.gov/NCT03517722