Effect of iberdomide on cutaneous manifestations in systemic lupus erythematosus: A randomized phase 2 clinical trial - 22/11/24

Doi : 10.1016/j.jaad.2024.09.074

Victoria P. Werth, MD ^a,^⁎ , Joan T. Merrill, MD ^b, Richard Furie, MD ^c, Thomas Dörner, MD ^d, Ronald van Vollenhoven, MD, PhD ^e, Peter Lipsky, MD ^f, Michael Weiswasser, MPH ^g, Shimon Korish, MD ^g, Peter H. Schafer, PhD ^g, Mark Stern, PhD ^g, Stan Li, MS ^g, Nikolay Delev, MD ^g
^a University of Pennsylvania and the Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania
^b Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma
^c Northwell Health, Great Neck, New York
^d German Rheumatism Research Center and Charité University Hospital, Berlin, Germany
^e Amsterdam University Medical Centers, Amsterdam, The Netherlands
^f RILITE Foundation and AMPEL BioSolutions, Charlottesville, Virginia
^g Bristol Myers Squibb, Princeton, New Jersey

^∗Correspondence to: Victoria P. Werth, MD, Penn Dermatology, Perelman Center for Advanced Medicine, 3400 Civic Center Boulevard, Philadelphia, PA 19104.Penn DermatologyPerelman Center for Advanced Medicine3400 Civic Center BoulevardPhiladelphiaPA19104

En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Friday 22 November 2024

Abstract

Background

Iberdomide, a cereblon modulator, promotes degradation of transcription factors Ikaros and Aiolos.

Objective

Evaluate iberdomide efficacy and safety in cutaneous lupus erythematosus (CLE) in a phase 2 study.

Methods

Patients were randomized (2:2:1:2) to iberdomide 0.45 (n = 81), 0.30 (n = 82), or 0.15 mg (n = 42) or placebo (n = 83) daily while continuing background lupus medications.

Results

The mean (SD) baseline Cutaneous Lupus Area and Severity Index Activity (CLASI-A) score was 6.9 (7.0); 28% of patients had a score ≥8; 56% had acute CLE, 29% chronic CLE, and 16% subacute CLE. Mean CLASI-A improvement in patients with baseline score ≥8 was 39.7% for iberdomide 0.45 mg versus 20.1% for placebo at week 4 (P = .032), with continued improvement through week 24 (66.7% vs 54.2%; P = .295). Proportions of patients achieving ≥50% CLASI-A reduction from baseline at week 24 were significantly greater for iberdomide 0.45 mg versus placebo for patients with subacute (91.7% vs 52.9%, P = .035) and chronic (62.1% vs 27.8%; P = .029) CLE but not for the overall population (55.6% vs 44.6%) or patients with baseline CLASI-A ≥8 (66.7% vs 50.0%).

Limitations

Small patient subgroups of CLE subtypes.

Conclusions

Iberdomide showed beneficial effects when added to background lupus medications in patients with subacute and chronic CLE.

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Key words : Aiolos, cereblon modulator, Cutaneous Lupus Area and Severity Index Activity score, cutaneous lupus erythematosus, Ikaros, systemic lupus erythematosus

Abbreviations used : CI, CLASI-50, CLASI-A, CLE, IFN, SLE, SLEDAI, SRI-4, TEAE

Esquema

Introduction

Methods

Trial design, randomization, and interventions

Patients

Endpoints and assessments

Data sharing statement

Role of the funder/sponsor

	Funding sources: This study received funding from Bristol Myers Squibb.
	Patient consent: Consent for the publication of recognizable patient photographs was obtained by the author and all patients with the understanding that this information may be publicly available.
	IRB approval status: Reviewed and approved by each site.
	Primary data from this study were published: Merrill JT, et al. N Engl J Med. 2022;386:1034-1045.