Efficacy and safety of emerging immunomodulatory agents versus standard therapies in refractory cutaneous lupus: A systematic review
DOI:
https://doi.org/10.25251/52gar039Keywords:
anifrolumab, belimumab, immunomodulation, lupus erythematosus, cutaneous, refractory diseaseAbstract
Background: Refractory cutaneous lupus (RCL) remains challenging to treat, with limited response to standard therapies. Emerging immunomodulatory agents, including thalidomide, lenalidomide, anifrolumab, belimumab, and intravenous immunoglobulin, may offer improved outcomes.
Methods: A systematic review was conducted following PRISMA guidelines. Randomized controlled trials evaluating the efficacy and safety of the specified agents in adults with RCL were included. Databases searched included MEDLINE, Embase, and LILACS. Primary outcomes were CLASI, BICLA, and SRI‑4 response rates. Secondary outcomes included adverse events and quality of life.
Results: Anifrolumab achieved CLASI‑50 in up to 63.0% of patients versus 30.8% with placebo and BICLA response in up to 53.5% versus 25.7%. Belimumab improved SRI‑4 response to 43.2% versus 33.5% with placebo. RSLV‑132 and tofacitinib demonstrated partial efficacy. Herpes zoster was more frequent with anifrolumab.
Conclusion: Anifrolumab and belimumab provide superior efficacy with acceptable safety in RCL, supporting their inclusion in personalized treatment algorithms.
References
1. Alsukait S, Learned C, Rosmarin D. Open-label phase 2 pilot study of oral tofacitinib in adult subjects with discoid lupus erythematosus (DLE). J Drugs Dermatol. 2023;22:425-427. [PMID: 37026882].
2. Barikbin B, Givrad S, Yousefi M, et al. Pimecrolimus 1% cream versus betamethasone 17-valerate 0.1% cream in the treatment of facial discoid lupus erythematosus: a double-blind, randomized pilot study. Clin Exp Dermatol. 2009;34:776-780. [PMID: 19456797].
3. Burge DJ, Werth VP, Boackle SA, et al. Evaluation of RNase therapy in systemic lupus erythematosus: a randomized phase 2a clinical trial of RSLV 132. Lupus Sci Med. 2024;11:e001113.
4. Carter L, Wigston Z, Laws P, et al. An emerging role of interferon targeted therapy in mucocutaneous SLE: a prospective real world evaluation of anifrolumab for refractory cutaneous lupus. Rheumatology (Oxford). 2023;62(Suppl_1).
5. Carter L, Wigston Z, Laws P, et al. An emerging role of interferon targeted therapy for the treatment of cutaneous systemic lupus erythematosus: a prospective real world evaluation of anifrolumab for refractory cutaneous lupus. Br J Dermatol. 2023;188(Suppl_1).
6. Centner CS, Robertson NM, Kang J, et al. Treatment of discoid lupus with lenalidomide and anifrolumab: case report and review of the literature. Lupus. 2024;33:1487 1491.
7. Flouda S, Emmanouilidou E, Karamanakos A, et al. Efficacy of anifrolumab in multi refractory skin manifestations of systemic lupus erythematosus: case series. Lupus Sci Med. 2024;11(Suppl_1):A112.2.
8. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti–interferon α receptor monoclonal antibody, in moderate to severe systemic lupus erythematosus. Arthritis Rheumatol. 2017;69:376 386.
9. Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP 1): a randomized, controlled, phase 3 trial. Lancet Rheumatol. 2019;1:e208 e219.
10. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo controlled study of belimumab in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918 3930.
11. Plüß M, Piantoni S, Wincup C, et al. Rapid response of refractory systemic lupus erythematosus skin manifestations to anifrolumab—a case based review of clinical trial data suggesting a domain based therapeutic approach. J Clin Med. 2022;11:3449.
12. Tzung TY, Liu YS, Chang HW. Tacrolimus vs clobetasol propionate in the treatment of facial cutaneous lupus erythematosus: a randomized, double blind, bilateral comparison study. Br J Dermatol. 2007;156:191 192.
13. Wang X, Zhang L, Luo J, et al. Tacrolimus 0.03% ointment in labial discoid lupus erythematosus: a randomized, controlled clinical trial. J Clin Pharmacol. 2015;55:1221 1228.
14. Khan MA, Khan FH, Khan HB, et al. Role of anifrolumab in refractory cutaneous manifestations of lupus erythematosus: a case series and literature review [Internet]. Cureus. 2023 May 27 [cited 2025 Jul 27].
Downloads
Published
Data Availability Statement
The data supporting the findings of this study are available within the article and its supplementary materials. No additional datasets were generated or analyzed during the current study.
Issue
Section
License
Copyright (c) 2026 Francisco Javier Gómez Ballesta, Mariel Cecilia Paternina Álvarez, Ana Isabel Betancourt Benítez, María José Montiel Salas, Sergio Armando López Bermúdez, Juan Pablo Alzate Granado (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
