Current Treatment Options for Cutaneous Lupus Erythematosus Are 'Notably Inadequate,' Review Says

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Cutaneous lupus erythematosus (CLE) remains a challenging aspect of systemic lupus erythematosus (SLE) management. Recent developments have unveiled promising therapeutic options, including IFN-targeting therapies, Janus kinase/signal transducers and activators of transcription (JAK/STAT) inhibitors, pDC-directed therapies, B-cell therapies, T-cell therapies, and cereblon-targeting ligands.

While treatments for SLE and CLE may overlap, in that some treatments approved for SLE can be used in cases of CLE, the US Food and Drug Administration has not approved a new systemic treatment for CLE in more than 60 years.¹

In a recent review published in The Journal of Dermatology, researchers Xie et al delved into the current treatment and research landscape of CLE. They concluded that the current options for patients are "notably inadequate."²

IFN-Targeting Therapies

Anifrolumab, an IFN-directed therapy, has showcased significant potential, the review found.

Phase 2 and 3 trials have demonstrated efficacy in reducing disease activity and corticosteroid usage in patients with SLE. Additionally, case studies suggest effectiveness in refractory CLE, emphasizing the need for further investigation to optimize dosing and characterize long-term effects.

JAK/STAT Inhibitors

Deucravacitinib, a selective TYK2 inhibitor, has also exhibited promise in CLE treatment.

Phase 2 trials have revealed superior efficacy in reducing CLASI scores compared to placebo, warranting further exploration in ongoing phase 3 trials.

pDC-Directed Therapies

Litifilimab, a pDC-targeting therapy, has demonstrated encouraging results in both SLE and CLE.

While phase 2 trials exhibited efficacy in reducing disease activity, ongoing studies like LILAC and AMETHYST aim to validate its potential in systemic and cutaneous disease.

B-Cell Therapies

Belimumab, a BAFF receptor antagonist, has emerged as a promising therapy for treatment-resistant CLE.

Pooled analysis from phase 3 trials has revealed substantial improvement in mucocutaneous domains, highlighting its efficacy in managing CLE manifestations.

T-Cell Therapies

Dapirolizumab, an anti-CD40L antibody fragment, has exhibited notable efficacy in reducing Cutaneous LE Disease Area and Severity Index (CLASI) scores in patients with SLE.

Despite not meeting the primary endpoint, ongoing phase 3 trials aim to explore its role in CLE management.

Cereblon-Targeting Ligands

Iberdomide, a cereblon ligand, has demonstrated efficacy in reducing SLE disease activity.

Phase 2 trials have revealed promising results in improving CLASI scores, particularly in cases of SCLE.

Concluding Thoughts

"The current treatment options for CLE are notably inadequate, often necessitating treatment escalation without sufficient control of disease activity. This gap in management significantly impacts quality of life for CLE patients, underscoring a critical need for more optimal treatments," according to review authors Xie et al. "Our existing therapeutic armamentarium consists primarily of broad-spectrum immunosuppressive agents that carry a significant risk of systemic side effects. A crucial ongoing objective is establishment of clinical trials dedicated to CLE for properly tailored inclusion criteria and endpoints focused on cutaneous parameters."

References

1. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Accessed March 21, 2024. Ann Rheum Dis. 2019; 78: 736–745.
2. Xie L, Lopes Almeida Gomes L, Stone CJ, Faden DF, Werth VP. An update on clinical trials for cutaneous lupus erythematosus. J Dermatol. March 15, 2024. Accessed March 21, 2024. doi:10.1111/1346-8138.17161