Research letter

Long-term efficacy and safety outcomes of lenalidomide for cutaneous lupus erythematosus: A multicenter retrospective observational study of 40 patients

Little is known about the prevalence and factors associated with long-term remission in cutaneous lupus erythematosus (CLE).

To assess the prevalence, the factors associated with remission, and the long-term remission with and without treatment during CLE.

Longitudinal cohort study including biopsy-proven patients with CLE seen between November 1, 2019 and April 30, 2021, with at least 6 months of follow-up after diagnosis. Demographic data, CLE subtypes, remission status, and treatments were recorded. Remission was defined by a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score of 0. Long-term remission was defined by remission >3 years.

Among 141 patients included (81% of women), 93 (66%) were in remission at last follow-up with a median duration since diagnosis of 11.4 years (interquartile range, 4.2-24.7). Long-term remission was observed in 22 (19%) of 114 patients with at least 3 years of follow-up, including 5 (4.4%) with no systemic treatment. Active smoking (odds ratio, 0.22 [95%CI: 0.05-0.97]; P = .04) and discoid CLE lesions (odds ratio, 0.14 [95%CI, 0.04-0.48]; P = .004) were associated with a lower risk of long-term remission.

Partial retrospective data collection and tertiary center population.

Long-term remission is rare in CLE and negatively associated with active smoking and discoid CLE.

VEXAS syndrome has an unmet need for therapeutic interventions. Even if few data exist regarding the treatment of this newly described syndrome, different options can be proposed given the unique pathophysiological consequences of the clonal dominance of UBA1 mutated hematopoietic stem cells. To date, allogeneic transplantation is the only curative option, but many questions remain regarding the selection of eligible patients, the conditioning regimen or management of toxicities that may be unique to VEXAS patients. Alternatively, drugs used in myelodysplastic syndrome such as hypomethylating agents or lenalidomide are interesting candidates, which could theoretically have also an effect on the clone. Another strategy is to target the inflammatory cascade, by inhibiting proinflammatory cytokines (such as TNFα, IL1, IL6) or effector cells, for example with JAK inhibitors. Whatever the choice of treatment for VEXAS patients, supportive care is always needed to be considered to manage frequent complications such as cytopenia, thrombosis and infections. Finally, we discuss the challenges of the design of clinical trials for VEXAS patients, from inclusion criteria to clinical and biological endpoints of activity.