Cladribine use for multiple sclerosis with autoimmune comorbidities: retrospective analysis of the French MS registry, case series, and therapeutic considerations

Background: Autoimmune (AI) comorbidities are common in people with multiple sclerosis (MS) and may complicate therapeutic management, particularly when dual immunosuppression is required. Cladribine, an immune reconstitution therapy approved for relapsing MS, has shown potential benefit in selected autoimmune disorders. Objectives: To evaluate the prevalence of AI comorbidities in a large French MS cohort and explore the potential efficacy of cladribine in MS patients with concomitant autoimmune diseases. Design: Retrospective multicenter registry analysis combined with a descriptive case series and literature review. Data sources and methods: Data were retrospectively extracted from the European Database for MS across five French tertiary MS centers. Adults with MS and documented autoimmune comorbidities were identified, including a subgroup treated with oral cladribine. In addition, eight detailed clinical cases of MS associated with autoimmune diseases treated with cladribine were reviewed to assess outcomes on both MS and the associated autoimmune condition. Results: Among 11,410 people with MS, 901 had at least one autoimmune comorbidity, corresponding to a prevalence of 7.9 ± 0.25% (age 50.8 years), with a predominance of women. Of 385 cladribine-treated patients, 39 (10.1% ± 1.54%) had concurrent autoimmune disorders, although this proportion did not significantly differ from the overall cohort ( p = 0.11). Eight cases involving ankylosing spondylitis ( n = 3), psoriatic arthritis ( n = 2), psoriasis ( n = 1), rheumatoid arthritis ( n = 1), and sarcoidosis ( n = 1) were analyzed. Cladribine was consistently associated with MS stability, while efficacy on associated autoimmune conditions was variable, with more favorable outcomes observed in ankylosing spondylitis, psoriasis, and sarcoidosis. Conclusion: Autoimmune comorbidities affect approximately 8% of the French MS population and are more frequent in women. Cladribine may represent a useful therapeutic option in selected patients with concomitant autoimmune disorders, potentially limiting prolonged dual immunosuppression. Larger prospective studies are required to confirm efficacy and safety. Trial registration: OFSEP/EDMUS registry, ClinicalTrials.gov: NCT02889965.