Janus kinase and calcineurin-inhibitor combination in anti-MDA5 dermatomyositis: No significant survival benefit but reassuring safety profile.

OBJECTIVES: Anti-MDA5 dermatomyositis (anti-MDA5 DM) is the most severe subtype of dermatomyositis, due to its pulmonary involvement. Current treatment involves corticosteroids and immunosuppressants, but variability in responses exists. This study aims to evaluate the efficacy and safety of Janus kinase (JAK)- and calcineurin-inhibitor combination (JAK-CNI) in anti-MDA5 DM patients. METHODS: A nested case-control study was conducted within a retrospective cohort of 234 anti-MDA5 DM patients. Patients receiving JAK-CNI were matched 1:2 with comparators. All-cause mortality or transplant within a year was compared using Cox proportional hazards models. Infectious and noninfectious side effects were also assessed. RESULTS: Twenty-seven patients receiving JAK-CNI were compared to 52 matched controls. Almost all these patients had pulmonary involvement. Thirty-nine (49%) died or were transplanted during follow-up. No significant improvement in survival or transplant-free survival was observed with JAK-CNI compared with comparators (hazard ratios 1.02, 95% confidence intervals [0.48-2.16]). Results were consistent regardless of intensive care unit (ICU) admission status and when analyses were restricted to patients with rapidly progressive interstitial lung disease. A trend toward a beneficial effect of the JAK-CNI combination was observed in non-ICU patients. Infectious complications were frequent (n = 49, 62%), with no excess risk in patients receiving JAK-CNI. CONCLUSION: JAK-CNI showed a similar outcome to other immunosuppressive combinations. However, as the study included the most severe cases, the potential benefit of early JAK-CNI introduction in less severe forms cannot be dismissed, as suggested by the nonsignificant trend in non-ICU patients. Future studies are needed to clarify the optimal timing and patient selection for JAK-CNI therapy in anti-MDA5 DM.