Refractory Anti-HMGCR Necrotizing Myopathy With Progressive Hypercapnic Respiratory Failure Responsive to a JAK Inhibitor

Immune-mediated necrotizing myopathy (IMNM) associated with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies is a rare condition often associated with statin use. It typically presents with proximal weakness and markedly elevated creatine phosphokinase (CPK) levels and is often refractory, requiring long-term immunotherapy. Respiratory involvement is uncommon but can be life-threatening. Herein, we report the case of a 73-year-old woman with long-standing anti-HMGCR antibody-positive IMNM, refractory to glucocorticoids, methotrexate, azathioprine, intravenous immunoglobulin (IVIg), rituximab, and plasma exchange (PLEX), who presented with progressive hypercapnic respiratory failure. Despite ongoing treatment with IVIg, PLEX, and high-dose glucocorticoids, the patient's respiratory function worsened, and she required mechanical ventilation (MV). The addition of tofacitinib, a Janus kinase (JAK) inhibitor, coincided with marked clinical improvement, discontinuation of MV, and successful transition to room air. The patient continued to do well on this therapy, with improvement in muscle strength until outpatient discharge. The clinical benefit of JAK inhibition has been reported in dermatomyositis, overlap myositis, and anti-MDA5-positive disease, particularly in refractory cases with pulmonary or systemic involvement-but has not been described in the setting of refractory IMNM. In our patient, who had exhausted multiple conventional therapies and PLEX, the rapid clinical improvement after JAK inhibition strongly suggests a therapeutic effect and highlights the need for future studies of JAK inhibitors in IMNM.