Concurrent immune thrombocytopenia and amyotrophic lateral sclerosis with transient improvement in both conditions following efgartigimod: a case report

Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia, most commonly mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with incompletely understood etiology, in which immune dysregulation has been implicated. Efgartigimod, the neonatal Fc receptor (FcRn) inhibitor approved for chronic/persistent ITP, accelerates IgG degradation by blocking IgG recycling via FcRn. We describe a patient with ITP and comorbid ALS in whom FcRn inhibition was temporally associated with transient improvement in both conditions. Case Description: A 66-year-old Japanese man with ALS diagnosed in March 2023 developed severe thrombocytopenia in September 2024, with a platelet count of 1.0×109/L and an elevated immature platelet fraction (18.1%). After differential diagnosis, ITP was diagnosed. Prednisolone and eltrombopag were ineffective. Intravenous efgartigimod (10 mg/kg) was initiated in October 2024 (day 0), resulting in a prompt platelet increase. Total IgG decreased from 1,643 to 858 mg/dL, and platelet-associated IgG normalized. During efgartigimod therapy, the revised ALS Functional Rating Scale (ALSFRS-R) score showed a subtle increase from 40 to 41 in January 2025 (day 83). After nine doses, efgartigimod was discontinued in January 2025 (day 91) and romiplostim was titrated with the goal of treatment cessation, but platelet counts remained unstable without remission. Unexpectedly, vital capacity increased from 81% to 93.9% in February 2025 (day 109). Thereafter ALS progressed and frequent clinic visits became difficult, romiplostim was replaced with eltrombopag and fostamatinib was added in June 2025 (day 238), resulting in stable platelet counts. In December 2025 (day 422, eleven months after efgartigimod discontinuation) total IgG increased to 1,499 mg/dL; platelet-associated IgG remained normal, however, ALSFRS-R declined to 31 and gastrostomy was required. Conclusions: This case documents concurrent ITP and ALS with transient improvement in platelet counts and ALS functional measures during FcRn inhibition with efgartigimod, followed by deterioration after discontinuation. Although causality cannot be inferred from a single case and neurologic changes may be coincidental, the temporal association raises the possibility that IgG-mediated immune mechanisms contribute to disease activity in a subset of ALS patients with autoimmune comorbidities. Further clinical and translational studies are warranted.