New Model for Treatment of ALS Pseudo-progression in SOD1-associated ALS With Tofersen
Shokufeh Sadaghiani1, Nathan Carberry2
1Neurology, University of Miami, 2Univsersity of Miami
Background:
Tofersen is a new genetic therapy for Superoxide Dismutase 1 (SOD1) Amyotrophic Lateral Sclerosis (ALS), and myelitis is a known adverse event reported in approximately 7% of patients. Myelitis can mimic ALS progression as ALS “pseudo-progression.” If detected, the management currently involves discontinuation of Tofersen, which deprives patients of the medication’s survival benefits. Here, we present a case that was successfully managed without discontinuing Tofersen.
Design/Methods:
A 58-year-old woman with genetically confirmed SOD1 mutation was diagnosed with ALS at the University of Miami in May 2023. Intrathecal Tofersen was started in July 2023 and she experienced stabilization of her respiratory decline and normalization of her neurofilament light chain (NfL) level.
Following 14th dose, she developed progressive sensorimotor deficits in her legs. She was diagnosed with myelitis after MRI showed multiple Gadolinium-enhancing lesions throughout the cervical and thoracic spinal cord. She received a single dose of intrathecal hydrocortisone 50 mg and intravenous methylprednisolone 1 g daily for 5 days, resulting in significant improvement in her sensorimotor symptoms.
Tofersen along with 50 mg intrathecal methylprednisolone was resumed 5 weeks after her last dose. However, her myelitis recurred, and she was treated with intravenous rituximab (two doses of 1000 mg, two weeks apart), which led to complete resolution of symptoms back to baseline. Tofersen was restarted in addition to a combination of intrathecal steroid and maintenance Rituximab, and she remains with normal NfL and without myelitis or significant ALS progression.
Conclusions:
Tofersen-induced myelitis is a form of ALS pseudo-progression which can lead to early termination of the life-saving medication. In this patient, early recognition and treatment with intrathecal steroids and rituximab led to a favorable long-term outcome. This highlights the importance of recognition of this adverse effect as well as a novel treatment paradigm to avoid discontinuing Tofersen.
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