Date of Award

January 2020

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Richard Nowak

Abstract

Response to immunomodulatory therapies in myasthenia gravis (MG) can be variable. A subset of MG patients remains refractory to conventional agents. B-cell targeted therapy with rituximab has demonstrated a durable response in treating refractory myasthenia gravis (MG). This study compares the response to rituximab between patients with acetylcholine receptor autoantibody positive (AChR+) and muscle-specific kinase autoantibody positive (MuSK+) MG.

This retrospective study included 33 patients with either AChR+ or MuSK+ MG who were treated with rituximab from 05/31/2003 to 05/31/2017. Pretreatment and post-treatment immunotherapy regimens, clinical symptoms, and examination findings were evaluated.

Median MGFA Class of II at baseline improved to an asymptomatic median classification at 12-months and last follow-up (p-values <0.001) post-rituximab. Improvement in MGFA class was not significantly different between the groups. Twenty-one patients achieved clinical remission (12/17 AChR+, 9/16 MuSK+) with time to remission of 441.4 ± 336.6 days for AChR+ versus 230 ± 180.8 days for MuSK+ patients (p-value 0.049). The mean prednisone dosage requirement decreased significantly in both groups post-rituximab (p-value <0.01). AChR+ patients required more hospitalizations for exacerbation post-rituximab (p-value 0.046).

In conclusion, rituximab therapy is observed to have both a clinical benefit and durable response in the majority of AChR+ and MuSK+ MG patients with refractory disease, supporting the role of B cell depletion in the management of MG. While there was no significant difference between these groups in terms of clinical improvement, symptom-free state, and prednisone burden, MuSK+ MG patients may experience greater benefits, including earlier time to remission, fewer exacerbations and hospitalizations post-treatment.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 09/10/2022

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