Date of Award

January 2020

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Richard Nowak


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.


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