Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study Tess Litchman a,1 , Bhaskar Roy a,1 , Aditya Kumar a , Aditi Sharma a , Valentine Njike b , Richard J. Nowak a,⁎ a YaleSchoolofMedicine,DepartmentofNeurology,NewHaven,CT,USA b Griffin Hospital-Derby, Yale University Prevention Research Center, Derby, CT, USA ARTICLE INFO Keywords: Myasthenia gravis Rituximab Immunotherapy B cell depletion ABSTRACT Background: B-cell targeted therapy with rituximab has shown durable response in treating refractory myas- thenia 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. Methods: 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. Results: Median MGFA Class of II at baseline improved to an asymptomatic median classification at 12-months and last follow-up (p-values <.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. AChR+ pa- tients required more hospitalizations for exacerbation post-rituximab (p-value 0.046). Conclusion: Rituximab treatment response is observed in both AChR+ and MuSK+ patients 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 experi- ence greater benefits, including earlier time to remission, fewer exacerbations and hospitalizations post-treat- ment. 1. Introduction Myasthenia gravis (MG) is an autoimmune disorder of the neuro- muscular junction, leading to muscular weakness and fatigue. Antibodies to the acetylcholine receptor (AChR) are detected in up to 80% of patients, with up to 40% of patients who lack antibodies to AChR having antibodies to muscle-specific kinase (MuSK) [1–3]. Treatment typically includes symptom management with acet- ylcholinesterase inhibitors as well as immunotherapy, including agents such as corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, plasma exchange (PLEX), and intravenous immunoglobulin (IVIg) [4–6]. Thymectomy, with or without thymoma, has also been shown to be beneficial in the treatment of generalized AChR+ MG [7]. Response to immunomodulatory therapies in myasthenia gravis (MG) can be variable. A subset of MG patients remains refractory to con- ventional agents [8]. B-cell targeted therapy with rituximab has shown durable response in treating refractory MG. The benefits of rituximab in MG have been reported by several groups [9–18]. Treatment of MG with rituximab has been shown to result in sustained clinical im- provement, as well as allowing for tapering and discontinuing of other immunotherapies [9,19]. A recent phase 2 clinical trial of rituximab in AChR+ MG (BeatMG Study) demonstrated a favorable safety profile, however, met the primary futility outcome at 52-weeks suggesting that there would be a low probability of achieving the prespecified steroid sparing effect difference in a similar mildly symptomatic cohort on concomitant immunotherapy [20,21]. This study was not limited to refractory disease or powered to assess efficacy. A multicenter blinded, prospective review of MuSK+ MG demonstrated better clinical https://doi.org/10.1016/j.jns.2020.116690 Received 24 July 2019; Received in revised form 20 December 2019; Accepted 17 January 2020 ⁎ Corresponding author at: Yale University School of Medicine, Department of Neurology, Division of Neuromuscular Medicine, Program in Clinical & Translational Neuromuscular Research (CTNR), PO Box 208018, New Haven, CT 06520, USA. E-mail address: richard.nowak@yale.edu (R.J. Nowak). 1 These authors contributed equally Journal of the Neurological Sciences 411 (2020) 116690 Available online 18 January 2020 0022-510X/ © 2020 Elsevier B.V. All rights reserved. T