Rituximab Offers Hope for Refractory Myasthenia Gravis
Sixty-three percent of patients achieved a complete and stable response that allowed them to discontinue all immunotherapies.
In a study of the durability of rituximab treatment in refractory myasthenia gravis (MG), 63% of patients achieved a complete and stable response that allowed them to discontinue all immunotherapies. Another 19% achieved pharmacologic remission, and the remaining 19% reached minimal manifestation status (MMS) that did not require subsequent treatment for at least 1 year.
Rituximab treatment, given to patients with refractory acetylcholine receptor autoantibody positive (AChR+) MG, produced a significant response in all 16 participants of a study led by Kimberly R. Robeson, MD, of the Program in Clinical and Translational Neuromuscular Research at Yale School of Medicine, along with others from the Hospital of Special Surgery in New York.1 The participants were followed for 18 to 84 months after the initial rituximab cycle and given up to 4 cycles of treatment as needed to maintain clinical response.
Disease was defined as refractory if remission could not be achieved despite therapy, if the remission could not be maintained through a reduction of the current therapeutic dose, or in cases where the adverse effects contraindicated the continuation of traditional immunosuppressive therapy.
Nicholad J. Silvestri, MD and Gil I. Wolfe, MD, of the State University of New York, Buffalo in an accompanying editorial,2 noted that 10 to 15% of MG patients have “difficult-to-control disease” despite effective treatment with acetylcholinesterase inhibitors, corticosteroids, or corticosteroid sparing agents (eg, azathioprine and mycophenolate mofetil). Rituximab is a chimeric anti-CD20 monoclonal antibody that targets autoreactive B cells, which have been implicated in the pathophysiology of MG and other autoimmune diseases.1,3 A series of earlier studies4-6 demonstrated the efficacy of rituximab in drug-resistant MG (defined as failure of at least 3 therapies) as well as refractory MG, but without indication of the duration of response.
In the current study, Dr Robeson and colleagues reported that 56% of the patients (n= 9) relapsed at a mean of 36 months after the initial rituximab treatment; however, remission was reinstated with a subsequent dose. Ultimately, 8 patients showed an extended durable response after 2 cycles of rituximab, 7 patients with 3 cycles, and 1 patient with 4 cycles. Most patients required a least a year to completely withdraw from immunotherapy in order to demonstrate a clinical remission.
The authors reported initial observations that patients who had more cycles of therapy tended to have a greater durability of response, but suggested the need to repeat these results in a larger cohort. “Biomarkers would be very helpful in guiding clinicians as to whom to offer additional cycles,” they concluded.
- Robeson KR, Kumar A, Keung B, et al. Durability of the rituximab response in acetylcholine receptor autoantibody–positivemyasthenia gravis. JAMA Neurol. 2016; doi: 10.1001/jamaneurol.2016.4190 [Epub ahead of print]
- Silvestri NJ, Wolfe GI. Rituximab in Treatment-Refractory Myasthenia Gravis. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.4190 [Epub ahead of print]
- Zebardast N, Patwa HS, Novella SP, et al. Rituximab in the management of refractory myasthenia gravis. Muscle Nerve. 2010;41(3):375-378.
- Lebrun C, Bourg V, Tieulie N, et al. Successful treatment of refractory generalized myasthenia gravis with rituximab. Eur J Neurol. 2009;16(2):246-250.
- Díaz-Manera J, Martínez-Hernández E, et al. Long-lasting treatment effect of rituximab in MuSKmyasthenia. Neurology. 2012;78(3):189-193.
- Anderson D, Phan C, JohnstonWS, Siddiqi ZA. Rituximab in refractorymyasthenia gravis: a prospective, open-label study with long-term follow-up. Ann Clin Transl Neurol. 2016;3(7):552-555.