Rituximab May Be More Effective in Early-Onset Myasthenia Gravis

Fredrik Piehl, MD, PhD, senior physician, Department of Clinical Neuroscience, Karolinska Institutet, and head of research, MS Clinic, Academic Specialist Center of Stockholm Health Services

Fredrik Piehl, MD, PhD

Data from a study of patients with myasthenia gravis who were exposed to rituximab at various points in the disease course, along with a control group, suggest that the anti-CD20 antibody performs better if initiated earlier after the onset of generalized symptoms.

All told, those who were treated with rituximab early had a shorter median time to remission (7 months) compared with those who had refractory disease (16 months; hazard ratio [HR], 2.53; 95% CI, 1.26—5.07; P = .009). Additionally, rituximab was associated with a shortened median time to remission (7 months) compared to conventional immunotherapy (11 months; HR, 2.97; 95% CI, 1.43—6.18; P = .004).

“Early treatment with rituximab may be associated with improved treatment outcomes and may be considered earlier in the treatment algorithms for patients with new-onset generalized myasthenia gravis,” study author Fredrik Piehl, MD, PhD, senior physician, Department of Clinical Neuroscience, Karolinska Institutet, and head of research, Multiple Sclerosis (MS) Clinic, Academic Specialist Center of Stockholm Health Services, and colleagues wrote.

Piehl and colleagues noted that as these clinical outcomes appear to favor rituximab in new-onset generalized myasthenia gravis, they believe that the data warrant a placebo-controlled randomized trial to corroborate these findings.

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The cohort study included 72 patients exposed to rituximab either early (within 12 months of onset; n = 24) or later (≥1 year after onset: n = 48) and a control group (n = 26) who received conventional immunotherapy (prednisolone, azathioprine, cyclosporine, tacrolimus, methotrexate, and mycophenolate mofetil). Of the group exposed to rituximab treatment later, 34 patients had refractory disease. The retrospective cohort study used prospectively collected data, conducted on a county-based community sample at Karolinska University Hospital.

The mean age for treatment initiation for the cohort was 60 years (standard deviation [SD], 18). For the control group, the mean age was 68 years (SD, 11) at treatment start. Piehl and colleagues noted that 3 patients received 1000-mg rituximab at the first infusion, 57 received 500-mg rituximab, and 12 received 100-mg rituximab. The subsequent infusions were given at a dose of 500 mg for all but 3 patients, who received 100-mg rituximab.

In addition to the apparent impact on early-onset disease, those treated with rituximab experienced fewer rescue therapy episodes during the first 2 years (mean, 0.38 [SD, 1.10]) compared to those on conventional therapy (mean, 1.31 [SD, 1.59]) for a mean difference of −1.26 episodes (95% CI, −1.97 to −0.56; P&thinsp;<.001), and a larger proportion of patients had minimal or no need of additional immunotherapy treatment (rituximab: 70%; conventional therapy: 35%; odds ratio [OR], 5.47; 95% CI, 1.40—21.43; P&thinsp;=&thinsp;.02).

The rates of treatment discontinuation due to adverse events (SEs) were also lower with rituximab (3%) compared with conventional therapies (46%; P&thinsp;<.001).

“A beneficial treatment response was observed with a lower rituximab dose than traditionally used (i.e., a single 500-mg infusion) vs the most used myasthenia gravis regimen of 4 separate infusions of 375-mg per month, although a recent noncontrolled study reported outcomes with a 600-mg dose,” Piehl et al. wrote. They acknowledged that in MS treatment, doses of 500 and 1000 mg displayed comparable effects on disease activity and B-cell depletion, writing that “even if extrapolation of data across diseases is not straightforward, it is possible that lower doses and avoiding exposure to combinations of immunosuppressants are associated with improved safety, not the least of which involves the risk of infections.”

They concluded that collectively, these data suggest that rituximab also should be considered earlier in the treatment algorithm for non-MuSK+ generalized myasthenia gravis, though the conclusions about its clinical effectiveness for patients with new-onset generalized disease must await results from an ongoing randomized clinical trial (NCT02950155), the results of which are anticipated in 2021.

REFERENCE

Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, Press R, Piehl F. Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis. JAMA Neurol. Published online May 4, 2020. doi: 10.1001/jamaneurol.2020.0851