Rituximab More Beneficial if Given to gMG Patients Early, Study Finds
Investigators also noted that among newly-diagnosed patients, rituximab seems to be superior to other conventional immunosuppressive regimens.
The study, “Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis,” was published in the journal JAMA Neurology.
MG is caused by the abnormal production of antibodies that wrongly target proteins necessary for muscle contraction. The most severe form of the disease is gMG, in which the typical symptoms of weakness and fatigue may affect all muscles in the body.
Conventional treatments for MG usually include corticosteroids and other types of immunosuppressants that help reduce the overactivation of the immune system and the production of harmful self-reactive antibodies.
However, many patients become refractory and fail to respond to conventional treatment regimens.
“Given the heterogeneity [diversity] of MG, it is likely that additional biologic agents, some of which may already be approved for other conditions, can be effective,” investigators wrote.
Rituximab — marketed by Genentech and Biogen in the U.S. under the brand name Rituxan — is one of these biologic agents, being used to treat cancer and autoimmune diseases such as rheumatoid arthritis.
The medication is an antibody that targets B-cells — immune cells responsible for the production of antibodies — reducing their numbers. By lowering the levels of overactive immune cells and the harmful antibodies they produce, rituximab potentially may slow MG progression, ease symptoms, and reduce the need for more aggressive treatments.
However, studies assessing the potential benefits of biologics in gMG patients usually focus on people with refractory disease, instead of newly-diagnosed individuals. In particular, prior research indicated potential benefits of rituximab in MG patients with refractory disease and with anti-MuSK autoantibodies.
To investigate the potential benefits of rituximab in both groups, researchers in Sweden reviewed the medical records of gMG patients who were registered at the National MG registry.
All patients residing in Stockholm who started treatment with rituximab from January 2010 to December 2018 — usually low-dose rituximab (500 mg, every six months) — were included in the analyses. The study also included those who were newly-diagnosed and started conventional immunotherapy from January 2003 to December 2012.
In total, 72 gMG patients — 31 women and 41 men, with a mean age of 60 years at the time they started treatment — were included. No participant had anti-MuSK autoantibodies.
Twenty-four received rituximab within the first year following the onset of gMG. From the 48 patients who started treatment with rituximab at a later time, 34 had refractory disease.
The study also included 26 newly-diagnosed patients who received conventional treatment, who served as a control group.
After adjusting data for age, sex and disease severity, investigators found that newly-diagnosed patients entered remission faster compared to the refractory gMG (median time to remission of seven vs. 16 months).
Results also showed that newly-diagnosed patients who were on rituximab entered remission faster than people receiving conventional immunotherapy — median time to remission seven vs. 11 months. In addition, the proportions of patients in clinical remission at one (87% vs. 58%) and two years (96% vs. 62%) were larger with rituximab than with conventional immunotherapies.
Patients on rituximab required fewer rescue therapies during the first two years compared to the control group (0.38 vs. 1.31 times).
Researchers also found that 70% of patients receiving rituximab had minimal or no need for additional immunotherapies, which compared to 35% of patients receiving conventional treatment who achieved the same outcome.
Safety assessments also showed that the rates of treatment discontinuation due to adverse events (side effects) were lower among people receiving rituximab compared to conventional immunotherapies (3% vs. 46%).
“The results of this retrospective cohort study of rituximab-treated patients with (…) gMG suggest that initiation of therapy early after diagnosis may be associated with improved outcomes and good tolerability compared with treatment with conventional immunotherapies,” the investigators wrote.
They also added that an ongoing Phase 3 trial (NCT02950155) investigating the safety and efficacy of rituximab in newly-diagnosed gMG patients should provide more conclusive evidence on the therapy’s effectiveness in this group of patients. Top-line findings from the study are expected by January 2021.