Observational studies have allowed researchers to compare the effectiveness and safety of traditional treatment options for multiple sclerosis and rituximab.
Multiple sclerosis is a chronic immunological disease affecting the central nervous system. Depending on the region of the brain affected by the disease, patients may experience a wide range of symptoms (i.e. vision problems, bladder issues, movement disabilities, sexual dysfunction) that will worsen progressively with time. Drug therapy has expanded over the last few years with the addition of new disease-modifying therapies. However, these traditional therapies are associated with a high level of discontinuation. Rituximab is traditionally used for rheumatoid arthritis; nevertheless, recently it has been used off-label in Sweden for multiple sclerosis.
Swedish researchers at the Karolinska Institutet’s Department of Clinical Neuroscience in Stockholm had a unique opportunity to conduct a comparative real-world effectiveness study on rituximab for multiple sclerosis. The results of this study were published in the Journal of the American Medical Association Neurology.
The Swedish multiple sclerosis registry contains data on 14,500 patients with multiple sclerosis. Among these, 494 newly diagnosed patients were included in the study. Patients were using either rituximab, injectable disease-modifying therapies, dimethyl fumarate, fingolimod, or natalizumab. Considering the real-world nature of this observational study, the baseline characteristics differed among the patients receiving different drug therapies. The primary outcome of the study was the discontinuation of the prescribed drug and the reason for stopping therapy was also included in the analysis. Other outcomes included side effects, the presence of brain lesions on MRI scans, and disease relapse.
Fewer Discontinuations in the Rituximab Group
Compared with patients on traditional treatment (injectable disease-modifying therapies, dimethyl fumarate, fingolimod, and natalizumab), the proportion of patients continuing therapy was significantly higher in the rituximab group. Patients treated with injectable disease-modifying therapies, dimethyl fumarate, and fingolimod discontinued treatment more often because of disease relapse or side effects. Rituximab-treated patients discontinued more often because of pregnancy and only 0.8% of patients discontinued therapy because of disease breakthrough. Positive JC virus blood results were the most common reason for discontinuing natalizumab among patients in the study.
The secondary outcome, relapse rates, was lower with rituximab compared with injectable disease-modifying therapies. No significant differences were noted when comparing relapse rates between rituximab-treated patients and those receiving dimethyl fumarate or fingolimod. Rituximab also resulted in a lower outcome of brain lesions when compared with injectable disease-modifying therapies and dimethyl fumarate. The side effect profile did not differ significantly between the groups treated with rituximab, fingolimod, and natalizumab. Injectable disease-modifying therapies demonstrated more mild intensity side effects when compared with rituximab, but the low rate of moderate to severe side effects was comparable in both treatment groups.
This observational study demonstrated that rituximab, although considered an off-label therapy for multiple sclerosis, has a lower rate of discontinuation and relapse rate. Further studies with a larger patient population are required to confirm the effectiveness and safety of rituximab in multiple sclerosis patients.
Written by Jessica Caporuscio, PharmD
(1) Granqvist M, Boremalm M, Poorghobad A, et al. Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurol. 2018
(2) Hillert J, Stawiarz L. The Swedish MS registry – clinical support tool and scientific resource. Acta Neurol Scand. 2015.