More than 80% of individuals with multiple sclerosis ( MS ) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting multiple sclerosis ( RRMS ) convert to secondary progressive MS.
Alternative and more effective multiple sclerosis treatments with new modes of action and good safety are needed to expand the current treatment repertoire.
It has been shown that B lymphocytes are involved in the pathophysiology of multiple sclerosis and Rituximab ( MabThera, Rituxan ) lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity.
Current clinical trials are evaluating the role of Rituximab as a B-cell depletion therapy in the treatment of relapsing-remitting multiple sclerosis.
The safety and effectiveness of Rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs ( DMDs ) ( Interferon-beta, Glatiramer acetate, Natalizumab, Mitoxantrone, Fingolimod, Teriflunomide, Dimethyl fumarate, Alemtuzumab ) to reduce disease activity for people with relapsing-remitting multiple sclerosis were assessed.
All randomised, double-blind, controlled parallel group clinical trials with a length of follow-up equal to or greater than one year evaluating Rituximab, as monotherapy or combination therapy, versus placebo or approved DMDs for patients with relapsing-remitting multiple sclerosis without restrictions regarding dosage, administration frequency and duration of treatment, were identified.
One trial involving 104 adult RRMS patients with an entry score less than or equal to 5.0 on the EDSS ( Expanded Disability Status Scale ) and at least one relapse during the preceding year was included.
This trial evaluated Rituximab as monotherapy versus placebo, with a single course of 1000 mg intravenous rituximab ( on day 1 and day 15 ).
A significant attrition bias was found at week 48 ( 24.0% ).
Patients receiving Rituximab had a significant reduction in total number of Gadolinium-enhancing lesions at week 24 ( mean number 0.5 versus 5.5; relative reduction 91% ) and in annualised rate of relapse at week 24 ( 0.37 versus 0.84 ) but not at week 48 ( 0.37 versus 0.72 ).
Disability progression was not included as an outcome in this trial.
More patients in the Rituximab group had adverse events within the 24 hours after the first infusion ( 78.3% versus 40.0% ), such as chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to-moderate events ( 92.6% ).
The most common infection-associated adverse events ( greater than 10% in the Rituximab group ) were nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. Among them, only urinary tract infections ( 14.5% versus 8.6% ) and sinusitis ( 13.0% versus 8.6% ) were more common in the Rituximab group.
In conclusion, there is not sufficient evidence to support the use of Rituximab as a disease-modifying therapy for relapsing-remitting multiple sclerosis because only one RCT was included. The quality of the study was limited due to high attrition bias, the small number of participants, and short follow-up.
The beneficial effects of Rituximab for relapsing-remitting multiple sclerosis remain inconclusive.
However, short-term treatment with a single course of Rituximab was safe for most patients with relapsing-remitting multiple sclerosis. Mild-to-moderate infusion-associated adverse events were common, as well as nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis.
The potential benefits of rituximab for treating relapsing-remitting multiple sclerosis need to be evaluated in large-scale studies that are of high quality along with long-term safety. ( Xagena )
He D et al, Cochrane Database Syst Rev 2013; 12:CD009130. doi: 10.1002/14651858.CD009130.pub3