A Two-Year Retrospective Analysis of Rituximab Therapy in Secondary-Progressive MS

Background: While mitoxantrone is the only FDA approved drug to treat SPMS, its use is limited by high toxicity. As growing literature has supported a role of B-cell activity in SPMS patients, there has been interest in the potential of rituximab therapy.  B cell depletion by rituximab has demonstrated safety in phase 1 and phase 2 studies for relapsing-remitting MS. 

Objectives: The goal of this study is to evaluate retrospectively the clinical outcomes in patients with secondary-progressive multiple sclerosis (SPMS) treated with rituximab.

Methods: In this study, EDSS, twenty-five foot walk, and nine-hole peg test scores were evaluated for 30 SPMS patients on rituximab therapy in the past two years at the University of Massachusetts MS Center. Patient data was stratified according to specific treatment number, ranging from 1-3. To perform a within-subjects analysis, baseline scores for each patient were obtained from clinical visits one year prior to treatment initiation. These values were also compared to measures from each patient two years prior to treatment to establish a rate of  progression. The efficacy of other treatments in controlling progression through each patient’s course were compared to rituximab therapy across the three outcome measures. Further, because of individual variability in response (improvement, stability) or no response (progression) to therapy, subgroup analysis was performed as a step toward identifying characteristics of responders and non-responders.  MRI data was used to monitor safety and any adverse reactions were noted.

Results: Over two years prior to treatment, there were statistically significant increases in EDSS as well as increases in twenty-five foot walk and nine-hole peg test scores, reflecting progression. In contrast, following initiation of rituximab treatment, no significant differences were found relative to baseline values, suggesting that patients were at least stabilized on therapy. A comparison of mean scores across subsequent treatments of rituximab demonstrated a tendency toward improvement of EDSS. Comparison of the different drug regimens across EDSS, twenty-five foot walk, and nine-hole peg test revealed that rituximab was best able to maintain baseline measurements. Subgroup analysis of patients’ EDSS scores demonstrated that a majority responded to rituximab therapy, with 48% achieving stability and 36% experiencing a statistically significant improvement. Patients who improved also tended to have lower EDSS scores. There were no changes in MRI activity for patients through their course of treatment, except for one non-enhancing lesion in one patient. No significant adverse reactions were reported.

Conclusions: These data support that rituximab therapy in treatment of SPMS could stabilize, and potentially reverse, the rate of disease progression. However, in developing this potential therapy, more support for these results must be achieved through larger studies.