Rituximab Could Treat Both Relapsing-Remitting and Progressive MS

While rituximab is frequently used off-label to treat relapsing-remitting multiple sclerosis (MS), emerging evidence suggests that patients with progressive MS may also benefit from treatment with rituximab.

In the absence of a randomized phase 3 comparative trial, researchers, reporting their findings in Plos One, sought to characterize patients with both relapsing-remitting and progressive MS treated in a single tertiary care center in Southern Switzerland to assess the effectiveness of the treatment versus natalizumab.

The researchers drew data from the center’s MS registry for patients with a diagnosis of MS, at least 1 recorded infusion of rituximab, and available clinical and radiological follow-up data. In total, there were 43 evaluable patients with relapsing-remitting disease and 39 with progressive disease (27 with secondary and 12 with primary progressive disease). The primary reasons that patients switched to rituximab in both groups was disease progression.

All patients underwent an initial induction regimen of 1 infusion on day 1, followed by a second infusion on day 15. The dose of rituximab was 1000 mg in 74 (91.4%) patients and 500 mg in 7 (8.6%) patients. The induction period was followed by a third infusion at month 9, then every 6 months thereafter. The maintenance dose was 1000 mg in 72 (87.8%) patients and 500 mg in 10 (12.2%) patients.

The researchers found that the total number of relapses observed during rituximab treatment was 3 (median followup, 1.5 years; range, 1.0-2.5 years), and all occurred in patients with progressive disease (at months 6, 12, and 18, respectively). Expanded disability status scale (EDSS) worsening was observed in 7 (16.3%) and 8 (20.5%) patients in the relapsing-remitting and progressive groups, respectively, with no statistically significant difference between the groups.

The median time between baseline MRI and last follow-up MRI was 12 months (range, 10-24) for the relapsing-remitting group and 18 months (range, 12-29) for the progressive group. New T2 brain lesions were present in 5 patients in the relapsing-remitting group and 1 patient in the progressive group.

Overall, the proportion of patients without evidence of disease activity was 75.6% overall (77.5% in the relapsing-remitting group, and 73.7% in the progressive group).

The authors included patients treated with natalizumab in their analysis for comparison with rituximab-treated patients; they found no significant difference between patients with relapsing-remitting disease treated with rituximab versus those treated with natalizumab in terms of time to evidence of disease activity (after correcting for age, sex, baseline EDSS, new T2 lesions at baseline MRI, and number of relapses in the 2 years before starting treatment).

The number of clinically significant infusion-related adverse events (AEs) was 10 (of 339 rituximab infusions), including fever, myalgia, nausea, tachycardia, and swelling of buccal mucosa. Non-infusion AEs included respiratory tract infections, urinary infections, and shingles. Ten patients reduced their dosages because of recurrent infections, and 9 patients discontinued treatment. Reasons for discontinuation were disability progression in 3 patients and recurrent infections in 6 patients.

The authors concluded that their study provides additional evidence that supports the use of rituximab in MS, given its comparable effectiveness to natalizumab in relapsing-remitting disease and its potential benefit for hard-to-treat progressive diseases. Rituximab could provide, say the authors, “an additional effective, relatively cheap and safe therapy in the panel of existing MS treatments.”

Reference

Scotti B, Disanto G, Sacco R, Guigli M, Zecca C, Gobbi C. Effectiveness and safety of rituximab in multiple sclerosis: an observational study from Southern Switzerland [published online May 14, 2018]. Plos One. doi: 10.1371/journal.pone.0197415.