For patients with relapsing-remitting multiple sclerosis (RRMS) switching to other therapies due to positive JC virus serology, treatment with rituximab resulted in a lower rate of clinical relapse as compared with fingolimod in a retrospective outcomes study of registry data from three Swedish MS centers, according to a report published online March 31 in Annals of Neurology.
Although natalizumab (Tysabri) is approved for the treatment of highly active RRMS, its long-term use can increase the risk of developing progressive multifocal leukoencephalopathy. Because this is a serious and potentially lethal condition associated with opportunistic brain infection with the JC virus, those patients testing positive for JC virus antibodies may require a switch to an alternative treatment, such as fingolimod (Gilenya), or off-label use of rituximab (Rituxan). The efficacy, safety, and tolerability associated with switching to either of these alternative therapies were compared by Peter Alping of the department of clinical neuroscience, Karolinska Institutet, Stockholm, and his associates (Ann Neurol. 2016 Mar 31. doi: 10.1002/ana.24651).
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Of the 256 patients included in the study, 142 (55%) were switched to fingolimod. The efficacy outcomes comparison showed a statistically significant difference in favor of rituximab, with which 2% of patients had a clinical relapse in the first 1.5 years of treatment after natalizumab cessation as opposed to 18% for fingolimod. This corresponded to an annual relapse rate of 0.02 and 0.16, respectively. Additionally, a review of patients’ contrast-enhancing lesions on MRI scans after at least 3 months of treatment indicated that disease progression was detected less frequently in patients switched to rituximab (1%) as opposed to those switched to fingolimod (16%).
The safety and tolerability data also indicated more favorable results for those patients switched to rituximab. For example, a significantly lower rate of adverse events was noted in the rituximab group (5%) when compared with the fingolimod group (21%). Similarly, a lower rate of treatment discontinuation was observed for those switched to rituximab (2%) when compared with those switched to fingolimod (28%).
The statistically significant differences found in the efficacy, safety, and tolerability data persisted even after adjusting for possible confounding factors including patient age, sex, disability status, time on natalizumab, washout time, follow-up time, and study center. Despite the differences noted in the safety findings, the authors said that both treatments seemed to be safe in general.
In most cases, natalizumab had been given 300 mg IV every 4 weeks. Fingolimod was given orally 0.5 mg once daily. Nearly all patients who received rituximab got a single IV infusion of 500 or 1,000 mg every 6 months, but in some cases the first infusion had been repeated after 2 weeks.
In the absence of formal randomized clinical trial data, the authors said that these findings support the use of rituximab over fingolimod in this particular population of MS patients.
This study was supported by the Swedish Medical Research council and the Stockholm County. First author Peter Alping declared no competing interests; several of his associates reported ties to numerous industry sources.