Rituximab outperforms fingolimod after natalizumab switch

By Lucy Piper

Rituximab is more effective and better tolerated than fingolimod for patients with multiple sclerosis (MS) needing to switch from natalizumab due to JC-virus (JCV) antibody positivity, research suggests.

Among 256 patients from three Swedish MS centres, just two (1.8%) of 114 patients switched to rituximab experienced a clinical relapse within 1.5 years, compared with 25 (17.6%) of 142 patients switched to fingolimod, giving a significant crude hazard ratio in favour of rituximab of 0.10.

The benefit of continued natalizumab treatment in patients who test positive for the JCV antibody has to be carefully weighed against the risk of progressive multifocal leukoencephalopathy and the return of disease activity on discontinuation effectively managed, explain Fredrik Piehl (Karolinska University Hospital, Stockholm, Sweden) and co-researchers.

Switching to rituximab treatment was associated with a lower likelihood of developing contrast-enhancing lesions, occurring within 1.5 years in one (1.4%) of 69 rituximab-treated patients with valid scans versus 23 (24.2%) of 95 fingolimod-treated patients, giving a significant odds ratio of 0.05.

"The better drug survival of [rituximab] seemed to be mainly a result of its greater effectiveness, as most discontinuations on [fingolimod] were due to disease breakthrough", the team notes in the Annals of Neurology.

Among 42 patients who discontinued treatment during the first 1.5 years, two were taking rituximab and 40 were taking fingolimod, giving yearly discontinuation rates of 0.02 and 0.24, respectively, and a significant hazard ratio for time to discontinuation of 0.07 after adjusting for confounders such as age, gender, disability status, time on natalizumab and washout period.

"Another contributing reason was that [rituximab] was better tolerated than [fingolimod] in this patient population, in spite of a higher rate of first-time infusion AEs [adverse events] compared with first-dosing AEs for [fingolimod]", they add.

First-dosing AEs, all grade 1, occurred in 26% of patients in the rituximab group compared with 7% of those in the fingolimod group. But the occurrence of AEs declined over time with the final rates 5% in patients taking rituximab and 21% for patients taking fingolimod.

For the former group, AEs tended to be of grade 1 with only one case each of grade 2 bronchial infection and grade 3 enterocolitis infection, compared with eight grade 2 and two grade 3 events in patients taking fingolimod plus one potentially life-threatening grade 4 laryngeal oedema event.

"The results provide a strong motive for a formal [randomised controlled trial] with [rituximab] or another anti-CD20 monoclonal in the context of patients switching from [natalizumab]", says the team.

"In the absence of such data, [rituximab] appears to be the superior choice, compared with [fingolimod], in this patient population."

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