Switching From Natalizumab to Fingolimod in Multiple Sclerosis

Abstract

IMPORTANCE The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge.OBJECTIVE To collect data from patients with MS switching from natalizumab to fingolimod. DESIGN, SETTING, AND PARTICIPANTSThe Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. MAIN OUTCOMES AND MEASURESOccurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod.RESULTS Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). CONCLUSIONS AND RELEVANCEIn this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.

Neurological safety of fingolimod: An updated review

“…However, there is no established guideline on an appropriate washout period between NTZ and FTY. A study in a French prospective cohort recommended a washout period shorter than 3 months,86 whereas a large prospective international registry advised a maximum 2‐month treatment gap for switches to FTY to reduce the risk of relapse 87. These studies suggest that a prolonged washout period might do more harm than good, and washout should be no longer than 2 months.…”

Natalizumab to Fingolimod Switching in Multiple Sclerosis: Results from a “Real Word” Retrospective Analysis

“…Results from the ENIGM study [9] in 333 patients switching from natalizumab to fingolimod (69.1% patients underwent a 6-month follow up) highlighted the importance of a natalizumab washout duration of less than 3 months, as these patients had a significantly lower risk of relapse than those who underwent a longer washout period. Despite having a similar proportion of relapsing patients, in subgroup with the same washout length, we did not find a relationship between the washout length and the relapse rate, perhaps due to the small number of patients in our study.…”

“…Fingolimod (Gilenya, Novartis, Basel, Switzerland) is an option for these patients [1,3,[8][9][10][11][12] however, because of the still unknown impact on the immune system of the concomitant presence of these molecules, an interval is recommended between discontinuing natalizumab and starting fingolimod. Studies investigating switching from natalizumab to fingolimod have shown clinically relevant disease activity during the first weeks of fingolimod treatment, challenging its effectiveness in this setting, and highlighting the need to clarify its role in patients with a disease characterized by its severity and rapid evolution, and to improve the switching protocol [9,11].…”

“…Although this topic has been largely discussed in literature [9,11,12], the current study aims in providing a descriptive analysis of a large cohort of patients followed for many years. Indeed, while previous research only considered patient's clinical course in the previous year, the objective of this study is to describe the patients' whole disease course and to analyse predictive factors for disease relapse.…”

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

“…The obvious candidate in this situation appears to be fingolimod which was recently shown to be advantageous over injectables after cessation of natalizumab [98], but is probably clinically less potent than natalizumab. Furthermore, some recent data strongly suggest that a switch from natalizumab to fingolimod may be associated with an increased risk of developing new disease activity [99,100]. A recent report came to the conclusion that too-long washout phases between natalizumab discontinuation and fingolimod initiation may elevate that risk and recommends waiting 4-8 weeks between treatments [101].…”