New Study Examines the Risk of Relapse in Those Discontinuing MS Therapy

The discontinuation of high-efficacy therapies (HETs) that impact immune cell trafficking, including Tysabri (natalizumab; Biogen, Cambridge, MA) and Gilenya (fingolimod; Novartis, East Hanover, NJ), in people aged ≥50 years with nonactive multiple sclerosis (MS) was associated with a significantly increased risk of relapse. However, the discontinuation of other HETS, such as anti-CD20 HETs, including Ocrevus (ocrelizumab; Genentech, South San Francisco, CA) and rituximab was not associated with a significant increase in relapse risk. These findings, according to authors of a study published in JAMA Neurology, may inform decisions about stopping HET in certain patients.

The observational cohort study utilized data from June 2022 derived from 38 expert centers in the French MS registry database: the Observatoire Française de la Sclérose en Plaques (OFSEP). The study included 1620 people with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) who were aged ≥50 years, had been on HET, and showed no relapse or MRI activity for ≥2 years. Participants were separated into an HET discontinuation group (n=168) and an HET continuation group (n=1452). Dynamic propensity score (PS) was used to match 154 participants who discontinued with 154 participants who had an equal probability to discontinue but did not. The primary outcome measured was the time to first relapse, defined as the appearance, recurrence, or aggravation of neurological symptoms for ≥24 hours without fever.

In this study, HETs included:

• Gilenya (33% of matched participants)
• Tysabri (29% of matched participants
• Anti-CD20 therapy with Ocrevus or rituximab (38% of matched participants)

A total of 41 matched participants who discontinued HET experienced a relapse, whereas 9 matched participants experienced relapse in the therapy continuation group.

• Participants who discontinued HET showed a significantly reduced time to first relapse compared with those who continued treatment (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.5; P<.001).
• Only participants with RRMS were confirmed as having an increased probability of relapse (HR, 4.3; 95% CI, 2.0 to 9.4; P<.001).

Within the HET discontinuation group:

• Risk of relapse was significantly increased for Tysabi (HR, 7.2; 95% CI, 2.1 to 24.5; P=.001) and Gilenya (HR, 4.5; 95% CI, 1.3 to 15.5; P=.02).
• Risk of relapse was not significantly increased for those who discontinued antiCD20 therapy (HR, 1.1; 95% CI, .3 to 4.8; P=8.5)