Disability Progression after Switching from Natalizumab to Fingolimod or Injectable Therapies: A NARCOMS Analysis

Background: Natalizumab (NAT) is a highly effective treatment for MS. The clinical outcomes of NAT-treated patients who switch to other treatments are not well understood.

Objectives: Compare changes in patient-reported disability progression measured by Patient Determined Disease Steps (PDDS) between NAT-treated patients who remained on NAT and those who switched treatment after a minimum of 2 years of NAT use.

Methods: A total of 547 NARCOMS participants had ≥2 years of continuous NAT treatment and ≥1 follow-up survey that included a PDDS assessment. Changes in PDDS scores from the first survey indicating NAT treatment until final survey were compared between participants whose only disease modifying treatment during follow-up was NAT (N=406) and those who switched treatment to fingolimod (FIN) (N=50; follow-up post-switch, mean [SD]=15.0 [10.4] months) or to injectable therapies (INJ [interferon-beta or glatiramer acetate]) (N=71; follow-up post-switch=20.4 [13.9] months). Participants were excluded who switched to other treatments (N=10) or who lacked PDDS assessment in the first survey during NAT treatment (N=10). Median group characteristics were compared with Wilcoxon, mean PDDS change with covariate adjusted ANOVA, and proportion of patients with PDDS increase with Likelihood Ratio Test.

Results: Age, gender, and starting PDDS were similar in all groups (all p>0.05); median months of total follow-up were significantly different (NAT=48; FIN=54; INJ=60; p<0.0001). Age, gender, and starting PDDS were associated with change in PDDS (all p<0.03); total follow-up time was not (p=0.69). Adjusted mean PDDS was not different between groups after 2 years of NAT therapy (p=0.11), but at the end of follow-up the mean PDDS increase was 0.31 points for NAT, 0.58 for FIN, and 0.71 for INJ; the difference between NAT and INJ groups was significant (p=0.007). In addition, there was a difference between groups in the proportion of participants with ≥1 point increase in PDDS (NAT=30.8%; FIN=46.0%; INJ=42.3%; p=0.03) with an odds ratio of 1.9 for FIN vs NAT (p=0.03) and 1.6 for INJ vs NAT (p=0.06).

Conclusions: On average, those that switched to INJ reported larger disability increases than those remaining on NAT. Switching from NAT to FIN or INJ was associated with an increased likelihood of reported disability progression. While disability was similar during 2 years of natalizumab and differed over time including treatment switch, causality cannot be concluded.