Fingolimod Shows Slight Long-Term Preservation of Cognition in Multiple Sclerosis

Serkan Ozakbas, MD

Fingolimod (Gilenya; Novartis), an FDA-approved disease modifying therapy (DMT) for patients with multiple sclerosis (MS), demonstrated a high rate of treatment continuation at 5 years and statistically significantly decreased the rate of patients demonstrating impairment on several cognitive assessments in a recent study.

Lead author Serkan Ozakbas, MD, Department of Neurology, Dokuz Eylul University, and colleagues conducted a multicenter, prospective study that followed 376 patients with relapsing-remitting MS who initiated fingolimod treatment from 2011 to 2014 for at least 5 years. When the study group was evaluated in 2019, the treatment showed positive long-term retention rates, indicated by 82.2% (n = 309) of patients who continued the therapy.

The primary way to evaluate cognition was through the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), a specific, sensitive, and widely used MS clinical battery. Other methods such as the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk (T25FW) were also used to evaluate the patients’ physical and cognitive function before and after treatment in the second and fifth years.

Prior to initiation of treatment, patients had EDSS scores of 2.43 (±2.1 [range, 0-5.5]). At the end of the second and fifth years, patients demonstrated scores of 2.39 (±1.4 [range, 0-5.5]) and 2.28 (±2.2 [range, 0-6.0]), respectively. Although there were no statistically significant differences between the evaluations, the EDSS scores did tend to decrease.

"Even the absence of a significant change in 3 parameters for 5 years is an important result and suggests that fingolimod has a significant impact on the physical disability that MS may cause," Ozabas et al wrote. "Moreover, improvements in both upper and lower extremity functions and their continuation indicated that MS disease progression may be slowed in most patients with fingolimod."

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In the fifth year of treatment, investigators observed a statistically significant decrease from the baseline evaluation in 9-HPT, which evaluated upper limb function (P = .042). For the T25FWT, which evaluated patients’ lower extremity functions, a significant improvement occurred in the second year of treatment compared to the pretreatment baseline. Notably, there was no significant difference between the measurements at the end of the fifth year.

Of the cohort, 202 patients (56.7%) switched to fingolimod because of their prior treatment’s ineffectiveness, while 154 (43.3%) switched due to side effects or personal desire. There was a statistically significant improvement in Symbol Digits Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R) results in the second year compared to the pretreatment period in the adverse effects group (P = .024; P = .004, respectively) that continued in the fifth year (P = .009; P = .008, respectively).

Despite not reaching statistical significance in the second year, investigators observed differences in California Verbal Learning Test-second edition (CVLTII) that became statistically significant in the fifth year (P = .018). Among those who switched to fingolimod due to first-line DMT ineffectiveness, there was no significant improvement in cognitive tests in the second year; although, by the fifth year there was a statistically significant improvement in CVLTII (P = .045) and BVMT-R (P = .04).

Prior to initiation of treatment, the rate of cognitive impairment (CI) in any of the 3 BICAMS subsets was 49.7%. At the end of the fifth year, that rate dropped to 44.1%. The combined pretreatment rate of CI in all subsets was 19.7%, which statistically significantly decreased to 15.2% at the end of the fifth year (P = .008). Notably, the improvement occurred in both the group that switched to fingolimod due to adverse effects or patient desire and the group that switched due to first-line DMT ineffectiveness.

In May 2018, the FDA expanded fingolimod’s indication to include the treatment of children and adolescents aged 10 years and older with relapsing MS, making the immunomodulating drug the first agent specifically approved to treat MS in pediatric patients.² The approval was based on the phase 3 PARADIGMS study, in which fingolimod demonstrated a significant improvement in the primary end point of annualized relapse rate (ARR) compared with interferon beta-1a. Thought leaders Lauren Krupp, MD, and Tanuja Chitnis, MD, recently sat down as part of a NeurologyLive Insights series to discuss the results of that trial, as well as the safety and efficacy of fingolimod in pediatric patients. Watch their commentary below.

REFERENCES

1. Ozakbas S, Cinar BP, Yigit P, Baba C, Sagici O. Five-year real-world data on fingolimod treatment’s effects on cognitive function. Mult Scler Relat Disord. Published online June 22, 2021. doi: 10.1016/j.msard.2021.103089

2. FDA expands approval of Gilenya to treat multiple sclerosis in pediatric patients. News release. May 11, 2018. Accessed August 24, 2021. https://www.fda.gov/news-events/press-announcements/fda-expands-approval-gilenya-treat-multiple-sclerosis-pediatric-patients#:~:text=The%20U.S.%20Food%20and%20Drug,treat%20MS%20in%20pediatric%20patients.