People with relapsing multiple sclerosis (MS) being treated with Gilenya (fingolimod) for eight or more years show smaller increases in disability over 10 years than those using this treatment for a shorter time, a long-term follow-up study reports.
Longer use of Gilenya also resulted in lesser disability progression, a reduced reliance on walking aids or wheelchairs, and fewer people transitioning to secondary progressive multiple sclerosis (SPMS) over the 10 years of follow-up.
“The ACROSS study: Long-term efficacy of fingolimod in patients with relapsing–remitting multiple sclerosis” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.
The myelin sheath is a fat-rich substance that covers nerve fibers and allows signals relayed by nerve cells to be transmitted very rapidly. In MS patients, however, this protective coat is wrongly targeted and damaged by cells of the immune system. As a result, nerve cells of the central nervous system (the brain and spinal cord) start to die.
Gilenya, an oral treatment, was developed by Novartis to prevent immune cells from leaving lymph nodes and invading the nervous system. It does so by modulating a receptor at the surface of immune cells — the sphingosine 1-phosphate (S1P) receptor — that regulates their exit from lymph nodes.
First approved in 2010, research continues into its use, as long-term outcomes are important in defining whether Gilenya has a sustained effect on disease progression.
In a Novartis-funded study, a research team at the University Hospital Basel and the University of Basel, in Switzerland, examined 10-year follow-up data on 175 patients who were initially enrolled in a six-month, proof-of-concept Phase 2 trial (NCT00333138) testing Gilenya. After finishing their part in this trial, they entered the ACROSS long-term extension study (NCT02307838).
Patients here were evaluated in two groups: those given Gilenya for eight or more years (high exposure group), and those who had received the therapy for fewer than eight years (low exposure group).
Researchers’ primary goal was to compare differences between these two groups regarding disability progression. Other measures of disability, numbers transitioning to progressive MS, and progression of brain lesions were evaluated as secondary measures.
Overall, 104 relapsing MS patients were in the high exposure group, treated with Gilenya for an average of 4,003 days (almost 11 years). The 71 patients in the low exposure group were treated for an average of 1,190 days (about 3.3 years).
Disability scores across the entire population — measured with the Expanded Disability Status Scale (EDSS) — rose by about 0.83 points from baseline (starting measures) to 10 years (of note, higher EDSS scores mark greater disability), results showed. But the increase in disability was lower among those receiving Gilenya for longer periods (mean of 0.58 points), compared with patients in the low exposure group (mean of 1.17 points).
Over these 10 years, fewer high exposure patients experienced disability progression — 34.7% versus 56.1% in the low exposure group. Patients on Gilenya for an average of 3.3 years also needed walking aids earlier and more frequently than those on Gilenya for an average of almost 11 years.
Findings were similar for wheelchair use, first needed at about 6.2 years by low exposure group patients, and used by 16.9% of these people. In the high exposure group, a first need for a wheelchair was seen around a year later, at about 7.2 years, and required by 4.9% of patients here.
A transition from relapsing disease to SPMS was observed in 26 people, and happened earlier and more frequently in patients on shorter-term Gilenya use — 18.2% in the low exposure group transitioned to SPMS, and 8.1% of those in the high exposure group.
Compared to baseline measures, high exposure patients were stable in their MS Functional Composite score — a composite score of cognitive function, gait, and upper extremity abilities — and showed improved cognitive function domain at 10 years of follow-up, while low exposure patients exhibited a worsening in this domain. No significant differences were seen between groups in gait and upper extremity function.
Brain lesion volume increased in both groups over the 10-year period, the researchers reported, but patients in the high exposure group had a smaller mean increase in lesion volume, and fewer new or enlarging lesions. Areas of active brain inflammation were also smaller in those on long-term treatment, but this difference failed to reach statistical significance.
A statistical analysis assessing Gilenya use as a continuous variable showed that the longer the treatment, the longer time they could go without needing an ambulatory device, and the lower would be their disability score at year 10.
Other factors, like time to first use of a wheelchair or time to being classified as having transitioned to SPMS, were not significantly correlated with duration of Gilenya treatment.
No new safety issues were associated with long-term use of Gilenya.
These findings suggest that Gilenya use continues to bring benefits to patients over time, particularly if the therapy is taken for extended periods. But, the researchers noted, it “would certainly be worthwhile to compare the high exposure population with a … real-world population to distinguish the treatment effects from a potential selection bias.”
Nonetheless, they emphasized that “the high persistence rate among patients willing to undergo another assessment 10 years or more after the start of the initial Phase 2 study indicates patients and prescribers perceive fingolimod to be an effective, safe, and well-tolerated treatment.”
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