Gilenya’s Optimal Dose for RRMS Confirmed in Review of Clinical Trials

Gilenya (fingolimod) at its approved 0.5 mg daily dose continues to be the optimal dose for people with relapsing-remitting MS (RRMS), a systematic review of 11 clinical trials confirmed.

A 0.25 mg/day dose, however, also showed improvement over placebo in MRI outcomes and patient satisfaction, the researchers noted, and further studies are warranted to better evaluate Gilenya at this lower daily dose.

The review study, “Different Doses of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,” was published in the journal Frontiers in Pharmacology.

Gilenya, an oral therapy developed by Novartis, is approved to treat RRMS, the disease’s most common form, and other relapsing forms of MS.

It works to retain immune cells within lymph nodes, preventing them from reaching the brain and spinal cord. This reduces the inflammation and damage to the myelin sheath — the fatty coating on nerve fibers — which is the underlying cause of MS.

Several clinical trials established the safety and efficacy of Gilenya. However, there are fewer comparisons evaluating its effects at different doses. The approved and most widely used dose is 0.5 mg per day, but whether a lower dose can maintain effectiveness while reducing side effects is unclear.

Investigators based at the First Affiliated Hospital of Soochow University, in China, pooled data from previous clinical trials to conduct a large-scale (meta) analysis to determine the safety and efficacy of Gilenya at different doses.

“The objective of this systematic review was to evaluate the efficacy and safety of the four existing doses of [Gilenya] in the treatment of RRMS, especially the dose of 0.5 [mg/day],” the team wrote.

Researchers searched medical databases for published studies that included adults diagnosed with RRMS (ages 18 to 65) who participated in randomized controlled trials — studies in which patients were randomly assigned to Gilenya or a control, such as a placebo or another disease-modifying therapy.

Along with safety, included studies contained data on clinical outcomes, such as the annualized relapse rate (ARR), the number of participants free of relapse, expanded disability status scale (EDSS) scores, as well as MRI scans and self-report outcomes.

The final selection included 7,182 patients who took part in 11 Phase 2, Phase 3, and Phase 4 clinical trials, all conducted by Novartis.

Combined analysis revealed that, compared with controls, patients given 0.5 mg/day of Gilenya had a significantly lower ARR, with a mean difference of 0.17 fewer relapses per year. In addition, these patients also had less disability progression — as determined by a 0.09 lesser change in EDSS scores — than those in the control group.

The higher dose of the 1.25 mg/day group also showed significantly better outcomes than the control group, with a 0.24 lower rate of relapses per year and a 0.14 drop in EDSS scores.

Significant differences were also seen in the number of participants free of relapse between controls and those on three different Gilenya doses (5.0, 1.25, and 0.5 mg/day). But patients who received a lower treatment dose (0.25 mg/day) did not show significant differences with controls in the rate of relapses and the number of participants free of relapse.

Compared with controls, all Gilenya dose groups (5.0, 1.25, 0.5, and 0.25 mg/day) prevented the formation of gadolinium-enhanced T1 lesions on MRI scans — a marker of active MS lesions that correlates with inflammation.

The number of people with no new or newly enlarged lesions was also significantly smaller at all doses relative to controls, as measured by T2 scans. These scans are used to detect areas of myelin damage.

Additionally, at 0.5 and 1.25 mg/day, Gilenya resulted in significantly less brain atrophy (shrinkage). No changes were seen at the lower dose of 0.25 mg/day.

Patient-reported outcomes showed lower depression scores in those given the 0.5 mg/day dose relative to controls, as measured by the Beck depression inventory (BDI). Patients at this dose also expressed greater treatment satisfaction, with a reported mean increase of 13.03 in the treatment satisfaction questionnaire for medication (TSQM) score compared with controls.

Reported TSQM scores were also significantly among patients treated at the lower 0.25 mg/day dose. Scores for BDI at this dose were not included in this study.

Safety outcomes assessed by the combined data found Gilenya at its highest dose of 5.0 mg/day also carried the highest risk of adverse events. There was also a significantly higher risk of serious adverse events at 0.5 mg/day than was seen in controls.

Further analysis of different types of serious adverse events from two clinical trials found an increased risk at 0.5 mg/day for basal-cell carcinoma — the most common form of skin cancer. This risk was a major contributor to the calculation for all serious adverse events.

“In conclusion, the present study indicated that combined safety and the efficacy comprehensively obtained from clinical outcomes, MRI outcomes and patients evaluated outcomes, 0.5 [mg/day] remains to be the optimal dose of [Gilenya] for RRMS patients so far,” the scientists wrote.