NATIONAL HARBOR, MD—After eight years of fingolimod treatment, disability improves or remains stable for a majority of patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2016 CMSC Annual Meeting.
The two-year phase III FREEDOMS and FREEDOMS II trial data revealed that fingolimod reduced confirmed disability progression in patients with MS, but evaluating disability over a longer time span may help to determine the full impact of treatment. Shannon Ritter, MD, an employee of Novartis Pharmaceuticals, and her colleagues examined trends in changes in Expanded Disability Status Scale (EDSS) scores over a maximum of eight years. Their objective was to investigate patients’ evolving disability patterns and the impact of fingolimod treatment on long-term disability.
The investigators conducted post hoc analyses that included data collected for as long as 96 months from baseline from patients randomized to fingolimod 0.5 mg or placebo in both two- year FREEDOMS trials. In addition, patients who switched or continued 0.5 mg fingolimod in the extension trials, and those who continuously received 0.5 mg fingolimod in the LONGTERMS trial, were also included in the analysis.
Disability progression was considered minimal if there was an increase or decrease of 0.5 points from a baseline EDSS score of 5.5 or lower, or if there was no change in a baseline score greater than 5.5. Disability was considered to have improved if the baseline EDSS score decreased by 1.0 or more points, either confirmed at six months only, or confirmed at six months and sustained until month 24, 48, or 96. Worsening was defined as an increase of 1.0 point or more from the baseline EDSS score, either confirmed at six months only or confirmed at six months and sustained until month 24, 48, and 96. Stable/improving was defined as the minimal and improving categories combined, and fluctuating was identified as changes in the EDSS score that were different from those defined in other categories.
Results showed that significant improvements were more likely to be noted after longer periods of continuous fingolimod treatment. Disability fluctuated or changed minimally at 24 months, and the proportion of patients in these categories decreased by almost 50% at 96 months. Researchers noted that 22.6% of patients in the continuous fingolimod group were improving, 22.6% were worsening, and 54.7% of patients had minimal change or were fluctuating at 96 months. However, 20% of patients in the switch group were improving, 28% were worsening, and 52% had changed minimally or were fluctuating at 96 months. Overall, the proportion of patients improving or worsening was larger at 96 months than at 24 months.
Researchers also investigated the impact of delaying fingolimod treatment on long-term disability and concluded that patients with worsening disability over 96 months benefited from early fingolimod treatment. Fewer patients in the continuous fingolimod group had worsening disability, compared with the switch group, at 24 months. By 96 months, the continuous fingolimod group maintained proportionally fewer patients with worsening disability, compared with the switch group. The data indicate that the majority of patients receiving continuous fingolimod treatment were either stable or improving at 96 months. Proportionally more patients had improving disability at 96 months, compared to 24 months. These results support the practice of longer follow-up periods to properly detect the impact of treatment.
This study was supported by Oxford PharmaGenesis in Oxford UK, and funded by Novartis Pharmaceuticals.
—Erica Robinson