Assessing the duration of EDSS improvement after a therapy start: A novel approach applied to the long-term extension of the PRISMS study

Background: In a chronic and progressive disease such as multiple sclerosis (MS), the improvement on Expanded Disability Status Scale (EDSS) can be a transient event. Therefore, estimating the prevalence of disability improvement over time, accounting both for improvement incidence and duration, is of interest. The aim of this study was to show the application of a simple estimator for the proportion of patients with sustained improvement over time using data from the long-term extension of the PRISMS trial.Methods: A total of 534 relapsing-remitting MS (RRMS) patients from the PRISMS trial were included. Patients with a baseline EDSS of 0 were excluded. Patients were randomized to placebo (n = 178), subcutaneous interferon beta-1a (sc IFN beta-1a) 22 mu g (n = 181) or sc IFN beta-1a 44 mu g (n = 175). At Year 2, patients receiving placebo were re-randomized to sc IFN beta-1a 22 mu g or 44 mu g (delayed sc IFN beta-1a) while patients receiving sc IFN beta-1a 22 mu g or 44 mu g continued their initial regimen. Patients were followed up for over 7 years post-randomization. Disability improvement was defined as a 1-point decrease in EDSS from baseline confirmed at 6 months. Prevalence of improvement was estimated as difference of Kaplan-Meier (KM) estimators while the cumulative incidence of improvement was calculated using the standard KM curves.Results: No significant differences in cumulative incidence of EDSS improvement at 3 years between delayed sc IFN beta-1a (20.3%) and sc IFN beta-1a 22 mu g (20.8%; p = 0.49) or 44 mu g (21.3%; p = 0.33). When taking duration of improvement into account, the proportion of patients showing an improved condition after 3 years was 10.1% with delayed sc IFN beta-1a, 11.3% with sc IFN beta-1a 22 mu g (p = 0.17) and 15.4% with sc IFN beta-1a 44 mu g (p = 0.037) that was substantially maintained over the long term.Conclusions: With the use of this new statistical methodology, it is possible to estimate the time to improvement as well as the duration of improvement, information that is better suited to describing a non-final outcome like disability improvement. In this case, early sc IFN beta-1a 44 mu g initiation had a greater proportion of patients with a sustained disability improvement over a long period of follow-up as compared to patients who had initially been randomized to placebo. In contrast, no significant differences on the cumulative incidence of improvement were observed.

Automated summary

This study aimed to estimate the proportion of patients with sustained disability improvement over time using data from the long-term extension of the PRISMS trial in MS. The use of new statistical methodology is helpful in describing non-final outcomes like disability improvement.