Research questions: Can we safely discontinue first line medication in long-term stable relapsing remitting multiple sclerosis (RRMS)? Does this affect quality of life and cost-effectiveness of treatment in MS?
Hypothesis: Discontinuation of treatment is safe, cost-effective and increases quality of life by reducing exposure to unnecessary treatment
Study design: National multicenter rater-blinded randomized and controlled clinical trial (RCT)
Study population: RRMS patients on first-line therapy, with no signs of inflammation for 5 previous years; no relapses or no new or contrast-enhancing brain MRI lesions showing focal inflammation.
Intervention: 1:1 randomisation in a “discontinuation” or “continuation of treatment” group who either discontinues or continues their own treatment after inclusion.
Outcome measures: The primary end-point is the proportion of patients who shown no signs of inflammation after 2 years. Secondary end-points are amongst others disability progression, relapses, brain MRI lesions, quality of life measurements and biomarker levels.
Sample size and data-analysis: The estimated sample size is 130 based on an estimated 97,5% stability in the continuation group and 90% stability in the discontinuation-group and 20% missing data over the follow-up period. For the primary endpoint, the return of inflammatory disease activity after 2 years, a 2x2 contingency table will be used to estimate the risk difference for the return of inflammatory disease activity after 2 years (yes/no) between the two groups. If the lower bound of the corresponding 95% confidence interval is not bigger than 7,5% we conclude non-inferiority of discontinuing medication. Furthermore, a survival analysis (with an intention-to-treat approach) regarding the time to return of inflammatory activity will be included. Regression models will be used for analysis on the secondary endpoints.