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With a growing number of disease-modifying therapies becoming available for relapsing multiple sclerosis, there is an important need to gather real-world evidence data regarding long-term treatment effectiveness and safety in unselected patient populations. Although not providing as high a level of evidence as randomized controlled trials, and prone to bias, real-world studies from observational studies or registries nevertheless provide crucial information on real-world outcomes of a given therapy. In addition, evaluation of treatment satisfaction and impact on quality of life are increasingly regarded as complementary outcome measures. Fingolimod was the first oral disease-modifying therapy approved for relapsing multiple sclerosis. This review aims to summarize current knowledge on the long-term effectiveness and safety outcomes of multiple sclerosis patients on fingolimod. Impact on treatment satisfaction and quality of life will be discussed according to available data.

Background and purpose Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (FLAIR-rSI) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial, intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of DWI-FLAIR mismatch, i.e., in those with no marked FLAIR hyperintensity in the region of the acute DWI lesion. In this post-hoc analysis, we investigated if quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analysed by binary logistic regression using different endpoints, i.e., favourable outcome defined as mRS 0-1, independent outcome defined as mRS 0-2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for NIHSS at symptom onset and stroke lesion volume. Results FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS 0-1 (p=0.169) and shift analysis (p=0.086), but 2 reached significance for mRS 0-2 (p=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical endpoints with increasing FLAIR-rSI. Conclusion In patients in whom no marked parenchymal FLAIR hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of DWI lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

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