Overdosing, does this happen with fingolimod?

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Overdosing is a current theme in MS treatment and in the era of COVID-19 attention has focus on whether extended dosing intervals could be used. Fingolimod is a once a day treatment but it has a long half-life of about 6-9 days meaning that it take 6-9 days for half the drug to disappear. So do you need to treat every day, it looks like the answer is no, but as ever we need a study .

Clinical effectiveness of reduced fingolimod dose in relapsing remitting multiple sclerosis-a Portuguese cohort.Ramos-Lopes J, Batista S, Barradas P, Campelo I, Correia I, Nunes C, Macário C, Sousa L.Neurol Sci. 2020 Jul 28. doi: 10.1007/s10072-020-04629-6. Online ahead of print.

Background: Fingolimod is an oral daily treatment for relapsing remitting multiple sclerosis (RRMS). A decrease in lymphocytes count is a common side effect, whereby clinicians occasionally propose a reduced dose rather than its discontinuation. However, current data on the effectiveness of these regimens are scarce and contradictory. Our objective was to investigate if the fingolimod effectiveness is maintained with reduction in dosing frequency.

Methods: Retrospective and observational study of RRMS patients taking fingolimod-nondaily (FTY-ND) for at least 6 months. Propensity score-based matching was performed to select patients taking daily dose (FTY-ED) with comparable baseline characteristics: age, sex, disease duration, annualized relapse rate (ARR), and expanded disability status scale (EDSS). Afterwards, clinical and laboratorial assessment was evaluated in both groups.

Results: Thirty-six patients were included in each group (FTY-ED vs. FTY-ND). Decrease in lymphocytes count was the main reason for switching to FTY-ND (88.9%). Previous treatment with natalizumab was inversely associated with risk of reducing dose (OR 0.253, 95%CI = 0.08-0.807, p = 0.016). There were no significant differences in clinical disease activity between patients FTY-ED vs. FTY-ND: mean ARR 0.4 vs. 0.3 (p = 0.247), median EDSS 2.0 vs. 2.0 (p = 0.687), and proportion of patients with EDSS increase 8.3% vs. 13.9% (p = 0.453). FTY-ND was overall well tolerated and was associated with an increase in the mean lymphocytes count (362 ± 103 cells/mm3 to 541 ± 183 cells/mm3, p < 0.001).

Conclusion: These data suggest that the effectiveness of FTY is maintained despite the reduction of the dose, minimizing the most common adverse events. These findings warrant further confirmation, ideally with randomized clinical trials.

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6 comments

  • Interesting and relevant but how likely is the necessary clinical trial in the current climate? And would a reduced dose reduce the blunting effect on a covid vaccine?

  • “Previous treatment with natalizumab was inversely associated with risk of reducing dose“……I found this to be an interesting finding of the study.

    It seems these drugs behave differently when used after treatment with a heavy hitting DMT. I wish there were more studies investigating the relationship, and possible benefits, of using lower efficacy drugs after B or T cell depletion.

  • This is single case report not evidence but I have been on alternate day fingo since 2015 in response to lymphopaenia which at times is below 200. The only trouble i have had was small intranucleatr ophthalmoplegia when held for 10 days to try and get lymphocytes above 200 (I used to fiddle with dosing interval and vary every 3rd or 4th day even based on wcc but dont bother anymore)

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