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Clinical effectiveness of reduced fingolimod dose in relapsing remitting multiple sclerosis—a Portuguese cohort

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Abstract

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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Abbreviations

AE:

Adverse events

ALT:

Alanine aminotransferase

ARR:

Annualized relapse rate

AST:

Aspartate aminotransferase

CNS:

Central nervous system

DMT:

Disease-modifying therapy

EDSS:

Expanded disability status scale

FTY:

Fingolimod

FTY-ED:

Fingolimod-everyday

FTY-ND:

Fingolimod-nondaily

MS:

Multiple sclerosis

RRMS:

Relapsing remitting multiple sclerosis

SD:

Standard deviation

ULN:

Upper limit of normal

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Authors and Affiliations

  1. Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Praceta Professor Mota Pinto, 3000-075, Coimbra, Portugal

    Joana Ramos-Lopes, Sónia Batista, Inês Correia, Carla Nunes, Carmo Macário & Lívia Sousa

  2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Sónia Batista, Inês Correia & Lívia Sousa

  3. Neuroradiology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

    Pedro Barradas

  4. Pharmaceutical Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

    Isabel Campelo

Authors
  1. Joana Ramos-Lopes
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  2. Sónia Batista
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  3. Pedro Barradas
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  4. Isabel Campelo
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  5. Inês Correia
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  6. Carla Nunes
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  7. Carmo Macário
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  8. Lívia Sousa
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Corresponding author

Correspondence to Joana Ramos-Lopes.

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Conflict of interest

Joana Ramos-Lopes has nothing to disclose.

Sónia Batista has received grant support from Biogen and speakers’ bureau fees from Biogen, Novartis, Merck, Roche, and Sanofi-Genzyme.

Inês Correia has received speakers’ bureau fees from Biogen, Novartis, Merck, Roche, Teva, and Sanofi-Genzyme.

Carla Nunes, Carmo Macário, and Lívia Sousa have received speakers’ bureau fees from Biogen, Novartis, Merck, Roche, Teva, Bayer, and Sanofi-Genzyme.

Ethical approval

The study was approved by the local Ethics Committee.

Research involving human participants

None.

Informed consent

Informed consent to patients was dispensed by the local Ethics Committee given the retrospective and merely observational nature of the study.

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Ramos-Lopes, J., Batista, S., Barradas, P. et al. Clinical effectiveness of reduced fingolimod dose in relapsing remitting multiple sclerosis—a Portuguese cohort. Neurol Sci 42, 1039–1043 (2021). https://doi.org/10.1007/s10072-020-04629-6

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  • DOI: https://doi.org/10.1007/s10072-020-04629-6

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