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Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration

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Abstract

Background

Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1–2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred.

Objective

To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register.

Methods

The risk of relapses was assessed in relation to different washout durations (< 6, 6–11, 12–17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation.

Results

We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12–17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration.

Conclusion

The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.

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Data availability

The data analyzed in this study are the property of the individual contributing centers. They can be made available upon reasonable request for the purpose of replication of the analyses included in this study and at the discretion of the principal investigators.

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Funding

No funds, grants, or other support was received.

Author information

Authors and Affiliations

  1. Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy

    D. Ferraro, F. Vitetta & P. Sola

  2. Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Via Pietro Giardini 1355, 41126, Modena, Italy

    D. Ferraro

  3. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Policlinico, Bari, Italy

    P. Iaffaldano, T. Guerra, D. Paolicelli & M. Trojano

  4. Department of Neuroscience, Rehabilitation, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy

    M. Inglese & M. Cellerino

  5. Ospedale Policlinico San Martino-IRCCS, Genoa, Italy

    M. Inglese

  6. Regional Referral MS Center, Neurological Unit, University Hospital San Luigi, Orbassano, Italy

    M. Capobianco & S. Malucchi

  7. MS Center-AOU Policlinico Federico II, Naples, Italy

    V. Brescia Morra & E. Pisano

  8. Multiple Sclerosis Center, Gallarate Hospital, ASST Della Valle Olona, Gallarate, Italy

    M. Zaffaroni

  9. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    M. Mirabella

  10. Università Cattolica del Sacro Cuore, Rome, Italy

    M. Mirabella

  11. MS Center, II Division of Neurology, Univ. Della Campania “L. Vanvitelli”, Naples, Italy

    G. Lus

  12. Multiple Sclerosis Centre, AOU Policlinico “G. Rodolico”, Catania, Italy

    F. Patti

  13. Department of Medical and Surgical and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy

    F. Patti

  14. MS Centre, I Division of Neurology, City of Health and Science Turin Univ. Hospital, Turin, Italy

    P. Cavalla

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  1. D. Ferraro
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  2. P. Iaffaldano
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  3. T. Guerra
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Consortia

the Italian MS Register

  • U. Aguglia
  • , M. P. Amato
  • , C. Avolio
  • , R. Balgera
  • , P. Banfi
  • , P. Bellantonio
  • , R. Bergamaschi
  • , D. Cargnelutti
  • , E. Cartechini
  • , L. Chiveri
  • , R. Clerici
  • , E. Cocco
  • , A. Conte
  • , F. Corea
  • , M. C. Danni
  • , G. De Luca
  • , A. Di Sapio
  • , E. Ferraro
  • , S. Galgani
  • , A. Gallo
  • , M. Gatto
  • , P. Gazzola
  • , F. Granella
  • , A. Lugaresi
  • , D. Maimone
  • , G. T. Maniscalco
  • , G. A. Marfia
  • , S. Montepietra
  • , C Paolo
  • , I. Pesci
  • , C. Pozzilli
  • , P. Carlo
  • , A. Protti
  • , R. Quatrale
  • , S. Realmuto
  • , S. Romano
  • , M. Romeo
  • , G. Salemi
  • , S. Leonardo
  • , T. Rocco
  • , V. Paola
  •  & V. Marika

Corresponding author

Correspondence to D. Ferraro.

Ethics declarations

Conflicts of interest

The authors report no conflicts of interest in relation to the contents of this study, but note that patients in the study were treated with a number of disease-modifying drugs and that the authors D.F, P.I, M.I. A.B., V.B.M., M.Z., M.M, G.L., F.P., P.C., M.C., F.V., D.P., P.S., M.T report they have received advisory board membership, speaker honoraria, travel support, research grants, consulting fees or clinical trial support from the manufacturers of these drugs, including Allergan, Almirall, Bayer, Biogen, Bristol Meyers and Squibb, Celgene, CLS Behring, Excemed, FIS, Genzyme, Ipsen, Merck, Novartis, Reload Onlus, Roche, Sanofi, Teva and Ultragenyx.

Ethical approval

Ethical approval was obtained by all participating centers.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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Ferraro, D., Iaffaldano, P., Guerra, T. et al. Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration. J Neurol 269, 1463–1469 (2022). https://doi.org/10.1007/s00415-021-10708-1

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  • DOI: https://doi.org/10.1007/s00415-021-10708-1

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