Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis

Nuria Cerdá-Fuertes; Sara Nagy; Sabine Schaedelin; Tim Sinnecker; Esther Ruberte; Athina Papadopoulou; Jens Würfel; Jens Kuhle; Özgür Yaldizli; Ludwig Kappos; Tobias Derfuss; Bernhard F Décard

doi:10.1177/17562864221150312

Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis

Ther Adv Neurol Disord. 2023 Feb 6:16:17562864221150312. doi: 10.1177/17562864221150312. eCollection 2023.

Authors

Nuria Cerdá-Fuertes^{1

2}, Sara Nagy¹, Sabine Schaedelin^{3

4}, Tim Sinnecker^{1

5}, Esther Ruberte^{5

2}, Athina Papadopoulou^{1

2}, Jens Würfel⁵, Jens Kuhle^{1

3}, Özgür Yaldizli^{1

2}, Ludwig Kappos^{1

3}, Tobias Derfuss^{1

3}, Bernhard F Décard¹

Affiliations

¹ Neurology Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
² Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
³ Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Clinical Trial Unit, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Medical Image Analysis Center (MIAC AG), Basel and qbig, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.

Abstract

Background: Clinical and radiological signs of recurring disease activity (RDA) have been described in patients with multiple sclerosis (pwMS) after discontinuation of fingolimod (FGL).

Objective: To describe frequency, severity and potential risk factors for RDA after FGL discontinuation in a large real-world cohort of pwMS.

Methods: Post-FGL RDA was defined as evidence of clinical and/or radiological activity within 6 months after FGL discontinuation. Relapses with Expanded Disability Status Scale increase ⩾2 points and/or magnetic resonance imaging (MRI) activity with at least five cerebral gadolinium-enhancing lesions and/or ⩾6 cerebral new T2 lesions were defined as severe recurring disease activity (sRDA). Using a multivariate logistic model, we explored the influence of age, disease duration, sex, clinical, and MRI activity under FGL on the occurrence of RDA.

Results: We identified 110 pwMS who discontinued FGL. Thirty-seven (33.6%) developed post-FGL RDA and 13 (11.8%) also fulfilled criteria for sRDA. Younger age at diagnosis [odds ratio (OR) = 1.10, p < 0.01], shorter disease duration (OR = 1.17, p < 0.01), and MRI activity under FGL (OR = 2.92, p = 0.046) were independent risk factors for the occurrence of post-FGL RDA.

Conclusion: Individual risk assessment and optimal treatment sequencing can help to minimize the risk of post-FGL RDA. Early switch to highly effective disease-modifying therapy might reduce occurrence of post-FGL RDA.

Keywords: discontinuation; disease activity; fingolimod; multiple sclerosis; rebound; switch.