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A Prospective, Observational Study Assessing Effectiveness, Safety, and QoL of Greek Patients with Multiple Sclerosis Under Treatment with Fingolimod

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Abstract

Introduction

Fingolimod is the first approved oral therapy for relapsing–remitting multiple sclerosis (RRMS). The present study aimed to further characterize fingolimod’s safety profile, and to assess the patient-reported treatment satisfaction and impact of fingolimod on the quality of life (QoL) of patients with multiple sclerosis (MS) treated in routine care in Greece.

Methods

This was a multicenter, prospective, observational, 24-month study conducted in Greece by hospital-based and private practice neurologists who specialize in MS. Eligible patients had initiated fingolimod within 15 days in accordance with the locally approved label. Safety outcomes included any adverse event (AE) observed during the study period and efficacy outcomes included both objective (disability progression and 2-year annualized relapse rate) and patient-reported assessments (Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 and the EuroQol (EQ)-5-dimension (5D) 3-level instruments).

Results

A total of 489 eligible patients (age 41.2 ± 9.8 years; 63.7% female; 4.2% treatment-naive) were exposed to fingolimod for a median of 23.7 months. During the observation period, 20.5% of the participants experienced 233 AEs. Lymphopenia (8.8%), leukopenia (4.2%), hepatic enzyme increased (3.4%), and infections (3.0%) were the most common. Most patients (89.3%) did not experience disability progression; the 2-year annualized relapse rate decreased by 94.7% compared to baseline. The median EQ-visual analogue scale (VAS) was 74.5 at month 24 vs. 65.0 at enrollment (p < 0.001) and the EQ-5D index score was 0.80 vs. 0.78, respectively. Significant improvements were noted in the TSQM global satisfaction and effectiveness domain scores between 6 and 24 months post enrollment (median scores at month 24, 71.4 and 66.7, respectively) (p < 0.001). Significant increases from enrollment to the 24th month were also noted in the patients’ global satisfaction and effectiveness domain scores [mean change of 7.4 ± 17.7 (p = 0.005) and mean increase of 5.4 ± 16.2) (p = 0.043), respectively].

Conclusion

In the real-world setting of Greece, fingolimod demonstrates a clinical benefit and a predictable and manageable safety profile, which contribute towards high patient-reported treatment satisfaction and improvements in the QoL of patients with MS.

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Acknowledgements

The authors would like to thank all participants of this study.

Funding

The study was sponsored and funded by Novartis Hellas. Novartis Hellas also funded the journal’s Rapid Service Fee.

Medical Writing, Editorial, and Other Assistance

Editorial assistance in the preparation of this article was provided by Qualitis Ltd. The authors would also like to thank Krinio Palli from Qualitis Ltd for medical writing support funded by Novartis Hellas.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Dimos D Mitsikostas, Anastasios Orologas, Efthimios Dardiotis. Nikolaos Fakas, Triantafyllos Doskas, Klimentini Karageorgiou, Maria Maltezou, Ioannis Iliopoulos, Michail Vikelis and Nikolaos Grigoriadis all contributed to the study conception and design, as well as the collection, analysis, and interpretation of data. The first draft of the manuscript was written by Qualitis Ltd and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Prior Presentation

Results of this study have been presented in part in the 2017 ECTRIMS Congress. Mitsikostas DD et al. Patient satisfaction and quality of life during treatment with fingolimod in multiple sclerosis: Results from the ‘DIAMOND’ non-interventional, prospective, observational study in Greece. Poster P825, presented at the 7th Joint Congress of the European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis, October 25–28, 2017, Paris, France. Mitsikostas DD et al. Long-term safety profile of fingolimod in the treatment of multiple sclerosis: Results of the ‘DIAMOND’ non-interventional, prospective, observational study conducted in the routine care of Greece. Poster EP1697, presented at the 7th Joint Congress of the European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis, October 25–28, 2017, Paris, France. Mitsikostas DD et al. Long-term effectiveness of fingolimod in multiple sclerosis patients treated in the routine care of Greece: Results of the ‘DIAMOND’ non-interventional, prospective, observational study. Poster EP1709, presented at the 7th Joint Congress of the European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis, October 25–28, 2017, Paris, France.

Disclosures

Dimos D Mitsikostas (current affiliation 1st Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece) received grants from Biogen, Genzyme, Merz, ElectroCore; consulting fees or honoraria from Allergan, Amgen, Novartis, Roche, Teva and Mylan; travel support from Allergan, Amgen, Cefaly and Genesis Pharma; fees for participation in review activities from Novartis, Eli Lily, Amgen, Genesis Pharma and Teva; speaker’s fees from Eli Lily, Novartis, Merck-Serono, Teva and Roche; Anastasios Orologas (current affiliation Multiple Sclerosis Center, Saint Luke's Hospital, Thessaloniki, Greece) received travel grants and/or speaking honoraria and consultation fees from Merck, Bayer Schering, Sanofi-Genzyme, Teva Pharmaceuticals, Novartis, Genesis Pharma, Mylan, Viatris, Lundbeck and Roche; received research grant support from Merck, Sanofi-Genzyme, Teva Pharmaceuticals, Novartis, Genesis Pharma, AB Science, Mylan; Efthimios Dardiotis received grants, consulting fees and travel support from Bayer, Novartis, Genesis Pharma, Sanofi-Genzyme, Merck-Serono, Roche, Teva, Elpen, Abbvie, Allergan, Ipsen and UCB; Nikolaos Fakas has received grants from Roche Diagnostics Ltd; compensation for consultation, speech honoraria and travel support from Novartis, Genzyme, Teva, Merck, Biogen, Celgene, Roche, Sanofi, Actelion and Receptos; Triantafyllos Doskas (current affiliation Department of Neurology, Athens Naval Hospital, Athens, Greece) received travel grants and/or speaking honoraria and consultation fees from Novartis, Genesis, Biogen, Teva Pharmaceuticals, Specifar, Bayer Schering, Sanofi-Genzyme, Mylan, Viatris, Lundbeck, Roche, Allergan, and Merck Serono; Klimentini Karageorgiou (current affiliation Neurology Department, Athens Medical Centre, Athens, Greece) received travel grants and/or speaking honoraria and consultation fees from Novartis, Genesis, Biogen, Teva Pharmaceuticals, Specifar and Sanofi; Maria Maltezou has no conflict of interest to declare; Ioannis Iliopoulos consulting fees or honoraria and research grant support from Merck, Sanofi-Genzyme, Teva Pharmaceuticals, Novartis; Michail Vikelis (current affiliation Mediterraneo Hospital, Glyfada, Greece and Glyfada Headache Clinic, Glyfada, Greece) received investigator fees and/or advisory board member and/or consultancy and/or travel grants from Amgen, Allergan, Brain Therapeutics, Novartis, and Lundbeck. He is a former employee of Novartis Hellas SACI; Nikolaos Grigoriadis received Honoraria and travel support from Biogen Idec, Biologix, Novartis, Teva, Bayer, Merck Serono, Genesis Pharma, Sanofi-Genzyme, Roche; Consultancy fees from Biogen Idec, Novartis, Teva, Bayer, Merck Serono, Genesis Pharma, Sanofi-Genzyme, Celgene, Elpen, Roche; Lecture fees from Biogen Idec, Novartis, Teva, Bayer, Merck Serono, Genesis Pharma, Sanofi-Genzyme, Roche and Research grants from Biogen Idec, Novartis, Teva, Merck Serono, Genesis Pharma, Sanofi-Genzyme, Roche.

Compliance with Ethics Guidelines

The study was performed in accordance with the 1964 Declaration of Helsinki, and its later amendments, the guidelines of Good Pharmacoepidemiology Practice of the International Society of Pharmacoepidemiology, and all applicable local rules and regulations. The study protocol and the informed consent form were approved by the IRBs of all participating hospital sites before enrollment of any patient into the study and performance of study-related procedures. Private practice investigators obtained approval for participation in the study from an IRB of a participating hospital site. A full list of investigator names and individual IRB information can be found in Supplementary Material. All subjects provided written informed consent for their participation in this study.

Data Availability

The authors declare that all relevant data supporting the findings of this study are available within the article.

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Authors and Affiliations

  1. Department of Neurology, Athens Naval Hospital, Athens, Greece

    Dimos D. Mitsikostas

  2. A’ Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece

    Anastasios Orologas

  3. Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, Greece

    Efthimios Dardiotis

  4. Neurology Department, General Military Hospital of Athens, 401, Athens, Greece

    Nikolaos Fakas

  5. Ntoskas K. Triantafillos Private Practice, K. Papakonstantinou 4, Paiania, 19002, Athens, Greece

    Triantafyllos Doskas

  6. The Neurological Institute of Athens, 51, Leof. Vasilissis Sofias Ave, 10676, Athens, Greece

    Klimentini Karageorgiou

  7. Department of Neurology, General Oncology Hospital of Kifissia “Agioi Anargiroi”, Athens, Greece

    Maria Maltezou

  8. Department of Neurology, University Hospital of Alexandroupolis, Alexandroupolis, Greece

    Ioannis Iliopoulos

  9. Novartis Hellas SACI, Athens, Greece

    Michail Vikelis

  10. B’ Department of Neurology, School of Medicine, Faculty of Health Sciences, Multiple Sclerosis Center, Aristotle University of Thessaloniki, AHEPA University Hospital, Kiriakidi 1, 54621, Thessaloniki, Greece

    Nikolaos Grigoriadis

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Mitsikostas, D.D., Orologas, A., Dardiotis, E. et al. A Prospective, Observational Study Assessing Effectiveness, Safety, and QoL of Greek Patients with Multiple Sclerosis Under Treatment with Fingolimod. Adv Ther 40, 2217–2233 (2023). https://doi.org/10.1007/s12325-022-02388-8

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