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. 2022 Feb 24;4(1):e000215.
doi: 10.1136/bmjno-2021-000215. eCollection 2022.

Effect of fingolimod on health-related quality of life in paediatric patients with multiple sclerosis: results from the phase 3 PARADIG MS Study

Lauren Krupp  1 , Brenda Banwell  2 , Tanuja Chitnis  3 , Kumaran Deiva  4 , Jutta Gaertner  5 , Angelo Ghezzi  6 , Peter Huppke  5   7 , Emmanuelle Waubant  8 , Virginia DeLasHeras  9 , Amin Azmon  10 , Rajesh Karan  11
Affiliations

Effect of fingolimod on health-related quality of life in paediatric patients with multiple sclerosis: results from the phase 3 PARADIG MS Study

Lauren Krupp et al. BMJ Neurol Open. .

Abstract

Background: In the PARADIGMS Study, fingolimod demonstrated superior efficacy versus interferon (IFN) β-1a and comparable overall incidence of adverse events but slightly higher rate of serious adverse events in patients with paediatric-onset multiple sclerosis (PoMS). Here, we report the health-related quality of life (HRQoL) outcomes from PARADIGMS.

Methods: Patients with PoMS (N=215; aged 10-<18 years) were randomised to once-daily oral fingolimod (N=107) or once-weekly intramuscular IFN β-1a (N=108). HRQoL outcomes were assessed using the 23-item Pediatric Quality of Life (PedsQL) scale that comprises Physical and Psychosocial Health Summary Scores (including Emotional, Social and School Functioning). A post hoc inferential analysis evaluated changes in self-reported or parent-reported PedsQL scores from baseline up to 2 years between treatment groups using an analysis of covariance model.

Results: Treatment with fingolimod showed improvements versus IFN β-1a on the PedsQL scale in both the self-reported and parent-reported Total Scale Scores (4.66 vs -1.16, p≤0.001 and 2.71 vs -1.02, p≤0.05, respectively). The proportion of patients achieving a clinically meaningful improvement in the PedsQL Total Scale Score was two times higher with fingolimod versus IFN β-1a per the self-reported scores (47.5% vs 24.2%, p=0.001), and fingolimod was favoured versus IFN β-1a per the parent-reported scores (37.8% vs 24.7%, p=non-significant). Group differences in self-reported Total Scale Scores in favour of fingolimod were most pronounced among patients who had ≥2 relapses in the year prior to study entry or who showed improving or stable Expanded Disability Status Scale scores during the study.

Conclusion: Fingolimod improved HRQoL compared with IFN β-1a in patients with PoMS as evidenced by the self-reported and parent-reported PedsQL scores.

Keywords: multiple sclerosis; paediatric neurology; quality of life.

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Conflict of interest statement

Competing interests: LK received personal compensation for activities as a consultant and/or participant on advisory boards for Biogen, Eisai, Gerson Lehrman, Janssen, Medscape, NeuroLive, Novartis, Roche and Sanofi. She has received royalties for the Fatigue Severity Scale from pharmaceutical and biotechnology companies, grant support from the National Multiple Sclerosis Society, and Department of Defense and research support from Novartis, Biogen, Genentech, the Lourie Foundation. She was compensated for her role as a back-up central MRI reviewer for the PARADIGMS Study. BB served as a consultant for Biogen Idec, Novartis, Teva Neuroscience, Merck Serono, Canadian MS Society Scientific Research Foundation, Canadian Multiple Sclerosis Society, National Multiple Sclerosis Society and Canadian Institutes of Health Research. She served as a remunerated central MRI reviewer for the present study. TC received personal compensation for advisory boards/consulting from F Hoffman-La Roche, Biogen and Novartis and financial support for research activities from the National Multiple Sclerosis Society, NIH and Department of Defense, Biogen, Merck Serono, Verily and Novartis. KD received personal compensation for speaker activities from Novartis, Servier, Biogen and Sanofi. JG, in the last 3 years, received honoraria for lectures and consultancy fees from Bayer, Novartis and Sanofi as well as funding for a research project from Novartis. AG received honoraria for speaking from Almirall, Biogen Idec, Merck Serono, Novartis, Genzyme and Sanofi-Aventis and for consultancy from Merck Serono, Biogen Idec, Teva, F Hoffmann-La Roche and Novartis. PH received honoraria for lectures and consultancy fees from Bayer, Merck, Biogen and Novartis. EW is funded by the NIH, NMSS, PCORI and Race to Erase MS. She volunteers on an advisory board for a Novartis trial. She is a site PI for clinical trials with Roche and Novartis. She has received honoraria from MS@TheLimit and The Corpus for educational talks. VD, AA and RK are employees of Novartis.

Figures

Figure 1
Figure 1
Examples of questions from the PedsQL parent-reporting and self-reporting scale. PedsQL, Pediatric Quality of Life.
Figure 2
Figure 2
Scoring procedure for the PedsQL scale. HRQoL, health-related quality of life; PedsQL, Pediatric Quality of Life.
Figure 3
Figure 3
Mean change in total PedsQL scale score at EOS per the self-reports and parent-reports by (A) occurrence of confirmed relapses during the study, (B) number of relapses in the last 2 years prior to study start and (C) EDSS status at EOS. *p≤0.1; **p≤0.05; ***p≤0.01. The p values are from a Wilcoxon rank-sum test and represent the significant effect of fingolimod versus IFN β-1a. BL indicates the mean baseline PedsQL scale score. For patients with a baseline EDSS score of ≤5.0, a decrease of ≤1 point is defined as improvement, a change from –0.5 to 0.5 is defined as stable and an increase of ≥1 point is defined as deterioration; for patients with a baseline EDSS score of >5.0, a decrease of ≤0.5 point is defined as improvement, 0 change is defined as stable and an increase of ≥0.5 point is defined as deterioration. BL, baseline; EDSS, Expanded Disability Status Scale; EOS, end of study; IFN, interferon; n, number of subjects with a value at both baseline and EOS; PedsQL, Pediatric Quality of Life.
Figure 4
Figure 4
LS mean change in the PedsQL scale and subscale scores at EOS per the self-reports and parent-reports. *p≤0.05; **p≤0.01; ***p≤0.001. BL indicates the mean baseline PedsQL scale score. EOS is defined as the last assessment taken on or before the final study phase visit date. LS mean change is obtained from an ANCOVA model adjusted for treatment, pubertal status, sex, number of relapses in the 2 years prior to the study, EDSS at baseline and the baseline value of the respective PedsQL scale. ANCOVA, analysis of covariance; BL, baseline; EDSS, Expanded Disability Status Scale; EOS, end of study; IFN, interferon; LS, least square; n, total number of patients with available results for the corresponding time point or time window and included in the analysis; PedsQL, Pediatric Quality of Life.
Figure 5
Figure 5
Proportion of patients with clinically meaningful improvement in the PedsQL scale scores at EOS per the self-reports and parent-reports. *p≤0.1; **p≤0.05; ***p≤0.01; ****p≤0.001. The p values for the treatment comparison are based on a two-tailed Fisher’s exact test. EOS, end of study; IFN, interferon; N, number of patients with an assessment; n, number of patients with at least a 5-point increase in the score; PedsQL, Pediatric Quality of Life.
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