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. 2023 Dec;29(14):1808-1818.
doi: 10.1177/13524585231205962. Epub 2023 Nov 18.

Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study

Bruno Brochet  1 , Alessandra Solari  2 , Jeannette Lechner-Scott  3 , Fredrik Piehl  4 , Dawn Langdon  5 , Raymond Hupperts  6 , Krzysztof Selmaj  7 , Francesco Patti  8 , Luis Brieva  9 , Eva Maria Maida  10 , Nektaria Alexandri  11 , Andrzej Smyk  11 , Axel Nolting  11 , Birgit Keller  11 , Xavier Montalban  12 , Eva Kubala Havrdova  13
Affiliations

Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study

Bruno Brochet et al. Mult Scler. 2023 Dec.

Abstract

Background: Multiple sclerosis (MS) negatively affects health-related quality of life (HRQoL).

Objective: To evaluate HRQoL in people with highly active relapsing MS treated with cladribine tablets (CladT; 3.5 mg/kg cumulative dose over 2 years) in CLARIFY-MS.

Methods: Changes in the MS quality of life (MSQoL)-54 scores were analysed using a repeated mixed-effects linear model. Subgroup analyses were performed for participants who were pretreatment-naïve and those pretreated with disease-modifying therapies (DMTs) before initiating CladT. Safety and tolerability of CladT were also assessed.

Results: MSQoL-54 physical (mean change = 4.86; 95% confidence interval (CI) = 3.18, 6.53) and mental health (4.80; 95% CI = 3.13, 6.46) composite scores (primary endpoints) showed significant improvement at Month 24 versus Baseline (p < 0.0001). Changes in the MSQoL-54 scores were consistent across the pretreatment-naïve and DMT-pretreated subgroups. No new severe or opportunistic infections occurred. Most post-baseline lymphopenia events were Grade 1-2 in severity. Transient Grade-3 lymphopenia was observed in 19.7% (95/482) of participants. Grade-4 lymphopenia was not observed.

Conclusions: CladT treatment significantly improved the mean MSQoL-54 physical and mental health composite scores over 2 years. CladT efficacy in HRQoL, relapse rates and Expanded Disability Status Scale scores demonstrates its multidimensional effects in MS treatment.

Keywords: CLARIFY-MS; Cladribine tablets; disease-modifying therapies; multiple sclerosis; quality of life.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: B.B. has received consultancy fees, speaker fees, research grants (non-personal) or honoraria from Biogen, Celgene (Bristol Myers Squibb (BMS)), Merck, Novartis, Roche and Sanofi. A.S. has served on advisory boards for Merck, Novartis and Sanofi, and has been invited to speak on behalf of Almirall, Biogen, EXCEMED, Merck and Teva. J.L.-S. has accepted travel compensation from Biogen, Merck and Novartis; her institution receives the honoraria for talks and advisory board commitment, and research grants from Biogen, Celgene (BMS), Merck, Novartis, Roche, Sanofi and Teva. F.P. has received research grants from Janssen, Merck and Sanofi, and fees for serving as a member of the data monitoring committee (DMC) in clinical trials with Lundbeck, Chugai and Roche, and preparation of witness statement for Novartis. D.L. has participated in speaker bureau for Almirall, Bayer, Biogen, BMS, Merck, Novartis, Roche, Sanofi and Teva; has received consultancy fees from Bayer, Biogen, BMS, Merck, Novartis and Teva; and has received research grants from Bayer, Biogen, Merck and Novartis. R.H. has received institutional research grants and fees for lectures and advisory boards from Biogen, Merck and Sanofi. K.S. has received honoraria for speaking, consulting and serving for advisory boards for Biogen, Celgene (BMS), Merck, Novartis, Roche and TG Therapeutics. F.Pa. has served on scientific Advisory Boards for Almirall, Bayer, Biogen, Celgene (BMS), Merck, Novartis, Roche, Sanofi and Teva; he also received speaker honoraria from the same companies and non-personal research grants for his department from Biogen, Merck, Novartis and Sanofi. L.B. has received honoraria, travel expenses, speaker fees and advisory fees from Almirall, Bayer, Celgene (BMS), Biogen, Merck, Novartis, Roche, Sanofi and Teva. E.M.M. has received honoraria for participating as primary investigator in clinical trials from Actelion (Janssen/J&J), Merck, Novartis and Teva. N.A., A.Sm., A.N. and B.K. are employees of Merck Healthcare KGaA, Darmstadt, Germany. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with AbbVie, Actelion, Alexion, Biogen, BMS/Celgene, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, MedDay, Merck, Mylan, NervGen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, EXCEMED, MSIF and NMSS. E.K.H. has received honoraria/research support from Actelion (Janssen/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche, Sanofi and Teva; has served on advisory boards for Actelion (Janssen/J&J), Biogen, Celgene (BMS), Merck, Novartis, Roche and Sanofi; has been supported by the Czech Ministry of Education – project Cooperatio LF1, research area Neuroscience and the project National Institute for Neurological Research (Programme EXCELES, ID project No LX22NPO5107) – funded by the European Union-Next Generation EU.

Figures

Figure 1.
Figure 1.
Participant disposition. AE: adverse event; TS: treated set. aIncludes untreated participants.
Figure 2.
Figure 2.
MSQoL-54 PCS and MCS: change from baseline to the Month 24 according to the subgroups in the TS. CI: confidence interval; DMT: disease-modifying therapy; LS: least squares; MCS: mental health composite score; MSQoL-54: multiple Sclerosis Quality of Life-54 instrument; PCS: physical health composite score; TS: treated set. Error bars indicate CIs.
Figure 3.
Figure 3.
Changes from baseline for each MSQoL-54 scale and composite score for the TS. CI: confidence interval; LS: least squares; MSQoL-54: multiple Sclerosis Quality of Life-54 instrument; TS: treated set. Error bars indicate CIs.
Figure 4.
Figure 4.
Highest post-baseline grade of lymphopenia. DMT: disease-modifying therapy; NCI-CTCAE: National Cancer Institute-Common Criteria for Adverse Events; TS: treated set. Absolute lymphocyte count grading was done based on NCI-CTCAE version 5.0. TS, N = 482; DMT-pretreated, n = 348; pretreatment-naïve, n = 134.
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