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. 2024 Jun;271(6):3256-3267.
doi: 10.1007/s00415-024-12270-y. Epub 2024 Mar 5.

Sex impacts treatment decisions in multiple sclerosis

Harald Hegen #  1 , Klaus Berek #  1 , Florian Deisenhammer  1 , Thomas Berger  2   3 , Christian Enzinger  4 , Michael Guger  5   6 , Jörg Kraus  7   8 , Janette Walde  9 , Franziska Di Pauli  10
Affiliations

Sex impacts treatment decisions in multiple sclerosis

Harald Hegen et al. J Neurol. 2024 Jun.

Abstract

Background: Individual disease-modifying treatment (DMT) decisions might differ between female and male people with MS (pwMS).

Objective: To identify sex-related differences in DMT strategies over the past decades in a real-world setting.

Methods: In this cohort study, data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), a nationwide prospectively collected registry mandatory for reimbursement, were retrospectively analyzed. Of 4840 pwMS, those with relapsing-remitting MS, aged at least 18 years, who started DMT and had at least two clinical visits, were identified. At baseline, demographics, Expanded Disability Status Scale (EDSS) score, annualized relapse rate (ARR) in the prior 12 months and MRI lesion load were assessed. At follow-up, ARR, EDSS scores, and DMT were determined.

Results: A total of 4224 pwMS were included into the study and had a median of 10 (IQR 5-18) clinical visits over an observation period of 3.5 (IQR 1.5-6.1) years. Multivariable Cox regression analysis revealed that the probability of DMT escalation due to relapse activity was lower in female than male pwMS (HR 4.1 vs. 8.3 per ARR). Probability of discontinuing moderate-effective DMT was higher in female pwMS when they were younger (HR 1.03 per year), and lower in male pwMS at higher age (HR 0.92). Similarly, female pwMS were more likely to stop highly effective DMT than male pwMS (HR 1.7). Among others, the most frequent reason for DMT discontinuation was family planning in female pwMS. All sex-related effects were independent of disease activity, such as MRI lesion load, baseline ARR or EDSS.

Conclusions: Real-world treatment decisions are influenced by sex-related aspects. Awareness of these associations should prevent unwarranted differences in MS care.

Keywords: Gender; Multiple sclerosis; Registry; Sex; Treatment.

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Conflict of interest statement

HH has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi-Genzyme and Teva. He is associate editor of Frontiers in Neurology. KB has participated in meetings sponsored by, received speaking honoraria or travel funding from Roche, Biogen, Sanofi and Teva. FD has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene-BMS, Genzyme-Sanofi, Horizon, Merck, Novartis Pharma, Roche, and Teva. His institution has received research grants from Biogen and Genzyme Sanofi. He is section editor of the MSARD Journal (Multiple Sclerosis and Related Disorders) and review editor of Frontiers Neurology. TB has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Almirall, Biogen, Bionorica, BMS/Celgene, Eisai, Horizon, Jazz Pharmaceuticals, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sanofi Aventis/Genzyme, Sandoz, TG Therapeutics, TEVA and UCB. His institution has received financial support in the last 2 years by unrestricted research grants (Biogen, BMS/Celgene, Novartis, Sanofi Aventis/Genzyme, Roche, TEVA) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, BMS/Celgene, Merck, Novartis, Roche, Sanofi Aventis/Genzyme, TEVA. CE received funding for travel and speaker honoraria from Biogen, Bayer, Celgene, Merck, Novartis, Roche, Shire, Genzyme, and Teva Pharmaceutical Industries Ltd./sanofi-aventis; re- search support from Merck Serono, Biogen, and Teva Pharmaceutical Industries Ltd./sanofi-aventis; serving on scientific advisory boards for Bayer, Biogen, Celgene, Merck, Novartis, Roche and Teva Pharmaceutical Industries Ltd./sanofi-aventis. MG received support and honoraria for research, consultation, lectures and education from Alexion, Almirall, Bayer, Biogen, Bristol-Myers-Squibb, Celgene, Genzyme, Horizon, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sanofi Aventis and TEVA ratiopharm. JK received consulting and/or research funding and/ or educational support from Almirall, Bayer, Biogen, Celgene/ Bristol Myers Squibb, MedDay, Medtronic, Merck, Novartis, Roche, Sanofi- Aventis, Shire, and TEVA ratiopharm. JW has nothing to disclose. FDP has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Roche and Teva.

Figures

Fig. 1
Fig. 1
Patient selected by various inclusion criteria. ALZ, Alemtuzumab; AMST, Austrian Multiple Sclerosis Treatment; CLA, cladribine; DMF, dimethyl fumarate; DMT, disease-modifying treatment; FTY, fingolimod; FU, follow-up; GLAT, glatiramer acetate; hDMT, high-efficacy DMT; mDMT, moderate-efficacy DMT; IFN, interferon-beta; NTZ, natalizumab; OCR, ocrelizumab; TER, teriflunomide
Fig. 2
Fig. 2
Different DMT in women and men at baseline. ALZ, Alemtuzumab; CLA, cladribine; DMF, dimethyl fumarate; DMT, disease-modifying treatment; NTZ, natalizumab; OCR, ocrelizumab; S1P, sphingosine-1-phosphate receptor modulator; TER, teriflunomide
Fig. 3
Fig. 3
Time to DMT escalation depending on patients’ sex. To visualize the interaction effect of sex and ARR on DMT on the probability of DMT escalation, we computed the estimated Cox regression survival probabilities separately for male and female pwMS according to the occurrence of relapse (no relapse versus relapse > 1). In addition, DMT was set to “DMF”, pre-treatment “yes”, baseline MRI T2 lesion load “ > 9” and EDSS progression “no”. All other parameters (age, disease duration, pre-ARR, baseline EDSS) were set to their median values. ARR, annualized relapse rate; DMT, disease-modifying treatment; EDSS, Expanded Disability Status Scale; DMF, dimethyl fumarate
Fig. 4
Fig. 4
Time to mDMT discontinuation depending on patients’ sex and age. To visualize the interaction effect of sex and age on the probability of treatment discontinuation, we computed the estimated Cox regression survival probabilities for male (left panel) and female pwMS (right panel), each separately for mature (age set at 55 years) and young pwMS (age set at 25 years). In addition, DMT was set to “DMF”, pre-treatment “yes”, baseline MRI T2 lesion load “ > 9”, EDSS progression “no” and ARR on DMT “0”. All other parameters (disease duration, pre-ARR, baseline EDSS) were set to their median values. ARR, annualized relapse rate; DMF, dimethyl fumarate; DMT, disease-modifying treatment; EDSS, Expanded Disability Status Scale; mDMT, moderate-efficacy DMT
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