Search

Background: Alemtuzumab is approved in the European Union for treating highly active relapsing-remitting multiple sclerosis (RRMS). Patient-reported outcomes measure the treatment impact on quality of life (QoL), including fatigue, a common symptom in multiple sclerosis (MS). Chronic diseases like MS also affect the patient's caregiver. Thus, understanding the impact on both patients and caregivers is essential for a comprehensive view of MS treatment outcomes., Methods: This multi-center prospective, observational study assessed RRMS patients undergoing alemtuzumab treatment, and their caregivers across three European countries (Denmark, Norway, and Italy). The study visits were conducted at baseline, and at Months 3, 6, 12, 18, 24, and 36 (± 1 month). The primary endpoint assessed the effect of alemtuzumab on MS-related fatigue (Fatigue Scale for Motor and Cognitive Functions [FSMC] score). Secondary endpoints included changes in cognition (Symbol Digit Modalities Test [SDMT]), depression (Beck Depression Inventory-Version II [BDI-II]), QoL (29-item Multiple Sclerosis Impact Scale [MSIS-29]), treatment satisfaction (Treatment Satisfaction Questionnaire for Medication [TSQM]), working capacity/daily life activity (Health-Related Productivity Questionnaire [HRPQ]), and clinical evaluation (number of relapses, improvement in Expanded Disability Status Scale [EDSS] score, and need for re-treatment with alemtuzumab/any other treatment). Exploratory endpoints included caregiver perception of patient's QoL, caregiver QoL, and caregiver burden. The sample size (N = 80) was determined based on the 2-sided t-test at 5 % significance level. Data were analyzed descriptively. Safety was also evaluated., Results: Of 87 enrolled patients, 72.4 % (n = 63) completed all follow-ups. Significant improvement was observed in fatigue (p < 0.01), with a median (min, max) FSMC score change of -7.3 (-56.0, 34.0) units at the end-of-study (EOS), and clinically relevant improvement (≥ 9 units) noted in approximately 12.5 months. SDMT (3-5 units, p<0.05), BDI-II (median score of 9.5, i.e., no depression, p<0.01), and MSIS-29 (median change in physical and psychological impact scores -9.2, p < 0.01 and -14.8, p < 0.001, respectively) improved significantly from baseline to EOS. Global treatment satisfaction (p < 0.001), effectiveness (p < 0.05), and side effects (p < 0.05) significant improved exept at EOS, whereas treatment convenience remained same throughout the study. The percentage of patients with at least one relapse was similar each year of the study (10.8-13.2 %). A statistically significant improvement (p < 0.05) in EDSS was reported over time. At EOS, 4.5 % patients needed retreatment with alemtuzumab. Caregivers also reported improvement in patients' QoL over time, but the median change from baseline (physical and psychological impact scores:10.0 and -14.8, respectively) was not statistically significant (p > 0.05). Caregivers reported similar QoL and caregiver burden at baseline and EOS, apart from an increase in emotional QoL. Headache (51.2 %), pyrexia (44.2 %), and rash (34.9 %) were the most common adverse events (AEs). Majority of the AEs were either mild or moderate, apart from 25 severe AEs. Three patients discontinued prematurely, of which one patient died of sepsis related to treatment., Conclusion: This real-world study showed beneficial impact of alemtuzumab on fatigue, cognition, depression, QoL, and treatment satisfaction. Improvement in patient disability, and caregiver-reported outcomes indicated enhanced patients' QoL., Competing Interests: Declaration of competing interest Jette Lautrup Frederiksen: Served on scientific advisory boards for and received funding for travel related to these activities as well as honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis, and Almirall. Received speaker honoraria from Biogen Idec, Teva, and Novartis. Luca Massacesi: Received educational grants and/or research funds from Biogen, Merck-Serono, Genzyme, and Roche and honoraria or consultation fees from Biogen, Roche, Merck-Serono, Sanofi, Viatris, Horizon, Alexion, and Novartis. Helle Hvilsted Nielsen: Received research support, travel grants, and/or teaching honoraria from Biogen Inc., Merck Serono, Novartis, Sanofi, Teva, and Roche. Augusto Rini: Received a grant for the organization of a scientific congress or speaker honoraria from Biogen Idec, Sanofi, Merck Serono, Bristol, and Roche. Eleonora Baldi: Received a grant for the organization of a scientific congress from Biogen Idec and also received travel or speaker honoraria from Biogen Idec, Sanofi, Merck Serono, Novartis, and Roche. Massimiliano Mirabella: Reported scientific advisory board membership with Bayer Schering, Biogen, Sanofi, Merck, Novartis, and Roche; received consulting and/or speaking fees and research support or travel grants from Almirall, Alexion, Bayer Schering, Bristol-Myers-Squibb, Biogen, Janssen, Sanofi, Merck, Novartis, Roche, and Viatris; reported to be a principal investigator in clinical trials conducted by Biogen, Merck, Novartis, Roche, and Sanofi. Falzone Francesca Maria Antonella: Received travel or speaker honoraria and grants to attend scientific congresses from Biogen, Sanofi, Merck Serono, and Teva. Received a grant for the organization of a scientific congress from Biogen. Giacomo Lus: Received speaker, travel, and advisory board membership honoraria from Almirall, Alexion, Bayer, Biogen, Novartis, Sanofi, Merck, Bristol-Myers-Squibb, and Horizon Therapeutics. Damiano Paolicelli: Received speaker honoraria from Novartis, Sanofi, Biogen Idec, Merck-Serono, Roche, BMS, and Almirall. Matthias Kant: Has nothing to disclose. Giuseppe Salemi: Received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Umberto Aguglia: Received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Cristoforo Comi: Received grants to attend scientific congresses or speaker honoraria from Merck-Serono, Novartis, Roche, Sanofi, and Almirall. Milena De Riz: Received grants to attend scientific congresses or speaker honoraria from Merck-Serono, Novartis, Roche, Sanofi, Biogen, Teva, Almirall, Bristol-Myers-Squibb, and Horizon Therapeutics. Valeria Barcella: Received grants to attend scientific congresses or speaker honoraria from Biogen, Merck-Serono, Novartis, Roche, Sanofi, and Teva. Heidi Ø. Flemmen: Received unrestricted research grants from Biogen and Novartis and advisory board and/or speaker honoraria from Sanofi, Merck, and Biogen. Alessandra Protti: Has nothing to disclose. Elisabeth Farbu: Received unrestricted grants from Novartis and participated in advisory boards from Biogen, Merck, Novartis, Roche, and Sanofi. Job van Exel: Received research funds from AstraZeneca, GSK, Janssen, Merck, Novartis, Pfizer, Sanofi, and Takeda. Øivind Torkildsen: Received speaker honoraria from and served on scientific advisory boards of Biogen, Sanofi-Aventis, Merck, and Novartis., (Copyright © 2024. Published by Elsevier B.V.)

Background: Adherence is a prerequisite for the efficacy of any drug, and previous studies have shown that non-adherence is associated with disease activity and increased health care cost in multiple sclerosis (MS). The aim of this study was to investigate rates and reasons for discontinuation of dimethyl fumarate (DMF) among people with MS on a national level and differences between clinics in Denmark., Methods: This was a nationwide, registry and population study of patients treated with DMF. We calculated standard residuals (SR) demonstrate differences between clinics. For survival analysis regarding discontinuation rates and discontinuation due to specific AEs we used log-rank test Cox-proportional hazards and plotted Kaplan-Meier graphics., Results: We included 2,448 people with MS, treated with DMF from 2013 to 2020. Average treatment duration was 26 months (5,382 treatment years). 49.2 % of patients who initiated treatment with DMF (n = 1205) were continuously treated. Reasons for discontinuation were adverse events (54.5 %, n = 656), active disease (26.1 %, n = 315), pregnancy (9.4 %, n = 113) or other reasons (13.2 %, n = 159). We compared SR to the mean regarding reasons for discontinuation and found significant differences between sites regarding gastrointestinal adverse events, flushing and lymphopenia. Discontinuation due to all adverse events, flushing and lymphopenia were more frequent in female than male patients., Conclusion: In this population-based study, we found major differences between the MS clinics in rates and reason for discontinuation of DMF. Our results suggest that management strategies during DMF treatment can reduce discontinuation rates., Competing Interests: Declaration of Competing Interest M Stilund has served on scientific advisory boards for Sanofi, received support for congress participation or received speaker honoraria from Biogen, Teva, Merck, Roche and Sanofi. M. Stilund has eceived grants for his research from Novartis, and is currently engaged in sponsor-initiated research projects by Bayer, Jansen, Shionogi and Sanofi. J Schäfer has served on a scientific advisory board with Sanofi, received speaker honoraria from Novartis and travel compensation for congress participation from Merck, Roche and Sanofi. R Ratzer has served on scientific advisory boards, received speaker honoraria and received support for congress participation from Merck, Sanofi, Roche, Medtronic and Ipsen. Á Theódórsdóttir has served on scientific advisory boards for Roche and Sanofi and steering committee for Novartis, received research grand from Novartis and Sanofi, and has received support for congress participation from Roche, Biogen, Novartis, Merck and Sanofi. ÁT is currently engaged in sponsor-initiated research projects by Novartis and Roche. F Sellebjerg has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche and Sanofi Genzyme. His-laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. T Sejbaek received has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Biogen, Merck, Novartis, Roche and Sanofi. T. Sejbaeks received unrestricted research grants to his research institution from Biogen, Merck and Roche, and is currently engaged in sponsor-initiated research projects by Eisai, Lundbeck, Roche and Sanofi. All other authors have no conflicts of interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Natalizumab is a widely used high-efficacy treatment in multiple sclerosis (MS). Real-world evidence regarding long-term effectiveness and safety is warranted. We performed a nationwide study evaluating prescription patterns, effectiveness, and adverse events., Methods: A nationwide cohort study using the Danish MS Registry. Patients initiating natalizumab between June 2006 and April 2020 were included. Patient characteristics, annualized relapse rates (ARRs), confirmed Expanded Disability Status Scale (EDSS) score worsening, MRI activity (new/enlarging T2- or gadolinium-enhancing lesions), and reported adverse events were evaluated. Further, prescription patterns and outcomes across different time periods ("epochs") were analysed., Results: In total, 2424 patients were enrolled, with a median follow-up time of 2.7 years (interquartile range (IQR) 1.2-5.1). In recent epochs, patients were younger, had lower EDSS scores, had fewer pre-treatment relapses and were more often treatment naïve. At 13 years of follow-up, 36% had a confirmed EDSS worsening. On-treatment ARR was 0.30, corresponding to a 72% reduction from pre-initiation. MRI activity was rare, 6.8% had activity within 2-14 months from treatment start, 3.4% within 14-26 months, and 2.7% within 26-38 months. Approximately 14% of patients reported adverse events, with cephalalgia constituting the majority. During the study, 62.3% discontinued treatment. Of these, the main cause (41%) was due to JCV antibodies, while discontinuations due to disease activity (9%) or adverse events (9%) were less frequent., Conclusion: Natalizumab is increasingly used earlier in the disease course. Most patients treated with natalizumab are clinically stable with few adverse events. JCV antibodies constitute the main cause for discontinuation., Competing Interests: Declaration of Competing Interest MD Buron has received speaker honoraria from Novartis. F Sellebjerg has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, H. Lundbeck A/S, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from , Merck, Novartis, Roche and Sanofi Genzyme. M Magyari has served in scientific advisory board for Sanofi, Novartis, Merck, and has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, Bristol Myers Squibb. J Romme Christensen has received speaker honoraria from Biogen. PV. Rasmussen has received speaker honoraria from TEVA, Biogen, Roche and Novartis, support for congress participation from Merck, Roche, Sanofi and TEVA, fees for serving on advisory boards from Merck, Roche, Novartis, Biogen, and Sanofi. PS. Sorensen has received personal compensation for serving on advisory boards for Biogen, Merck, Novartis, Teva; on steering committees or independent data monitoring boards in trials sponsored by Merck, and Novartis; and has received speaker honoraria from Biogen, Merck, Teva, BMS/Celgene, and Novartis. H Joensen, M Kant, D Bech and L Pontieri report no disclosures, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Dimethyl fumarate (DMF, Tecfidera®) is a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis. Lymphopenia is a frequent reason for discontinuation in fumarate-treated patients. Management strategies to minimize risk of lymphopenia are warranted., Objective: The aims of this study were to investigate the correlation of body mass index (BMI), baseline absolute lymphocyte count (ALC), age and sex with risk of DMF-induced lymphopenia in MS patients., Methods: The study was a retrospective cohort study of 452 MS patients who had been prescribed DMF at six clinics in two Danish regions between May 2014 and September 2017. Data on lymphocyte counts, BMI, age, sex, and reason for discontinuation of DMF were collected through the Danish Multiple Sclerosis Registry, with follow- up to two years after treatment start., Results: 28.5% of patients had lymphopenia grade II or higher at some time in the first two years of DMF treatment. Increased risk of lymphopenia was observed in patients with baseline ALC of 1.00-1.49×10 9 cells/L (odds ratio, OR 5.48, p<0.0001) and 1.50-1.99×10 9 cells/L (OR 2.08, p = 0.0009). Reduced risk of lymphopenia was observed in patients with ALC of 2.00-2.49×10 9 cells/L (OR 0.51, p< 0.01) and ≥ 2.50×10 9 cells/L (0.12, p<0.0001). Patients aged ≥ 56 years had an increased risk of lymphopenia (OR 3.58, p<0.001), and patients with BMI ≥ 30 kg/m 2 had a decreased risk of lymphopenia (OR 0.53, p value = 0.03)., Conclusion: Low baseline ALC and older age were risk factors for DMF-induced lymphopenia, while BMI ≥ 30 kg/m 2 and high baseline ALC were protective factors for developing lymphopenia in MS patients treated with DMF., (Copyright © 2022. Published by Elsevier B.V.)

Background: Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting., Methods: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals., Results: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naïve and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations., Conclusion: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies., (Copyright © 2022. Published by Elsevier B.V.)

Background: The number of patients with relapsing remitting multiple sclerosis (RRMS) who convert to secondary progressive (SP) MS is uncertain, and with emerging treatment options for SPMS, it is important to identify RRMS patients in transition to the SP phase. The objective of the present study was to characterize clinical parameters and use of disease modifying therapies in patients diagnosed with SPMS and RRMS patients already entered the SP phase by use of the Danish Multiple Sclerosis Registry (DMSR)., Methods: We used a cross-sectional design, including all living patients with MS as of June 30, 2020 from DMSR. First, we applied the MSBase definition of SPMS on all RRMS patients. Second, we applied the slightly modified inclusion criteria from the EXPAND clinical trial on patients with clinically confirmed SPMS and patients with RRMS fulfilling the MSBase definition of SPMS to identify SPMS patients recently progressed who may benefit from treatment with disease modifying therapy. We compared clinical characteristics and disease-modifying therapy use in the different patient groups., Results: Among patients with clinically confirmed SPMS, application of a slightly modified EXPAND trial inclusion criteria for SPMS (m-EXPAND) captured patients who had converted to SPMS more recently and who had relapsed and initiated high-efficacy treatment more frequently. Moreover, our RRMS patients fulfilling the "SPMS"-criteria according to MSBase and recently progression according to m-EXPAND had similar characteristics and remarkably resembled the SPMS population in the EXPAND trial., Conclusion: Our results indicate that data-driven diagnostic definitions might help identify RRMS patients at risk for SPMS and we highlight the challenges and reluctance in diagnosing SPMS in clinical practice., (Copyright © 2021. Published by Elsevier B.V.)