Real-Word Effectiveness and Safety of Dimethyl Fumarate in a Multiple Sclerosis Portuguese Population

Abstract

Objectives The aim of this study was to evaluate postmarketing dimethyl fumarate (DMF) safety and effectiveness in a real-world population with relapsing-remitting multiple sclerosis (RRMS). Methods This was a retrospective, single-center study with RRMS patients treated with DMF. Demographic, clinical, and imagiological characteristics were analyzed, including annualized relapse rate (ARR), Expanded Disability Status Scale, “No Evidence of Disease Activity 3,” previous treatment, adverse events, treatment duration, and reason for discontinuation. We investigated which baseline variables were associated with clinical and radiological outcomes. Results We included 176 patients (70.4% females) with a median on-treatment follow-up time of 25.5 months. In total, 139 patients received prior disease-modifying therapies, and 37 were treatment-naive. Annualized relapse rate decreased by 77.1% in the total population (P < 0.001) and also decreased in the naive, tolerability switch, and efficacy switch groups by 95.8%, 56.7%, and 76.6% (P < 0.001). No Evidence of Disease Activity 3 status after 12 months of DMF treatment was maintained in 69.2% patients. Thirty patients (17%) discontinued treatment because of adverse drug reactions, and 21 (11.9%) because of lack of effectiveness. The occurrence of first relapse during follow-up was associated with higher ARR in the year before DMF start (hazard ratio, 4.833; P < 0.001) and prior exposure to multiple sclerosis treatments (tolerability and efficacy switchers). Conclusions In this real-world audit, DMF appeared to be effective and safe for RRMS. Additionally, the study suggested that naive patients strongly benefit from DMF, and DMF also improves ARR in patients who switched from injectable therapies due to tolerability and efficacy issues.

Safety and Discontinuation Rate of Dimethyl Fumarate (Zadiva®) in Patients with Multiple Sclerosis: An Observational Retrospective Study

“…However, a retrospective study by Vollmer et al reported GI disorders in 80.5% of patients [13]. Similarly, a single-center study by Barros et al reported a 42% incidence of GI disorders, with abdominal pain, diarrhea, nausea, and vomiting occurring in 26.7%, 14.8%, 9.6%, and 5.7% of patients, respectively [14,15]. Our study highlights the importance of monitoring adverse events in patients receiving DMF and the potential benefits of a slow dose titration to improve the tolerability of this treatment.…”

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method

“…28 Outside pivotal clinical trials, these findings are further supported by observational studies of patients switching from other first-line therapies to DMF. 122,124,132,[146][147][148][149][150][151] Based on these results, horizontal switching, especially from injectable therapies, is a viable use of DMF.…”

Multipl Skleroz Hastalarında Dimetil Fumarat: Bir Gerçek Yaşam Çalışması

“…Literatür incelendiğinde daha önce başka HMT kullanım oranlarının benzer şekilde %58-%90 arasında olduğu ve YRH'ların 0,5-0,76 arasında bildirildiği görülmüştür. 6,[10][11][12][13][14][15][16] Diğer kohortlar ile büyük oranda benzer olan çalışmamız DMF'nin daha çok ikinci basamakta tercih edildiğini göstermektedir. DMF tedavisi esas olarak birinci basamakta kullanılmak üzere onay almıştır.…”

“…Ek olarak daha kısa hastalık süresi olan hastalarda daha yüksek etkinlik ve tedavi olduğu da başka çalışmalarda da bildirilmektedir. 10,13 Çalışmamızda da benzer bulgular elde edilmiştir. DMF öncesi EDSS değerlerine bakıldığında hasta kohortumuzda medyan 2.0 EDSS değeri başka kohortlarla benzer olsa da 13,15 , bazılarına göre daha yüksektir.…”

“…DMF öncesi EDSS değerlerine bakıldığında hasta kohortumuzda medyan 2.0 EDSS değeri başka kohortlarla benzer olsa da 13,15 , bazılarına göre daha yüksektir. 10 Hastaların DMF öncesinde EDSS skorunun 3'ten büyük olması, ilaç başlandıktan sonra yaşanan ilk atağın daha erken olmasına, özürlülüğün daha erken artmasına ve dolayısı ile NEDA durumunun daha erken kaybolmasına yol açmıştır. Bu veri EDSS 3 düzeyine ulaşmış olan hastalarda DMF'nin daha etkisiz olabileceğini düşündürmektedir.…”