Fumaderm (dimethyl fumarate) / Biogen - LARVOL DELTA

Patient and healthcare provider experience of diroximel fumarate: considerations for selecting disease-modifying therapy. (PubMed, Neurodegener Dis Manag) - "A real-world, patient-focused survey on MS treatment suggested DRF was well tolerated and associated with patient-reported physical benefits. HCP-reported reasons for selecting DRF included efficacy and tolerability issues with prior DMT."

Journal • CNS Disorders • Multiple Sclerosis

Long-Term Treatment with Fumarates versus Anti-CD20 Monoclonal Antibodies and Infection-related Outcomes in Patients with Multiple Sclerosis (ECTRIMS 2025) - " The study included 1956 PS-matched PwMS, with 652 FUM initiators (614 dimethyl fumarate, 38 diroximel fumarate) and 1304 anti-CD20 initiators (1296 ocrelizumab, 8 ofatumumab)... PwMS treated with FUM experienced significantly lower long-term infection-related HCRU compared with those on anti-CD20s, with similar relapse outcomes. The difference in infection risk between FUM and anti-CD20 therapies increased with treatment duration, consistent with prior evidence that infection risk rises with long term B-cell depletion. These findings underscore the long-term risk-benefit considerations when selecting or maintaining DMTs in MS management."

Clinical • CNS Disorders • Infectious Disease • Multiple Sclerosis

Prospective De-Escalation from B-cell Depletion to Fumarates: Interim 1-year results (ECTRIMS 2025) - "Half were on ocrelizumab, 40% on rituximab, and 10% on ofatumumab. Eight patients transitioned to diroximel fumarate (DRF) and 2 to dimethyl fumarate (DMF)... De-escalating from B-cell depleting therapies to fumarates appears to maintain efficacy early in this transition. This is a two-year study that is ongoing to better evaluate efficacy and safety of this treatment switch."

Clinical • CNS Disorders • Infectious Disease • Multiple Sclerosis

cutaneous lymphoid hyperplasia-grey case (EADV 2025) - "These included methotrexate, intralesional steroid, interferon-alpha, cyclosporine, Fumaderm, Intralesional and Intravenous Rituximab. This case demonstrates how challenging the diagnosis and treatment of idiopathic CLH can be. Dupilumab cleared effectively both eczema and CLH lesions. This case highlights a future potential role of targeted biologics and the need to explore immunomodulatory strategies in similar cases."

Clinical • Atopic Dermatitis • Dermatology • Eosinophilia • Hematological Malignancies • Infectious Disease • Inflammation • Inflammatory Arthritis • Langerhans Cell Histiocytosis • Lupus • Lyme Disease • Lymphoma • IL13 • IL4 • STAT6

Comparative Effectiveness of Fumarates Versus Sphingosine-1-Phosphate Receptor Modulators in Black Patients with Multiple Sclerosis. (PubMed, Neurol Ther) - "This real-world, claims-based analysis demonstrates that fumarates and S1P receptor modulators have similar effectiveness in reducing relapses among Black PwMS, with > 72% of patients in both treatment groups remaining relapse-free at 24 months. Given the underrepresentation of Black patients in MS clinical trials, these results provide valuable real-world evidence to guide treatment decisions for this population."

HEOR • Journal • CNS Disorders • Multiple Sclerosis

Real-World Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates in the USA. (PubMed, Neurol Ther) - "Consistent with prior studies, these results demonstrate the effectiveness of fumarates across racial and ethnic MS subgroups. This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Infographic available for this article."

HEOR • Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

Real-World Treatment Outcomes in People with Multiple Sclerosis who Switched From Teriflunomide to Fumarates (ACTRIMS Forum 2025) - "There is limited understanding of the real-world clinical disease activity and healthcare resource utilization (HRU) and healthcare costs (HCC) among pwMS who switch from teriflunomide (TERI) to fumarate (FUM; either dimethyl fumarate [DMF] or diroximel fumarate [DRF]) therapies.Objectives: To estimate pre- and post-switch annualized relapse rate (ARR), time to relapse, 1-yr pre-index vs post-index MS-related HRU and HCC in pwMS who switched from TERI to FUM. This retrospective analysis of the Komodo Health claims database included pwMS with ≥1 claim for TERI and MS diagnosis (ICD-10 code G35) between 1 Jan 2016 and 31 May 2022... ARRs decreased after switching from TERI to FUM, but was not statistically significant; however, patients had lower MS-related HRU and HCC after switching from TERI to FUM. Our results suggest FUM may be a reasonable and a cost-effective option for pwMS on prior TERI treatment.Study Supported by: Biogen"

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Real-world Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates (P4-6.005). (PubMed, Neurology) - "Dimethyl fumarate (DMF) and diroximel fumarate (DRF) are disease-modifying therapies for relapsing MS...Dr. Shankar has stock in Biogen."

HEOR • Journal • Real-world evidence • Retrospective data • CNS Disorders • Multiple Sclerosis

LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France. (PubMed, Adv Ther) - P=N/A | "LymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit-risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution."

Clinical • Journal • Real-world evidence • Retrospective data • CNS Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Multiple Sclerosis • Rare Diseases

Chemoproteomic Profiling of Clickable Fumarate Probes for Target Identification and Mechanism of Action Studies. (PubMed, ACS Chem Biol) - "To better understand the mechanism of action of DMF and its active metabolite, monomethyl fumarate (MMF), we designed and utilized clickable probes to visualize and enrich probe-modified proteins. We further perform quantitative chemoproteomics analysis for proteome-wide target identification and validate several unique and shared targets of DMF and MMF, which provide insight into the reactivity, selectivity, and target engagement of fumarates."

Journal • CNS Disorders • Multiple Sclerosis

Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study. (PubMed, Neurol Ther) - P=N/A | "DMF demonstrated a safety profile in real-world clinical practice consistent with the known profile of DMF. Relapse rates were low and both ARR and PROs remained stable over time."

Journal • CNS Disorders • Fatigue • Gastrointestinal Disorder • Infectious Disease • Multiple Sclerosis

Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients. (PubMed, Adv Ther) - P=N/A, P3 | "ESTEEM found no unexpected safety signals in older patients and annualized relapse rates (ARRs) were significantly reduced in both age groups. Both studies indicated that DMF is efficacious and has a favorable safety profile in patients with RRMS aged ≥ 50 years."

Journal • P3 data • P4 data • Real-world • Real-world evidence • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Multiple Sclerosis • CD4 • CD8

Patient-reported disability progression outcomes among patients with multiple sclerosis: Results of an outcomes-based agreement. (PubMed, J Manag Care Spec Pharm) - "Of the remaining 184 eligible patients (107 on dimethyl fumarate and 77 on interferon β-1a), 21 (11%) patients had confirmed disability progression (6 on dimethyl fumarate [5.6%] and 15 on interferon β-1a [19.5%]). Our findings suggest that meaningful patient-reported outcomes, such as disability progression, can be operationalized in an innovative OBA."

Journal • CNS Disorders • Multiple Sclerosis • IFNB1

A case of cutaneous and osteosarcoidosis successfully treated with Tofacitinib (EADV 2024) - "Since diagnosis in 2001 via skin biopsy; treatment had been unsuccessful, provided short lived benefit or was poorly tolerated (due to recurrent infections) with Certolizumab, Adalimumab, Infliximab, Hydroxychloroquine, Leflunomide, Methotrexate, Mycophenolate mofetil, Minocycline, Azathioprine, Fumaderm, Thalidomide, Phototherapy (PUVA) and Pentoxifylline. Tofacitinib is a JAKi approved for the treatment of inflammatory arthropathies and ulcerative colitis. JAK proteins are associated with cell surface cytokine receptors, and so are early mediators of cell response to inflammation whereby STAT driven transcription is initiated. In sarcoidosis, it is predominantly Type 1 inflammatory cytokines and interferon gamma that bind to JAK associated cytokine receptors1."

Clinical • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Rheumatology • Sarcoidosis • Ulcerative Colitis • IFNG

A 2-stage model of heterogenous treatment effects for brain atrophy in multiple sclerosis utilizing the MS PATHS research network. (PubMed, Mult Scler Relat Disord) - "The relative benefit of selecting higher efficacy treatments may vary depending on patients' baseline brain atrophy risk. Poor outcomes are predicted in individuals with high baseline risk who are treated with low-efficacy DMTs."

Journal • CNS Disorders • Multiple Sclerosis

Clinical Characteristics and Treatment Outcomes in Patients With Multiple Sclerosis Treated With Natalizumab Who Switched to Moderate-Efficacy Oral Disease-Modifying Therapies (CMSC 2024) - "OBJECTIVES: This analysis estimated annualized relapse rate (ARR), time to first relapse, health care encounters (HCEs), and health care costs (HCCs) in patients with stable MS who switched from NTZ to FUM (dimethyl fumarate/diroximel fumarate) vs those who switched from NTZ to S1Ps (fingolimod/siponimod/ponesimod/ ozanimod)... These data provide real-world clinical characteristics as well as treatment outcomes of patients with stable MS who switched from NTZ to FUM or S1Ps; after PS matching, no significant differences were observed in relapse outcomes, HCEs, or HCCs."

Clinical • Late-breaking abstract • CNS Disorders • Multiple Sclerosis

Patterns of disease-modifying therapy utilization before, during, and after pregnancy and postpartum relapses in women with multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "DMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. The proportion of pwMS experiencing a moderate/severe relapse and number of relapses declined over pregnancy but increased postpartum. Reinitiation of DMT during the postpartum period was associated with lower risk of relapses, supporting a role for early reinitiation of DMT postpartum."

Journal • CNS Disorders • Depression • Mood Disorders • Multiple Sclerosis • Postpartum Depression • Psychiatry

Evaluating the effect of dimethyl fumarate on subclinical biomarkers in a real-world patient cohort. (PubMed, J Neuroimmunol) - "Results of this real-world study were consistent with previous DMF phase III clinical trials, supporting the generalizability of the effects observed in clinical trials to the real-world clinical setting."

Biomarker • Journal • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Early on-treatment NfL levels are associated with MRI changes up to 4 years in dimethyl-fumarate treated RRMS patients (EAN 2024) - P4 | "In DMF-treated patients, higher plasma-NfL levels measured between 6 and 12 months are associated with subsequent lesion activity and brain atrophy, suggesting that NfL could be used additionally to MRI in the management of MS."

Clinical • Multiple Sclerosis • GFAP • NEFL • Plasma NfL

Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study. (PubMed, Neurol Ther) - P3 | "In DRF-treated patients in EVOLVE-MS-1, clinical and radiological measurements indicated reduced disease activity regardless of lymphopenia or magnitude of ALC decline from baseline; however, patients who had greater ALC declines appeared to have numerically lower ARR and higher proportions free from relapses and gadolinium-enhancing lesions compared with those with smallest decline. This supports prior evidence that, while lymphopenia may contribute to fumarate efficacy outcomes, it is not the primary mechanism of action."

Journal • Lymphopenia • CNS Disorders • Multiple Sclerosis

Switching disease-modifying therapies from sphingosine-1-phosphate receptor modulators to natalizumab or dimethyl fumarate restores immune responses after SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis. (PubMed, Clin Neurol Neurosurg) - "SARS-CoV-2 mRNA vaccination is expected to be effective in patients whose lymphocyte counts have recovered due to switching DMTs from S1P receptor modulators. Switching DMTs from S1P receptor modulators to NTZ before vaccination may be beneficial in achieving efficacy for SARS-CoV-2 mRNA vaccination, with a reduced risk of relapse."

Journal • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease • Respiratory Diseases • CD4

Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study. (PubMed, Adv Ther) - P3 | "In EVOLVE-MS-1, after re-baselining at approximately 7 weeks, approximately half of DRF-treated patients achieved NEDA-3 at week 96, compared with 36.5% of patients who were not re-baselined. Re-baselining may be useful for assessing efficacy of DMTs by mitigating the influence of disease activity prior to the onset of efficacy."

Journal • P3 data • CNS Disorders • Multiple Sclerosis

Characterizing Changes in Disability and Multiple Sclerosis Symptom Severity in NARCOMS Registry Participants With Multiple Sclerosis After 1 Year of Treatment With Diroximel Fumarate (CMSC 2024) - "Most participants had switched to DRF from DMF, and mean age was older than observed in clinical trials. After 1 year on DRF, most participants experienced either stability or improvement on patient-reported measures of symptom severity and disability."

CNS Disorders • Depression • Mood Disorders • Multiple Sclerosis • Pain • Psychiatry

Comparative effectiveness of dimethyl fumarate versus non-specific immunosuppressants: Real-world evidence from MSBase. (PubMed, Mult Scler J Exp Transl Clin) - "To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022...The DMF cohort experienced longer times to discontinuation (HR: 0.75; p = 0.001) and CDP (HR: 0.53; p = 0.001), and shorter time to CDI (HR: 1.99; p < 0.008), versus the NSIS cohort. This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS."

HEOR • Journal • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis

Change in Disease Modifying Therapy from DMF to DRF in People with Multiple Sclerosis and the Impact on CD4/CD8 T Cells (AAN 2024) - "Diroximel fumarate (DRF) and dimethyl fumarate (DMF) convert to the same active metabolite, monomethyl fumarate (MMF), but DRF has an improved tolerability profile due to its unique chemical structure...PwMS who switched from DMF to DRF showed a statistically significant decrease in CD4 T cells over 1 year, with this shift becoming evident after 9-12 months of treatment. PwMS who switched from DMF to DRF showed a statistically significant decrease in CD8 T cell count over 1 year of treatment, with the shift becoming evident after 3 months of treatment. Changes in T cell subsets in patients treated with DRF were not associated with an increase in infections."

CNS Disorders • Immunology • Infectious Disease • Inflammation • Multiple Sclerosis • CD4