- |||||||||| Tysabri (natalizumab) / Biogen, Royalty
A Retrospective Analysis of Disease Modifying Drug Discontinuation in Patients with Multiple Sclerosis (Colorado Convention Center | Mile High 2/3) - Mar 8, 2024 - Abstract #AAN2024AAN_4340;
Patients who developed disease activity after discontinuing DMD were younger (mean age 48)compared to patients who remained with no disease activity (mean age 60) and had loweraverage EDSS scores (2.8 vs 3.58). Patients who discontinued fingolimod and natalizumab wereat higher risk of disease activity after treatment discontinuation (58% and 30%, respectively).Finally, patients > 60 years and EDSS > 6 were at the lowest risk of disease activity afterdiscontinuation.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Longer-term (Up to 6 Years) Efficacy of Ofatumumab in People with Recently Diagnosed and Treatment-naive Relapsing Multiple Sclerosis (Colorado Convention Center | Mile High 2/3) - Mar 8, 2024 - Abstract #AAN2024AAN_4333;
Patients who discontinued fingolimod and natalizumab wereat higher risk of disease activity after treatment discontinuation (58% and 30%, respectively).Finally, patients > 60 years and EDSS > 6 were at the lowest risk of disease activity afterdiscontinuation. Objective:To assess ofatumumab's longer-term efficacy for up to 6 years in people with recently diagnosed treatment-naive (RDTN) relapsing multiple sclerosis (RMS).Background:Ofatumumab, a fully human anti-CD20 monoclonal antibody with a 20 mg subcutaneous monthly dosing regimen, demonstrated superior efficacy and similar safety versus teriflunomide in the Phase 3 ASCLEPIOS I/II overall population and in a subgroup of RDTN participants (diagnosed ?3 years)...Ofatumumab demonstrates sustained long-term efficacy in people with RDTN RMS, supporting its use early in the disease course.
- |||||||||| Mavenclad (cladribine) / EMD Serono
Treatment Persistence of Cladribine Tablets Versus Other Oral Disease-modifying Treatments for Multiple Sclerosis: Results from Danish, Norwegian, and Swedish Registries (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_4151;
Objective:To assess ofatumumab's longer-term efficacy for up to 6 years in people with recently diagnosed treatment-naive (RDTN) relapsing multiple sclerosis (RMS).Background:Ofatumumab, a fully human anti-CD20 monoclonal antibody with a 20 mg subcutaneous monthly dosing regimen, demonstrated superior efficacy and similar safety versus teriflunomide in the Phase 3 ASCLEPIOS I/II overall population and in a subgroup of RDTN participants (diagnosed ?3 years)...Ofatumumab demonstrates sustained long-term efficacy in people with RDTN RMS, supporting its use early in the disease course. Objective:Compare real-world time-to-treatment switch and discontinuation in adult patients receiving cladribine tablets (CladT; 3.5mg/kg cumulative dose over 2 years) versus other oral disease-modifying therapies (DMTs).Background:Generating Learnings In MultiPle SclErosis (GLIMPSE) is a longitudinal study of prospectively collected registry data to compare real-world treatment outcomes in patients with relapsing multiple sclerosis treated with CladT versus other oral DMTs (fingolimod [FING], dimethyl fumarate (DMF), and teriflunomide [TER]).Design/Data from Danish, Norwegian, and Swedish multiple sclerosis registries were pooled for treatment-na
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Longer-term Safety and Efficacy of Ofatumumab in People with Relapsing Multiple Sclerosis for Up to 6 Years (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3224;
These results could be beneficial in managing disease and limiting future accumulation of disability in this population. Objective:To assess ofatumumab's longer-term safety and efficacy for up to 6 years in people with relapsing multiple sclerosis (pwRMS).Background:Ofatumumab, a fully human anti-CD20 monoclonal antibody, demonstrated superior efficacy versus teriflunomide in the Phase 3 ASCLEPIOS I/II trials in pwRMS...These analyses will help inform physicians on the longer-term safety and efficacy profile of ofatumumab in pwRMS.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Long-term Effect of Ofatumumab on Serum Immunoglobulin Levels in Patients with Relapsing Multiple Sclerosis (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3221;
P3
4 years had serum IgG and IgM levels that remained above lower limit of normal (LLN).Design/Change in IgG/IgM levels from baseline for up to 5 years of ofatumumab treatment was analyzed in the overall (N=1969), continuous (ofatumumab in core+extension; N=1292), and switch (teriflunomide in core, ofatumumab in extension; N=677) groups...With ?5 years of ofatumumab treatment, the majority of patients did not have Ig levels that dropped below the LLN at any assessment. Overall, the number of serious infections was low in patients with Ig levels that dropped below the LLN.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Baseline Serum Neurofilament Light Chain Levels Predict Future Disease Activity Irrespective of Race/Ethnicity: Results from the Phase 3 ASCLEPIOS I/II Trials (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3220;
Overall, the number of serious infections was low in patients with Ig levels that dropped below the LLN. Objective:To evaluate the prognostic value of baseline serum neurofilament light chain (sNfL) for future MRI disease activity in diverse racial/ethnic subpopulations (Asian, Black, and Other) of people with relapsing multiple sclerosis (pwRMS) in the Phase 3 ASCLEPIOS I/II trials.Background:In ASCLEPIOS I/II (ofatumumab versus teriflunomide), baseline sNfL levels were prognostic for on-study lesion formation and brain volume loss...Baseline sNfL levels were prognostic for neT2 lesion development in all pwRMS, including those of diverse racial/ethnic subpopulations.
- |||||||||| Ocrevus (ocrelizumab) / Roche, Biogen
Ocrelizumab in Patients With Early-stage RRMS (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3219;
P3
The study is limited by the short observation period while non-disabling relapses are frequent in early RRMS. The ITT approach accounted for the real-world treatment pathways and DMT switches; however, it may not fully account for the effect on disability worsening of escalation strategy to high-efficacy DMTs applied in NTD.
- |||||||||| Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm
Earlier Initiation of Ublituximab Treatment Is Associated with Improved Disability Outcomes Among Treatment Na (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3215;
The approved dose and more frequent SC administration of ofatumumab seems to cover the full spectrum of BMI in pwRMS. In post hoc analyses of ULTIMATE studies, earlier ublituximab treatment was associated with improved disability outcomes measured by EDSS and MSFC versus teriflunomide in treatment na
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono
Real-world Persistence of Ofatumumab vs Self-injectable or Oral Disease-modifying Therapies in Patients with Multiple Sclerosis (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3021;
In post hoc analyses of ULTIMATE studies, earlier ublituximab treatment was associated with improved disability outcomes measured by EDSS and MSFC versus teriflunomide in treatment na Adults diagnosed with MS and treated with ofatumumab, a platform self-injectable (glatiramer acetate, interferon ?-1a/1b, or peginterferon ?-1a), or an oral DMT (dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, ozanimod, diroximel fumarate, and monomethyl fumarate) between August 2020 and November 2021 and who had ?6 months of follow-up were included...In this real-world study with 12 months of follow-up, patients treated with ofatumumab demonstrated higher persistence vs those treated with platform self-injectable DMTs and those treated with oral DMTs.
- |||||||||| Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm
MS Relapse Redefined: Distinguishing True Relapses from Pseudoexacerbations in the ULTIMATE I and II Trials Comparing Ublituximab vs Teriflunomide (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_2475;
Adults diagnosed with MS and treated with ofatumumab, a platform self-injectable (glatiramer acetate, interferon ?-1a/1b, or peginterferon ?-1a), or an oral DMT (dimethyl fumarate, fingolimod, teriflunomide, cladribine, siponimod, ozanimod, diroximel fumarate, and monomethyl fumarate) between August 2020 and November 2021 and who had ?6 months of follow-up were included...In this real-world study with 12 months of follow-up, patients treated with ofatumumab demonstrated higher persistence vs those treated with platform self-injectable DMTs and those treated with oral DMTs. Increased stringency of MS relapse definition provides a truer assessment of clinical efficacy, and the improved signal to noise ratio of relapse outcomes has implications for relapsing MS trial design and power calculations.
- |||||||||| dimethyl fumarate / Generic mfg., teriflunomide / Generic mfg.
Conversion of Radiologically Isolated Syndrome to Multiple Sclerosis: A Meta-analysis (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_1963;
Approximately a quarter of RIS patients will convert to MS, and DMT seems to significantly reduce this rate. However, future research is needed to properly identify high-risk patients that would benefit from DMT.
- |||||||||| teriflunomide / Generic mfg., fingolimod / Generic mfg.
Preclinical, Journal, Immunomodulating: Clinically approved immunomodulators ameliorate behavioral changes in a mouse model of hereditary spastic paraplegia type 11. (Pubmed Central) - Mar 4, 2024
Translating this into a clinically applicable approach, we show that treatment with the established immunomodulators fingolimod or teriflunomide significantly attenuates distinct behavioral abnormalities, with the most striking effect on social behavior. This study links neuroinflammation to behavioral abnormalities in a mouse model of SPG11 and may thus pave the way for using immunomodulators as a treatment approach for SPG11 and possibly other complicated forms of HSP with neuropsychological involvement.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Trial completion date, Trial primary completion date: STHENOS: Open Label Randomized Multicenter to Assess Efficacy & Tolerability of Ofatumumab 20mg vs. First Line DMT in RMS (clinicaltrials.gov) - Mar 2, 2024
P3, N=186, Recruiting,
This study links neuroinflammation to behavioral abnormalities in a mouse model of SPG11 and may thus pave the way for using immunomodulators as a treatment approach for SPG11 and possibly other complicated forms of HSP with neuropsychological involvement. Trial completion date: Sep 2025 --> Jan 2026 | Trial primary completion date: Jun 2025 --> Oct 2025
- |||||||||| Journal: A comparison of clinical, utilization, and cost outcomes between oral treatments for multiple sclerosis. (Pubmed Central) - Feb 3, 2024
To compare MS outcomes, health care resource utilization, and relative costs across treatment with dimethyl fumarate (DMF), fingolimod (FG), or teriflunomide (TERI) among Medicare Advantage Prescription Drug (MAPD) plan and commercially insured beneficiaries...FG had the lowest impatient stays and emergency department visits of the 3 groups. Patients with MS initiated on FG used fewer health care resources and experienced lower ARR compared with patients on DMF and TERI.
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty, Fumaderm (dimethyl fumarate) / Biogen
Journal, HEOR: Visualizing the target estimand in comparative effectiveness studies with multiple treatments. (Pubmed Central) - Feb 2, 2024
Patients with MS initiated on FG used fewer health care resources and experienced lower ARR compared with patients on DMF and TERI. We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF)
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty
Trial completion: Tysabri Observational Cohort Study - Multiple Sclerosis (MS) Registries (clinicaltrials.gov) - Jan 31, 2024
P=N/A, N=80327, Completed,
We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) Active, not recruiting --> Completed
- |||||||||| teriflunomide / Generic mfg.
Journal: DFT Study of Interaction between Teriflunomide and ?-cyclodextrin. (Pubmed Central) - Jan 20, 2024
The discovered compounds represent excellent starting points for the development and optimization of novel DHODH inhibitors. As a result, the possibility of the use of ?-cyclodextrin for Teriflunomide delivery to the diseased cells has been established.
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Observational data, Journal, HEOR, Cost-effectiveness, Cost effectiveness: Study to Compare the Efficacy and Cost-Effectiveness of Various Disease Modifying Drugs in the Management of Multiple Sclerosis in India- An Observational Study. (Pubmed Central) - Jan 17, 2024
Rituximab, an off-label DMT, was found to be very effective. Teriflunomide was overall an effective DMT in terms of affordability, QoL balance, and an acceptable ARR reduction.
- |||||||||| Lemtrada (alemtuzumab) / Sanofi
Journal, Adverse events: Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis. (Pubmed Central) - Jan 9, 2024
Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Review, Journal: Bioavailable central nervous system disease-modifying therapies for multiple sclerosis. (Pubmed Central) - Jan 6, 2024
To our knowledge, alemtuzumab, fumarates (dimethyl, diroximel, and monomethyl), glatiramer acetates, interferons, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and teriflunomide are either limited to the periphery or insufficiently studied to confirm direct central nervous system effects in participants with multiple sclerosis. In contrast, cladribine and sphingosine 1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are central nervous system-penetrant and could have beneficial direct central nervous system properties.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Retrospective data, Review, Journal, Immunomodulating: Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. (Pubmed Central) - Jan 4, 2024
More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Briumvi (ublituximab-xiiy) / TG Therap, Neuraxpharm
Review, Journal: Ublituximab-xiiy as a treatment option for relapsing multiple sclerosis. (Pubmed Central) - Dec 17, 2023
When compared to the Phase III trials of the other two anti-CD20 mAbs (ocrelizumab and ofatumumab), ublituximab did not result with reduction of 3 or 6-month confirmed disability progression...Future data from open-label extensions are warranted. There was no significant reduction of ublituximab on whole-brain atrophy compared to teriflunomide.
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty
Journal, HEOR, Cost-effectiveness, Cost effectiveness: Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom. (Pubmed Central) - Dec 12, 2023
Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD)...Similar cost-effectiveness results were observed across sensitivity analyses. This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Retrospective data, Review, Journal, Adverse events: Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis. (Pubmed Central) - Nov 30, 2023
At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies.
- |||||||||| teriflunomide / Generic mfg.
Journal, IO biomarker: Expression of CD40 and CD192 in Classical Monocytes in Multiple Sclerosis Patients Assessed with Transcranial Magnetic Stimulation. (Pubmed Central) - Oct 28, 2023
Radiological examination on lesion detection with MRI was performed for 23 patients with relapsing-remitting MS treated with teriflunomide...The results show that in comparison to HC subjects, both pwMS with normal and altered MEP findings (prolonged MEP latency or absent MEP response) had significantly decreased surface receptor expression measured (MFIs) of CD192 and increased CD40 MFI in classical monocytes, and significantly increased percentages of classical and total monocytes positive for CD40. Knowing CD40's pro-inflammatory action, and CD192 as a molecule that enables the passing of monocytes into the brain, decreased CD192 in classical monocytes could represent a beneficial anti-inflammatory parameter.
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