- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Journal: Clinical Profile and Treatment Outcome in MOGAD: A Single-Center Case-Series Study in Guiyang, China. (Pubmed Central) - Apr 26, 2022
Intravenous methylprednisolone (IVMP) was administrated for 85% of the attacks while both IVMP and intravenous immunoglobulin were for 6% of the attacks...Among them, six patients were treated with mycophenolate mofetil, three patients were treated with prednisone, rituximab, and teriflunomide, respectively...The long-term outcome of MOGAD seems benign. Further studies are warranted to determine the risk factors of relapse and identify the optimal steroid-sparing agents.
- |||||||||| IMPACT OF IMMUNOSUPPRESSIVE THERAPIES ON ANTIBODY DECAY FOLLOWING MRNA VACCINATION TO SARS-COV-2 IN A PROSPECTIVE COHORT OF PATIENTS WITH CHRONIC INFLAMMATORY DISEASES (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_2976;
The impact of various medications was assessed in repeated measures mixed model with the patient as a random effect, adjusting for gender and age, and using the group of patients on sulfasalazine, NSAIDs, or on no medications as a reference, using STATA...The strongest decline was observed among patients on B cell depleting/modulating therapies followed by those on combinations of biologics and/or small molecules and antimetabolites (methotrexate, leflunomide, thiopurines, mycophenolate mofetil, and teriflunomide)...Our data and those from other cohorts may be used to prioritize medication classes for boosting immunogenicity with additional doses of vaccination against SARS-CoV-2. Collection of antibody titers after booster doses is currently ongoing.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
CLINICAL CHARACTERISTICS, DISEASE-SPECIFIC OUTCOMES, AND MEDICATION UTILIZATION AMONG PATIENTS WITH CHRON’S DISEASE AND MULTIPLE SCLEROSIS IN THE USA: A MULTICENTER NETWORK STUDY (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_1705;
CD patients with MS were also more likely to use the following MS DMTs: natalizumab, glatiramer, interferon beta-1a and 1b, fingolimod, teriflunomide, dimethyl fumarate, ocrelizumab, and ofatumumab (Table 1).Three months after any IBD therapy initiation, CD patients with MS were more likely to need plasma exchange and undergo small intestine resections but were less likely to have fistulizing disease...Interestingly, they were also more likely to be prescribed TNF alpha-inhibitors. Future directions include stratifying the association with anti-TNFs from a temporal perspective and in terms of IBD and MS severity.
- |||||||||| teriflunomide / Generic mfg.
Trial completion date, Trial primary completion date: An Observational Study on Teriflunomide-exposed Pregnancies (clinicaltrials.gov) - Apr 25, 2022
P=N/A, N=325, Recruiting,
Future directions include stratifying the association with anti-TNFs from a temporal perspective and in terms of IBD and MS severity. Trial completion date: Dec 2022 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Jun 2023
- |||||||||| Ocrevus (ocrelizumab) / Roche, Biogen
Journal: Prediction of multiple sclerosis outcomes when switching to ocrelizumab. (Pubmed Central) - Apr 22, 2022
Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months)...Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
P3 data, Journal: Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials. (Pubmed Central) - Apr 19, 2022
High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p<0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, -0.32% vs. -0.24%, p=0.044, and teriflunomide, -0.43% vs. -0.29%, p=0.002), thalamic volume (-0.56% vs. -0.31%, p=0.047 and -0.94% vs. -0.49%, p<0.001), and WM volume (-0.30% vs. -0.19%, p=0.083 and -0.38% vs. -0.18%, p=0.003) but not of cGM volume (-0.39% vs. -0.32%, p=0.337 and -0.49% vs. -0.46%, p=0.563)...Results were similar in the subgroup of recently diagnosed, treatment-naive patients. This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Journal: Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy). (Pubmed Central) - Apr 15, 2022
Following emergency admission, older age was associated with probability of death (n = 63) (odds ratio (OR) = 1.06; p < 0.01) and discharge to long-term facility (n = 65) (OR = 1.03; p = 0.01). With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab, Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Journal: Safety and Monitoring of the treatment with Disease-Modifying Therapies for Multiple Sclerosis. (Pubmed Central) - Apr 15, 2022
Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS) are widely used given their proven efficacy in the relapsing form of the disease, while recently Siponimod and Ocrelizumab have been approved for the progressive forms of the disease...Special attention was paid to guidelines and papers focusing on the safety and monitoring of DMTs. Data for oral (Sphingosine 1-phosphate (S1P) receptor modulators, Fumarates, Teriflunomide, Cladribine), injectables (Interferons, Glatiramer acetate, Ofatumumab), and infusion therapies (Natalizumab, Ocrelizumab, Alemtuzumab) are presented.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Emergency medical care for multiple sclerosis: A five-year population study in the Campania Region (South Italy) (Room Istanbul) - Apr 9, 2022 - Abstract #EAN2022EAN_1143;
Data for oral (Sphingosine 1-phosphate (S1P) receptor modulators, Fumarates, Teriflunomide, Cladribine), injectables (Interferons, Glatiramer acetate, Ofatumumab), and infusion therapies (Natalizumab, Ocrelizumab, Alemtuzumab) are presented. With 17% people with MS requiring emergency medical care over 5 years, improved management of DMTs and comorbidities could potentially reduce their medical, social and financial burden.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Longer-term Safety of Ofatumumab in Patients With Relapsing Multiple Sclerosis (Room Oslo) - Apr 9, 2022 - Abstract #EAN2022EAN_941;
Safety findings for upto 3.5 years showed ofatumumab treatment to be well-tolerated with no new safety risks identified. This additional safety data up to 4 years will inform physicians on the longer-term safety profile of ofatumumab in RMS patients.
- |||||||||| Mayzent (siponimod) / Novartis
Assessing the immune response to SARS-CoV-2 mRNA vaccines in SPMS patients treated with siponimod (clinical trial) (Room Oslo) - Apr 9, 2022 - Abstract #EAN2022EAN_940;
Cohort 1 receives SARS-CoV-2 mRNA vaccination during continuous siponimod treatment, cohort 2 interrupts siponimod treatment for the purpose of a full vaccination cycle and cohort 3 is vaccinated during continuous treatment with first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine... This analysis will provide data on the maintenance of humoral and cellular immune response after SARS-CoV-2 vaccination in siponimod treated patients and enable physicians and patients to make an informed decision on the coordination of SARS-CoV-2 mRNA (booster) vaccination and SPMS treatment.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Improvement in Cognitive Processing Speed with Ofatumumab in Patients with Relapsing Multiple Sclerosis (Room Oslo) - Apr 9, 2022 - Abstract #EAN2022EAN_937;
Ofatumumab was associated with more clinically meaningful improvements in CPS versus teriflunomide when measured by change in SDMT in both the overall and RD populations. Early treatment initiation with ofatumumab may enhance CPS improvement in patients with RMS by efficiently suppressing inflammation.
- |||||||||| Tysabri (natalizumab) / Biogen, Royalty, Ocrevus (ocrelizumab) / Roche, Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Serum NfL and GFAP biomarker analysis in early high versus low efficacy DMT paradigms for MS (B3) - Apr 9, 2022 - Abstract #EAN2022EAN_891;
Patients enrolled in the CLIMB study treated with HEET (fingolimod, natalizumab, ocrelizumab, rituximab) or LEET (dimethyl fumarate, glatiramer acetate, interferons, teriflunomide) within five years of symptoms onset were divided into two cohorts... On-treatment levels of sNfL and sGFAP may differ in HEET vs. LEET treatment paradigms, and sGFAP is associated with disease progression.
- |||||||||| teriflunomide / Generic mfg.
Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: post-marketing data from 2018-2021 (B1) - Apr 9, 2022 - Abstract #EAN2022EAN_708;
The REMODEL I/II studies will investigate the efficacy, safety, and tolerability of remibrutinib versus teriflunomide to support regulatory approval worldwide as a potential new oral treatment for patients with this disabling disease. Reported cases from post-marketing experience did not reveal specific patterns or trends for abortion or birth defects, and do not change the overall assessment of outcomes of teriflunomide-exposed pregnancies.
- |||||||||| Ocrevus (ocrelizumab) / Roche, Biogen
Adipokine levels in multiple sclerosis patients of the same age: associations with clinical and radiological measures (B1) - Apr 9, 2022 - Abstract #EAN2022EAN_702;
Resistin and leptin levels did not differ between MS patients and HC, however, resistin levels were significantly reduced in patients using teriflunomide compared to patients using glatiramer acetate, dimethyl fumarate or ocrelizumab. Adipokines are associated with clinical and radiological measures, indicating that adipokines are promising biomarkers for disease severity in MS.
- |||||||||| Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
Longer-term Efficacy of Ofatumumab in Patients with Relapsing Multiple Sclerosis (B2) - Apr 9, 2022 - Abstract #EAN2022EAN_531;
Adipokines are associated with clinical and radiological measures, indicating that adipokines are promising biomarkers for disease severity in MS. These analyses will provide further insights on longer-term efficacy of continuous ofatumumab treatment for up to 4 years, and the effects of switching from teriflunomide to ofatumumab and add valuable information for the assessment of Ofatumumab's benefit/risk profile.
- |||||||||| teriflunomide / Generic mfg.
Teriflunomide in paediatric patients with relapsing multiple sclerosis: results from the open-label TERIKIDS extension (Room Istanbul) - Apr 9, 2022 - Abstract #EAN2022EAN_260;
P3
These analyses will provide further insights on longer-term efficacy of continuous ofatumumab treatment for up to 4 years, and the effects of switching from teriflunomide to ofatumumab and add valuable information for the assessment of Ofatumumab's benefit/risk profile. Continuous teriflunomide versus delayed teriflunomide initiation in paediatric patients numerically lowered relapse risk and disability progression, and significantly reduced MRI lesion counts with a manageable safety profile.
- |||||||||| teriflunomide / Generic mfg., leflunomide / Generic mfg.
Journal: Expanding the Repertoire of Low-Molecular-Weight Pentafluorosulfanyl-Substituted Scaffolds. (Pubmed Central) - Apr 8, 2022
A subsequent focused approach led to synthesis of analogues of the clinically used disease modifying anti-rheumatic drugs (DMARDs), Teriflunomide and Leflunomide, considered for potential COVID-19 use, where SF bioisostere deployment led to improved inhibition of HDHODH compared with the parent drugs. The results demonstrate the utility of the SF group in medicinal chemistry.
- |||||||||| leflunomide / Generic mfg.
PK/PD data, Preclinical, Journal: Effects of Paeoniflorin-6'-O-benzene sulfonate on the pharmacokinetics, excretion, and tissue distribution of leflunomide in rats. (Pubmed Central) - Apr 5, 2022
Oral CP-25 administration in combination with LEF was found to promote TER excretion in urine, feces, and bile, and to reduce its contents in most tissues and organs, especially in the liver, which may reduce LEF-induced liver injury. CP-25 also increased TER exposure in the synovium and its absorption by PBMCs, and this could explain the synergistic effects of CP-25 and LEF.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie, Lemtrada (alemtuzumab) / Sanofi
Journal: Decreased Intrathecal Concentrations of Free Light Chains Kappa in Multiple Sclerosis Patients Taking Very High Effective Disease-Modifying Treatment. (Pubmed Central) - Mar 26, 2022
DMT was classified as moderately effective (including INFß-1a, INFß-1b, glatiramer acetate, dimethyl fumarate, teriflunomide, triamcinolone); highly effective (including fingolimod, daclizumab) and very highly effective (alemtuzumab, natalizumab, rituximab/ocrelizumab, mitoxantrone)...There was no difference in the appearance of CSF-specific oligoclonal bands (p = 0.830). Longitudinal analyses are required to confirm these results.
- |||||||||| teriflunomide / Generic mfg.
Journal: Teriflunomide shifts the astrocytic bioenergetic profile from oxidative metabolism to glycolysis and attenuates TNFα-induced inflammatory responses. (Pubmed Central) - Mar 23, 2022
Inhibition of dihydroorotate dehydrogenase via teriflunomide transiently increased both oxidative phosphorylation and glycolysis in quiescent astrocytes, but only the increased glycolytic ATP production was sustained over time, resulting in a bias away from mitochondrial ATP production even at doses down to 1 μM. Preconditioning with teriflunomide prevented the TNFα-induced skew toward oxidative phosphorylation, reduced mitochondrial ATP production, and reduced astrocytic inflammatory responses, suggesting that this drug may limit neuroinflammation by acting as a metabolomodulator.
- |||||||||| 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 23, 2022
P3, N=236, Recruiting,
Preconditioning with teriflunomide prevented the TNFα-induced skew toward oxidative phosphorylation, reduced mitochondrial ATP production, and reduced astrocytic inflammatory responses, suggesting that this drug may limit neuroinflammation by acting as a metabolomodulator. Trial completion date: Sep 2023 --> Jul 2024 | Trial primary completion date: Apr 2023 --> Apr 2024
- |||||||||| glatiramer acetate / Generic mfg., dimethyl fumarate / Generic mfg.
Clinical, Review, Journal: Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment. (Pubmed Central) - Mar 18, 2022
An increasing number of POMS patients are now treated with moderate efficacy therapies such as dimethyl fumarate and high-efficacy therapies such as natalizumab, anti-CD20 monoclonal antibodies, anti-CD52 monoclonal antibodies, and/or autologous hematopoietic stem cell transplantation...Therefore, a number of phase II and III trials are currently investigating their efficacy and safety in POMS patients. In this review, we discuss potential changes in the regulatory approval process for POMS patients that are recommended for DMTs already approved for the adult MS population, including smaller sample size for pharmacokinetic/pharmacodynamic studies, MRI-centered primary outcomes, and/or inclusion of teenagers in the adult trials.
- |||||||||| glatiramer acetate / Generic mfg., teriflunomide / Generic mfg.
Review, Journal: Vaccine Response in Patients With Multiple Sclerosis Receiving Teriflunomide. (Pubmed Central) - Mar 18, 2022
No unexpected safety signals have emerged in any vaccine study. Current guidance for patients with MS is to continue DMTs during COVID-19 vaccination, though adjusted timing of dosing for some DMTs may improve the vaccine response.
- |||||||||| dimethyl fumarate / Generic mfg., teriflunomide / Generic mfg.
Journal: A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry. (Pubmed Central) - Mar 17, 2022
There was no difference in time to first on-treatment relapse (HR = 0.78; 95% CI = 0.50-1.21), disability progression (HR = 0.55; 95% CI = 0.27-1.12) or confirmed improvement (HR = 1.17; 95% CI = 0.57-2.36). This population-based real-world study reports similarities in treatment persistence, clinical effectiveness and quality of life outcomes between teriflunomide and dimethyl fumarate.
- |||||||||| Comtan (entacapone) / Novartis, Orion Corp, Edurant (rilpivirine) / J&J
Review, Journal: Insights into the chemistry and therapeutic potential of acrylonitrile derivatives. (Pubmed Central) - Mar 17, 2022
In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Journal, Adverse events, Adverse drug reaction: Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database. (Pubmed Central) - Mar 15, 2022
All national publicly-available aggregated ADR reports recorded from 2002 to 2020 into the Reports of Adverse Reactions of Medicines (RAM) system and all complete Sicilian data reported into the Italian spontaneous reporting system (SRS) database having as suspected drugs interferon β-1a (IFN β-1a), interferon β-1b (IFN β-1b), peginterferon β-1a (PEG-IFN β-1a), glatiramer acetate (GA), natalizumab (NTZ), fingolimod (FNG), teriflunomide (TRF), dimethyl fumarate (DMF), alemtuzumab (Alem), ocrelizumab (OCZ), or cladribine (Cladr), were collected...The reporting of drugs-related ADRs in MS were mostly reported in the literature, but some unknown ADRs were also found. However, further studies are necessary to increase the awareness about the safety profiles of new drugs on the market.
|
