BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
- MeSH
- antidepresiva škodlivé účinky MeSH
- indany * MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu * škodlivé účinky MeSH
- lidé MeSH
- oxadiazoly * MeSH
- roztroušená skleróza * chemicky indukované MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- serotonin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis. METHODS: EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated). FINDINGS: The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly in the first 12 weeks (55 [5·0%] vs nine [<1%]). Three people who received evobrutinib and one who received teriflunomide met the biochemical definition of Hy's law; all cases resolved after discontinuation of treatment. There were two deaths (one in each group), neither related to study treatment. INTERPRETATION: The efficacy of evobrutinib was not superior to that of teriflunomide. Together, efficacy and liver-related safety findings do not support the use of evobrutinib in people with relapsing multiple sclerosis. FUNDING: Merck.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hydroxybutyráty * MeSH
- inhibitory proteinkinas terapeutické užití škodlivé účinky MeSH
- krotonáty * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nitrily * terapeutické užití MeSH
- piperidiny MeSH
- proteinkinasa BTK antagonisté a inhibitory MeSH
- pyrimidiny * terapeutické užití MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie MeSH
- toluidiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Disease-modifying therapies for relapsing multiple sclerosis reduce relapse rates by suppressing peripheral immune cells but have limited efficacy in progressive forms of the disease where cells in the central nervous system play a critical role. 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.
OBJECTIVE: To investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK. METHODS: DAYBREAK (ClinicalTrials.gov-NCT02576717), an open-label extension study of oral ozanimod 0.92 mg, enrolled participants aged 18-55 years with RMS who completed phase 1-3 ozanimod trials. Participants who were fully vaccinated against SARS-CoV-2 with mRNA or non-mRNA vaccines, were unvaccinated, and/or had COVID-19-related adverse events (AEs, with or without vaccination) and postvaccination serum samples were included (n = 288). Spike receptor binding domain (RBD) antibody levels (seroconversion: ≥0.8 U/mL) and serologic evidence of SARS-CoV-2 infection (nucleocapsid IgG: ≥1 U/mL) were assessed (Roche Elecsys/Cobas e411 platform). RESULTS: In fully vaccinated participants (n = 148), spike RBD antibody seroconversion occurred in 90% (n = 98/109) of those without serologic evidence of prior SARS-CoV-2 exposure (100% [n = 80/80] seroconversion after mRNA vaccination) and in 100% (n = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID-19-related AEs were reported in 10% (n = 15/148) of fully vaccinated participants-all were nonserious and not severe; all participants recovered. INTERPRETATION: Most ozanimod-treated participants with RMS mounted a serologic response to SARS-CoV-2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID-19-related AEs post-full vaccination in participants taking ozanimod were nonserious and not severe.
BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × μg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 μg/mL (ratio 1.00)). B-cell counts (median cells/μL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.
- MeSH
- humanizované monoklonální protilátky škodlivé účinky MeSH
- injekce subkutánní MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- roztroušená skleróza * chemicky indukované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. OBJECTIVE: To characterize long-term safety and efficacy of ozanimod. METHODS: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. RESULTS: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. CONCLUSIONS: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.
PURPOSE OF REVIEW: As of January 21st 2022, over 340 million are confirmed cases of coronavirus disease 2019 (COVID-19), including nearly 5.6 million deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is neurotropic and affects the neural parenchyma through direct viral invasion from the nasal mucosa and postinfectious cytokine storm. Further challenges of SARS-CoV-2 infection are nowadays linked to variants of concern. Multiple sclerosis is an inflammatory and progressive degenerative disorder of the central nervous system commonly affecting young adults and potentially generating irreversible disability. Since the beginning of the SARS-CoV-2 pandemic, people with multiple sclerosis (pwMS) have been considered 'extra' vulnerable because of the immune-mediated nature of the disease, the disability status, and the immunomodulatory therapies potentially increasing the risk for viral infection. Today multiple sclerosis neurologists are faced with several challenges in the management of pwMS to both prevent SARS-CoV-2 infection and protection from disease worsening. We aimed to highlight today's most relevant facts about the complex management of pwMS in the COVID-19 era. RECENT FINDINGS: The incidence of COVID-19 among pwMS does not differ from the general population. The prognosis of COVID-19 among pwMS is driven by older age, male sex, nonambulatory status, comorbidity as in the general population, as well as by corticosteroid treatment and B-cell depleting agents which decrease seropositivity from SARS-CoV-2 infection and immune responses to SARS-CoV-2 vaccination. SUMMARY: Disease modifying treatments (DMTs) should be regularly continued in relation to SARS-CoV-2 vaccination, but an ad hoc timing is required with B-cell depleting agents. SARS-CoV-2 vaccination is recommended in pwMS with willingness improving through health education programs. Multiple sclerosis does not seem to worsen after SARS-Cov2 vaccination but COVID-19 may enhance disease activity.
- MeSH
- COVID-19 * prevence a kontrola MeSH
- lidé MeSH
- mladý dospělý MeSH
- progrese nemoci MeSH
- RNA virová MeSH
- roztroušená skleróza * epidemiologie MeSH
- SARS-CoV-2 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis. METHODS: We did a 16-week, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centres (academic sites, specialty clinics, and general neurology centres) in ten countries in Europe and North America. Eligible participants were adults aged 18-55 years with diagnosed relapsing multiple sclerosis (either relapsing-remitting or relapsing secondary progressive multiple sclerosis), and one or more of the following criteria: at least one relapse within the previous year, at least two relapses within the previous 2 years, or at least one active gadolinium-enhancing brain lesion in the 6 months before screening. Exclusion criteria included a diagnosis of primary progressive multiple sclerosis or a diagnosis of secondary progressive multiple sclerosis without relapse. We used a two-step randomisation process to randomly assign eligible participants (1:1) to two cohorts, then further randomly assign participants in each cohort (1:1:1:1) to four tolebrutinib dose groups (5, 15, 30, and 60 mg administered once daily as an oral tablet). Cohort 1 received tolebrutinib for 12 weeks, then matched placebo (ie, identical looking tablets) for 4 weeks; cohort 2 received 4 weeks of placebo followed by 12 weeks of tolebrutinib. Participants and investigators were masked for dose and tolebrutinib-placebo administration sequence; investigators, study team members, and study participants did not have access to unmasked data. MRI scans were done at screening and every 4 weeks over 16 weeks. The primary efficacy endpoint was the number of new gadolinium-enhancing lesions detected on the scan done after 12 weeks of tolebrutinib treatment (assessed at week 12 for cohort 1 and week 16 for cohort 2), relative to the scan done 4 weeks previously, and compared with the lesions accumulated during 4 weeks of placebo run-in period in cohort 2. Efficacy data were analysed in a modified intention-to-treat population, using a two-step multiple comparison procedure with modelling analysis. Safety was assessed for all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03889639), EudraCT (2018-003927-12), and WHO (U1111-1220-0572), and has been completed. FINDINGS: Between May 14, 2019, and Jan 2, 2020, we enrolled and randomly assigned 130 participants to tolebrutinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg, and 32 to 60 mg. 129 (99%) completed the treatment regimen and 126 were included in the primary analysis. At treatment week 12, there was a dose-dependent reduction in the number of new gadolinium-enhancing lesions (mean [SD] lesions per patient: placebo, 1·03 [2·50]; 5 mg, 1·39 [3·20]; 15 mg, 0·77 [1·48]; 30 mg, 0·76 [3·31]; 60 mg, 0·13 [0·43]; p=0·03). One serious adverse event was reported (one patient in the 60 mg group was admitted to hospital because of a multiple sclerosis relapse). The most common non-serious adverse event during tolebrutinib treatment was headache (in one [3%] of 33 in the 5 mg group; three [9%] of 32 in the 15 mg group; one [3%] of 33 in the 30 mg group; and four [13%] of 32 in the 60 mg group). No safety-related discontinuations or treatment-related deaths occurred. INTERPRETATION: 12 weeks of tolebrutinib treatment led to a dose-dependent reduction in new gadolinium-enhancing lesions, the 60 mg dose being the most efficacious, and the drug was well tolerated. Reduction of acute inflammation, combined with the potential to modulate the immune response within the CNS, provides a scientific rationale to pursue phase 3 clinical trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis. FUNDING: Sanofi.
- MeSH
- centrální nervový systém diagnostické zobrazování účinky léků imunologie patologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- hodnocení výsledků zdravotní péče * MeSH
- inhibitory proteinkinas aplikace a dávkování škodlivé účinky farmakokinetika farmakologie MeSH
- klinické křížové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- proteinkinasa BTK antagonisté a inhibitory MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza diagnostické zobrazování farmakoterapie imunologie patologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zánět diagnostické zobrazování farmakoterapie imunologie patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data. METHODS: We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data. RESULTS: At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE. CONCLUSIONS: Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.
- MeSH
- indany MeSH
- lidé MeSH
- oxadiazoly MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie epidemiologie MeSH
- roztroušená skleróza * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ozanimod is a sphingosine 1-phosphate receptor modulator, which selectively binds to sphingosine 1-phosphate receptor subtypes 1 and 5 with high affinity. In the RADIANCE phase 2 study in participants with relapsing multiple sclerosis, ozanimod was associated with better efficacy than placebo on MRI measures and was well tolerated. The RADIANCE phase 3 study aimed to confirm the safety and efficacy of ozanimod versus interferon beta-1a in individuals with relapsing multiple sclerosis. METHODS: We did a 24-month, multicentre, double-blind, double-dummy phase 3 trial in participants with relapsing multiple sclerosis at 147 medical centres and clinical practices in 21 countries. Participants were aged 18-55 years, had multiple sclerosis according to 2010 McDonald criteria, a relapsing clinical course, brain MRI lesions consistent with multiple sclerosis, an expanded disability status scale score of 0·0-5·0, and either at least one relapse within 12 months before screening or at least one relapse within 24 months before screening plus at least one gadolinium-enhancing lesion within the 12 months before randomisation. Participants were randomly assigned (1:1:1) via an interactive voice response system to daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment allocation. The primary endpoint was annualised relapse rate (ARR) over 24 months. The primary analysis was done in the intention-to-treat population of all participants who received study drug and safety was assessed in all randomly assigned participants who received study drug, grouped by highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, NCT02047734, and EudraCT, 2012-002714-40. FINDINGS: Between Dec 27, 2013, and March 31, 2015, we screened 1695 participants, of which 375 did not meet inclusion criteria. 1320 participants were enrolled and randomly assigned to a group, of whom 1313 received study drug (433 assigned to ozanimod 1·0 mg, 439 assigned to ozanimod 0·5 mg, and 441 assigned to interferon beta-1a) and 1138 (86·7%) completed 24 months of treatment. Adjusted ARRs were 0·17 (95% CI 0·14-0·21) with ozanimod 1·0 mg, 0·22 (0·18-0·26) with ozanimod 0·5 mg, and 0·28 (0·23-0·32) with interferon beta-1a, with rate ratios versus interferon beta-1a of 0·62 (95% CI 0·51-0·77; p<0·0001) for ozanimod 1·0 mg and 0·79 (0·65 to 0·96; p=0·0167) for ozanimod 0·5 mg. The incidence of treatment-emergent adverse events was higher in the interferon beta-1a group (365 [83·0%] of 440 participants) than in the ozanimod 1·0 mg group (324 [74·7%] of 434) or the ozanimod 0·5 mg group (326 [74·3%] of 439). More participants in the interferon beta-1a group had treatment-emergent adverse events leading to treatment discontinuation than in the ozanimod groups. Incidences of infections and serious treatment-emergent adverse events were similar across treatment groups. No cases of ozanimod-related symptomatic reduction in heart rate and no second-degree or third-degree cases of atrioventricular block were reported. INTERPRETATION: In this 24-month phase 3 study in participants with relapsing multiple sclerosis, ozanimod was well tolerated and associated with a significantly lower rate of clinical relapses than intramuscular interferon beta-1a. These findings show the potential of ozanimod as an effective oral therapy for individuals with relapsing multiple sclerosis. FUNDING: Celgene International II.
- MeSH
- bradykardie chemicky indukované MeSH
- dospělí MeSH
- imunosupresiva škodlivé účinky terapeutické užití MeSH
- indany aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- infekce etiologie MeSH
- interferon beta 1a škodlivé účinky terapeutické užití MeSH
- lékové postižení jater etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek patologie MeSH
- následné studie MeSH
- neurozobrazování MeSH
- oxadiazoly aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- progrese nemoci MeSH
- receptory sfingosin-1-fosfátu antagonisté a inhibitory MeSH
- relabující-remitující roztroušená skleróza farmakoterapie patologie MeSH
- šedá hmota patologie MeSH
- stupeň závažnosti nemoci MeSH
- velikost orgánu MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
