Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis.

Introduction: Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing-remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb.

Methods: Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab.

Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS.

Background: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide.

Objective: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension.

Methods: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks.

Inhibition of CD40L with Frexalimab in Multiple Sclerosis.

Background: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.

Methods: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment.

Plasma neurofilament light chain in children with relapsing MS receiving teriflunomide or placebo: A post hoc analysis of the randomized TERIKIDS trial.

Background: The phase 3 TERIKIDS study demonstrated efficacy and manageable safety for teriflunomide versus placebo in children with relapsing multiple sclerosis (RMS).

Objective: Evaluate plasma neurofilament light chain (pNfL) concentrations in TERIKIDS.

Methods: Patients received placebo or teriflunomide (14 mg adult equivalent) for up to 96 weeks in the double-blind (DB) period.

Vaccine Response in Patients With Multiple Sclerosis Receiving Teriflunomide.

Many patients with multiple sclerosis (MS) receive disease-modifying therapies (DMTs), such as teriflunomide, to reduce disease activity and slow progression. DMTs mediate their efficacy by modulating or suppressing the immune system, which might affect a patient's response to vaccination. As vaccines against the SARS-CoV-2 virus become available, questions have arisen around their efficacy and safety for patients with MS who are receiving DMTs.

Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial.

Background: Therapeutic options for children with multiple sclerosis are scarce. Teriflunomide is approved in more than 80 countries for the treatment of adults with relapsing multiple sclerosis. The TERIKIDS study examined the safety and efficacy of teriflunomide in children with relapsing multiple sclerosis.

Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study.

Background: In the phase 3 TOWER core study (NCT00751881), the efficacy and safety of teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported.

Methods: All patients who entered the extension (N = 751) were assigned to teriflunomide 14 mg and assessed for long-term safety and efficacy.

Pregnancy outcomes in patients treated with leflunomide, the parent compound of the multiple sclerosis drug teriflunomide.

Leflunomide is contraindicated in pregnant women, yet human data from leflunomide-exposed pregnancies do not indicate an embryofetal toxicity signal. The objective of the present analysis was to report pregnancy outcomes for leflunomide-exposed pregnancies in clinical trials and in the post-marketing setting. Pregnancy outcomes are summarized from leflunomide clinical trials and the post-marketing setting.

Long-term outcomes with teriflunomide in patients with clinically isolated syndrome: Results of the TOPIC extension study.

Background: In the phase 3 TOPIC study, teriflunomide significantly reduced the risk of relapse determining conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome, versus placebo. We assessed clinical and safety outcomes associated with extended teriflunomide treatment in the TOPIC extension study.

Methods: Patients who completed the TOPIC core study (including those still on study at early termination) or converted to CDMS after at least 24 weeks in the core study were eligible to participate in the extension.

Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: Pooled analysis of clinical trials.

Background: In Phase 3 studies, teriflunomide reduced relapse rates and disability progression compared with placebo; however, decreases in lymphocyte counts were also observed.

Objective: To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates among patients in pooled analyses of Phase 3 core and extension studies.

Methods: Four randomized trials (TEMSO, TOWER, TENERE, and TOPIC) compared teriflunomide 7 mg or 14 mg treatment with either placebo and/or subcutaneous interferon (IFN) β-1a 44 µg in patients with relapsing forms of multiple sclerosis (MS) (or first clinical episode suggestive of MS in TOPIC).

Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience.

Background: Teriflunomide is contraindicated in pregnancy. Some pregnancies have occurred despite guidance to use effective contraception.

Objectives: To report outcomes of pregnancies occurring in teriflunomide clinical trials and the post-marketing setting.

Efficacy and safety of teriflunomide in Asian patients with relapsing forms of multiple sclerosis: A subgroup analysis of the phase 3 TOWER study.

In the phase 3 TOWER (NCT00751881) study, teriflunomide 14 mg significantly reduced annualized relapse rate (ARR) and risk of 12-week confirmed disability worsening (12-w CDW) vs placebo in patients with relapsing forms of MS (RMS). The TOWER population included an appreciable proportion of Asian patients. Reductions in ARR and 12-w CDW associated with teriflunomide 14 mg were comparable between the Asian and overall populations, as were the rates for adverse events and serious adverse events, with no new or unexpected safety findings.

Predicting long-term disability outcomes in patients with MS treated with teriflunomide in TEMSO.

Objective: To predict long-term disability outcomes in TEMSO core (NCT00134563) and extension (NCT00803049) studies in patients with relapsing forms of MS treated with teriflunomide.

Methods: A post hoc analysis was conducted in a subgroup of patients who received teriflunomide in the core study, had MRI and clinical relapse assessments at months 12 (n = 552) and 18, and entered the extension. Patients were allocated risk scores for disability worsening (DW) after 1 year of teriflunomide treatment: 0 = low risk; 1 = intermediate risk; and 2-3 = high risk, based on the occurrence of relapses (0 to ≥2) and/or active (new and enlarging) T-weighted (Tw) lesions (≤3 or >3) after the 1-year MRI.

The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies.

Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting multiple sclerosis (MS). The objective of this post hoc analysis of the phase 3, pooled TEMSO (NCT00134563) and TOWER (NCT00751881) dataset is to evaluate the effect of teriflunomide treatment on annualised relapse rate and disability worsening across patient subgroups defined according to prior disease-modifying therapy exposure. This analysis provides further supportive evidence for a consistent effect of teriflunomide across a broad range of patients with relapsing MS, including patients who have used and discontinued other disease-modifying therapies.

Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study.

Objective: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563).

Methods: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg.

Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions.

Background: Teriflunomide, a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis, has demonstrated consistent efficacy on clinical and MRI parameters in clinical trials.

Objective: To summarize the safety and tolerability profile of teriflunomide based on data from four placebo-controlled trials.

Methods: Safety and tolerability were assessed using two teriflunomide clinical program data pools.

Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens.

Objective: To evaluate immune responses to neoantigen and recall antigens in healthy subjects treated with teriflunomide.

Methods: This was a randomized, double-blind, placebo-controlled study. Subjects received oral teriflunomide (70 mg once daily for 5 days followed by 14 mg once daily for 25 days) or placebo for 30 days.

Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. We aimed to assess the efficacy and safety of teriflunomide in patients with a first clinical episode suggestive of multiple sclerosis.

Methods: In this randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 18-55 years with clinically isolated syndrome (defined as a neurological event consistent with demyelination, starting within 90 days of randomisation, and two or more T2-weighted MRI lesions ≥3 mm in diameter) from 112 centres (mostly hospitals) in 20 countries.

Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing or relapsing-remitting multiple sclerosis. We aimed to provide further evidence for the safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis.

Methods: This international, randomised, double-blind, placebo-controlled, phase 3 study enrolled adults aged 18-55 years with relapsing multiple sclerosis, one or more relapse in the previous 12 months or two or more in the previous 24 months but no relapse in the previous 30 days, and an Expanded Disability Status Scale (EDSS) score of 5.

Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial.

Background: In previous studies, teriflunomide significantly reduced the annualised relapse rate (ARR) and disability progression.

Objective: This phase 3, rater-blinded study (NCT00883337) compared teriflunomide with interferon-beta-1a (IFNβ-1a).

Methods: Patients with relapsing multiple sclerosis were randomised (1:1:1) to oral teriflunomide 7-or 14 mg, or subcutaneous IFNβ-1a 44 µg.

Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis.

Objective: To investigate the effect of teriflunomide on the efficacy and safety of seasonal influenza vaccine.

Methods: The 2011/2012 seasonal influenza vaccine (containing H1N1, H3N2, and B strains) was administered to patients with relapsing forms of multiple sclerosis (RMS) treated for ≥6 months with teriflunomide 7 mg (n = 41) or 14 mg (n = 41), or interferon-β-1 (IFN-β-1; n = 46). The primary endpoint was the proportion of patients with influenza strain-specific antibody titers ≥40, 28 days postvaccination.

Magnetic resonance imaging outcomes from a phase III trial of teriflunomide.

Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI).

Methods: Patients (n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks.

Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis.

Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients.

Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups.

Methods: RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks.

Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years.

Background: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study.

Methods: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day.

Randomized trial of oral teriflunomide for relapsing multiple sclerosis.

Background: Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis.

Methods: We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years.