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.

Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants.

SAR443820 (DNL788) is a selective, orally bioavailable, brain penetrant inhibitor of receptor-interacting serine/threonine protein kinase 1 (RIPK1). This phase I first-in-human healthy participant study (NCT05795907) was comprised of three parts: randomized, double-blind, placebo-controlled single ascending dose (SAD; part 1a); 14-day multiple ascending dose (MAD; part 2) parts that evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of SAR443820; and a separate open-label, single-dose part 1b (PK-cerebrospinal fluid [CSF]) to assess SAR443820 levels in CSF. SAR443820 was well-tolerated in healthy participants, and no treatment discontinuation related to an adverse event (AE) occurred.

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.

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).

Teriflunomide real-world evidence: Global differences in the phase 4 Teri-PRO study.

Background: The demographics and management of patients with multiple sclerosis (MS) differ across geographical regions, but it is unclear whether/how these differences affect treatment outcomes. The aim of this post-hoc analysis was to assess teriflunomide use and patient-reported outcomes in the United States (US) and the rest of the world (ROW) in the phase 4 Teri-PRO study (NCT01895335).

Methods: In the phase 4, real-world, Teri-PRO study, patients with relapsing forms of MS received teriflunomide for 48 weeks according to local labeling.

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.

Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice.

Background: Patient-reported outcomes (PROs) can assist clinicians in understanding the impact of disease-modifying therapy (DMT) on the daily lives of patients with multiple sclerosis (MS). With an increased number of DMTs becoming available, patients are now switching treatments more frequently in clinical practice. The effects of switching DMTs on a patient's daily life and their disease course may be reflected in PROs.

Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study.

Background: Patient-reported outcomes (PROs) provide clinicians with further understanding of the impact of treatment on patients' daily lives. In addition, real-world studies, which employ broader inclusion criteria than randomized trials, may help to inform prescribing decisions when selecting a disease-modifying therapy (DMT) to treat relapsing forms of MS (RMS). We sought to use PROs to determine patient treatment satisfaction and other treatment outcomes, and report safety and tolerability associated with teriflunomide, in the global, phase 4 Teri-PRO study (NCT01895335).

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.

Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis.

Introduction: Teriflunomide, indicated for the treatment of relapsing-remitting multiple sclerosis, is contraindicated in pregnancy based on signs of developmental toxicity in the offspring of rats and rabbits; developmental toxicity has also been observed in preclinical studies of other disease-modifying therapies. Despite the requirement to use reliable contraception in clinical trials evaluating the safety and efficacy of teriflunomide, a number of pregnancies have been reported. This work reports pregnancy outcomes in teriflunomide clinical trials.

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.

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.

Value of 18FDG PET scan in staging of ocular adnexal lymphomas: a large single-center experience.

Fluorine 18 deoxyglucose positron emission tomography ((18)FDG PET) is widely used in staging of non-Hodgkin's lymphomas (NHL), but very few studies have focused on its role in the initial staging of patients with ocular adnexal lymphoma (OAL). The aim of this study was therefore to evaluate the role of (18)FDG PET in the diagnosis of ophthalmologic lymphoma. A retrospective review of all imaging records, including computed tomography (CT), magnetic resonance imaging (MRI), and FDG PET, was performed.

(18)F-FDG PET/CT bone/bone marrow findings in Hodgkin's lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging.

Purpose: Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow.

Desmoplastic neurotropic melanoma in a patient with trigeminal neuralgia: FDG PET/CT and MRI.

A 51-year-old man presented with a hard subcutaneous nodule adhering to the underlying bone structures of the left eyelid in 2004. Histopathology showed a desmoplastic neurotropic melanoma (DNM) with perineural invasion. Patient presented with a first recurrence in October 2005, which was treated by surgery.

Validation and limitations of use of a breast cancer nomogram predicting the likelihood of non-sentinel node involvement after positive sentinel node biopsy.

Background: Axillary lymph node dissection (ALND) for patients with positive sentinel lymph nodes (SLNs) is currently under discussion in the literature. The breast cancer nomogram (BCN), an online tool developed by the Memorial Sloan-Kettering Cancer Center (MSKCC), aims to predict the risk of positive non-SLN in SLN-positive patients. The purpose of this study was to test the accuracy of the nomogram on patients with macrometastatic and micrometastatic SLN-positive biopsy findings.

[Routine sentinel node detection in breast cancer. Experience of the Curie Institute].

Since January 2000, sentinel lymph node detection is routinely performed at the Institut Curie, involving a multidisciplinary team of trained surgeons, nuclear medicine physicians, radiologists and pathologists. During a three-year period, 738 patients undergoing tumorectomy with conservative surgical treatment of the breast were included in the sentinel node procedure consisting of systematic pre-operative tumor biopsies, peritumoral lymph tracer injections at tumor contact (radionuclide/blue dye), primary surgical removal of the first sentinel lymph node, frozen section diagnosis, followed by a standardized pathological analysis, and finally the application of precise criteria to determine whether further surgery is necessary. This article is an evaluation of the sentinel lymph node technique in a specialized Center providing a breakdown of the strong points and weak points of the procedure.