The specific anti-hostility effect of lurasidone in patients with an acute exacerbation of schizophrenia: results of pooled post hoc analyses in adolescents and adults.

Symptoms of hostility in patients during acute exacerbations of schizophrenia have been associated with aggressive behavior. Data suggest that some second-generation antipsychotics have specific anti-hostility effects, independent of sedation and positive symptom improvement. Two post hoc analyses were performed to examine the efficacy of lurasidone for reducing hostility in patients with schizophrenia.

Mapping analysis to predict SF-6D utilities from health outcomes in people with focal epilepsy.

Background: Focal-onset seizures (FOS) are commonly experienced by people with epilepsy and have a significant impact on quality of life (QoL). This study aimed to develop a mapping algorithm to predict SF-6D values in adults with FOS for use in economic evaluations of a new treatment, cenobamate.

Methods: An online survey, including questions on disease history, SF-36, and an epilepsy-specific measure (QOLIE-31-P) was administered to people with FOS in the UK, France, Italy, Germany, and Spain.

A pilot open-label study of aldose reductase inhibition with AT-001 (caficrestat) in patients hospitalized for COVID-19 infection: Results from a registry-based matched-control analysis.

Background And Aims: Cardiometabolic disease may confer increased risk of adverse outcomes in COVID-19 patients by activation of the aldose reductase pathway. We hypothesized that aldose reductase inhibition with AT-001 might reduce viral inflammation and risk of adverse outcomes in diabetic patients with COVID-19.

Methods: We conducted an open-label prospective phase 2 clinical trial to assess safety, tolerability and efficacy of AT-001 in patients hospitalized with COVID-19 infection, history of diabetes mellitus and chronic heart disease.

Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years.

Background: Few data exist concerning conversion to secondary progressive MS in patients treated with disease-modifying therapies.

Objective: Determine the proportion of alemtuzumab-treated patients converting from relapsing-remitting to secondary progressive MS during the CARE-MS core and extension studies.

Methods: Patients ( = 811) were analyzed post hoc for secondary progressive MS conversion.

Subcutaneous Sarilumab in Patients With Rheumatoid Arthritis who Previously Received Subcutaneous Sarilumab or Intravenous Tocilizumab: An Open-Label Extension of a Randomized Clinical Trial.

Objective: This post hoc analysis evaluated the safety and efficacy of open-label sarilumab in patients with rheumatoid arthritis (RA) who completed the phase III double-blind ASCERTAIN study (NCT01768572) and switched from intravenous (IV) tocilizumab to subcutaneous (SC) sarilumab, or who continued SC sarilumab in the open-label extension (OLE) study EXTEND (NCT01146652).

Methods: Patients who completed ASCERTAIN were eligible to enroll in EXTEND to receive sarilumab 200 mg SC every 2 weeks (Q2W). Safety and efficacy were reported through 96 weeks in the OLE in patients who switched from tocilizumab IV to sarilumab 200 mg SC Q2W, who switched from sarilumab 150 mg SC Q2W to sarilumab 200 mg SC Q2W, or who continued sarilumab 200 mg SC Q2W.

Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials.

Background: Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes.

Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies.

Background: Alemtuzumab is administered as two annual courses for relapsing-remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen.

Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers).

Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension.

Objective: Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).

Methods: During the 48-week OLE, patients received sarilumab 200 mg subcutaneously once every 2 weeks. Safety (March 2017 cut-off) and efficacy, including patient-reported outcomes, were evaluated.

Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma.

Background: Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline.

Objective: We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk.

Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials.

Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week.

Comparative effectiveness of teriflunomide and dimethyl fumarate in patients with relapsing forms of MS in the retrospective real-world Teri-RADAR study.

Aim: Head-to-head clinical trials of teriflunomide (TFM) versus dimethyl fumarate (DMF) have not been conducted.

Objectives: To compare the real-world effectiveness of TFM versus DMF.

Methods: Anonymized data were collected from patients with relapsing multiple sclerosis (MS) initiating treatment with teriflunomide (N = 50) or DMF (N = 50).

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.

Clinical efficacy of teriflunomide over a fixed 2-year duration in the TOWER study.

Patients enrolled in the phase 3 TOWER study (NCT00751881) of teriflunomide had variable treatment durations (48-173 weeks). This has led to challenges when interpreting results in the context of other phase 3 trials of disease-modifying therapies for multiple sclerosis, which typically have a fixed 2-year duration. This communication reports clinical outcomes in TOWER over a fixed 2-year period.

Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.

Objective: To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.

Methods: In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity.

Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy.

Objective: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).

Methods: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.

Teriflunomide slows BVL in relapsing MS: A reanalysis of the TEMSO MRI data set using SIENA.

Objective: To assess, using structural image evaluation using normalization of atrophy (SIENA), the effect of teriflunomide, a once-daily oral immunomodulator, on brain volume loss (BVL) in patients with relapsing forms of MS enrolled in the phase 3 TEMSO study.

Methods: TEMSO MR scans were analyzed (study personnel masked to treatment allocation) using SIENA to assess brain volume changes between baseline and years 1 and 2 in patients treated with placebo or teriflunomide. Treatment group comparisons were made via rank analysis of covariance.

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.

Comparing outcomes from clinical studies of oral disease-modifying therapies (dimethyl fumarate, fingolimod, and teriflunomide) in relapsing MS: Assessing absolute differences using a number needed to treat analysis.

Dimethyl fumarate (DMF), fingolimod, and teriflunomide are oral disease-modifying therapies (DMTs) indicated for the treatment of relapsing-remitting multiple sclerosis. Despite well-established limitations of cross-trial comparisons, DMTs are still frequently compared in terms of relative reductions in specific endpoints, most commonly annualized relapse rate. Consideration of absolute risk reduction and number needed to treat (NNT) provides an alternative approach to assess the magnitude of treatment effect and can provide valuable additional information on therapeutic gain.

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.

Effects of chemotherapy on the cytogenetic constitution of Wilms' tumor.

The management of Wilms' tumors consists of a combination of surgery, chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk stratified according to histologic subtype and stage. Although the cytogenetic characteristics of Wilms' tumors are well established, the cytogenetic effects related to chemotherapy are widely unknown.