Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

Background: The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.

Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria (defined as a 24-hour urinary protein-to-creatinine ratio of ≥1 [with protein and creatinine both measured in grams]) despite optimized supportive therapy.

Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers.

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported.

Materials And Methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use.

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies.

Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team.

Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Background: Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data.

Objectives: To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS).

Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study.

Background: Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS.

Methods: Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND.

Cryptococcal Meningitis Reported With Fingolimod Treatment: Case Series.

Background And Objectives: To describe the characteristics of patients with MS reporting cryptococcal meningitis (CM) while treated with fingolimod.

Methods: The Novartis safety database was searched for cases with CM between January 26, 2006, and February 28, 2020. The reporting rate of CM was estimated based on the case reports received and exposure to fingolimod in the postmarketing setting during the relevant period.

Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.

Background: Magnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS).

Objective: To examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM).

Methods: Patients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day;  =1037) or placebo ( = 523).

COVID-19 Infection in Fingolimod- or Siponimod-Treated Patients: Case Series.

Background And Objectives: A descriptive analysis of COVID-19 infection in patients with multiple sclerosis (MS) receiving fingolimod or siponimod.

Methods: We reviewed the cases of COVID-19 from postmarketing or ongoing clinical trials reported to Novartis through December 27, 2020.

Results: As of December 27, 2020, 283 cases had been reported in fingolimod-treated patients.

Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey.

Background: A digital tool, Multiple Sclerosis Progression Discussion Tool (MSProDiscuss), was developed to facilitate discussions between health care professionals (HCPs) and patients in evaluating early, subtle signs of multiple sclerosis (MS) disease progression.

Objective: The aim of this study is to report the findings on the usability and usefulness of MSProDiscuss in a real-world clinical setting.

Methods: In this cross-sectional, web-based survey, HCPs across 34 countries completed an initial individual questionnaire (comprising 7 questions on comprehensibility, usability, and usefulness after using MSProDiscuss during each patient consultation) and a final questionnaire (comprising 13 questions on comprehensibility, usability, usefulness, and integration and adoption into clinical practice to capture the HCPs' overall experience of using the tool).

Improvement of long-term risks of cardiovascular events associated with community-based disease management in Chinese patients of the Xinjiang autonomous region of China.

Background: A recent community-based disease management (CBDM) pilot study reported a 20.5% prevalence of hypertension and a 0.5 and 3.

A Physician-Completed Digital Tool for Evaluating Disease Progression (Multiple Sclerosis Progression Discussion Tool): Validation Study.

Background: Defining the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) can be challenging and delayed. A digital tool (MSProDiscuss) was developed to facilitate physician-patient discussion in evaluating early, subtle signs of multiple sclerosis (MS) disease progression representing this transition.

Objective: This study aimed to determine cut-off values and corresponding sensitivity and specificity for predefined scoring algorithms, with or without including Expanded Disability Status Scale (EDSS) scores, to differentiate between RRMS and SPMS patients and to evaluate psychometric properties.

Slope of change in HbA from baseline with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes.

Aims: To analyse the effect of baseline glycated haemoglobin (HbA) on the reduction in HbA with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes.

Materials And Methods: Using regression analyses of individual patient data from two Phase III studies, we compared the change in HbA according to a unit change in baseline HbA (the slope) with empagliflozin 10 mg or 25 mg vs sitagliptin (monotherapy) after 24 weeks, and with empagliflozin 25 mg vs glimepiride (as add-on to metformin) after 52 weeks.

Results: Steeper slopes of HbA1c decline were observed with empagliflozin 10 or 25 mg vs sitagliptin monotherapy at week 24.

Efficacy and safety of empagliflozin in patients with type 2 diabetes from Asian countries: pooled data from four phase III trials.

We investigated the efficacy and safety of empagliflozin over 24 weeks in Asian patients with type 2 diabetes (T2DM) using pooled data from four phase III trials. In these trials, patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo as monotherapy or add-on to metformin, metformin plus sulphonylurea or pioglitazone ± metformin. In total, 1326 patients from Asia received ≥1 dose of study drug.

Treatment satisfaction in type 2 diabetes patients taking empagliflozin compared with patients taking glimepiride.

Purpose: This exploratory analysis assessed and compared patients' treatment satisfaction with empagliflozin plus metformin versus glimepiride plus metformin, using data obtained from the Diabetes Treatment Satisfaction Questionnaire, status version (DTSQs) collected in a randomized, double-blind, double-dummy clinical trial.

Methods: Observed values for DTSQs scale score and each of its eight items were summarized by visit and treatment arm. Changes from baseline in these scores were analyzed using linear mixed models for repeated measures.

Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition.

Objective: Sodium-glucose cotransporter 2 (SGLT2) inhibitors cause substantially less weight loss than expected from the energy excreted via glycosuria. Our aim was to analyze this phenomenon quantitatively.

Research Design And Methods: Eighty-six patients with type 2 diabetes (HbA1c 7.

Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study.

Background: This study evaluated the effect of empagliflozin on postprandial glucose (PPG) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods: Patients (N = 60; baseline mean [SD] HbA1c 7.91 [0.

Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes.

Objective: To investigate the long-term safety and efficacy of empagliflozin, a sodium glucose cotransporter 2 inhibitor; sitagliptin; and metformin in patients with type 2 diabetes.

Research Design And Methods: In this randomized, open-label, 78-week extension study of two 12-week, blinded, dose-finding studies of empagliflozin (monotherapy and add-on to metformin) with open-label comparators, 272 patients received 10 mg empagliflozin (166 as add-on to metformin), 275 received 25 mg empagliflozin (166 as add-on to metformin), 56 patients received metformin, and 56 patients received sitagliptin as add-on to metformin.

Results: Changes from baseline in HbA1c at week 90 were -0.

Molecular effects of C-Peptide in microvascular blood flow regulation.

C-Peptide is produced in beta-cells in the pancreas, and secreted into the blood stream in equimolar amounts with insulin. For a long time, C-peptide was considered as an important component in the biosynthesis of insulin, but otherwise believed to possess minimal biological activity. In the recent years, numerous studies demonstrated that lacking C-peptide in type 1 diabetic patients might exert an important role in the development of microvascular complications such as nephropathy or neuropathy.

C-peptide and its C-terminal fragments improve erythrocyte deformability in type 1 diabetes patients.

Aims/hypothesis: Data now indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. This study aimed to investigate the influence of C-peptide and fragments thereof on erythrocyte deformability and to elucidate the relevant signal transduction pathway.

Methods: Blood samples from 23 patients with type 1 diabetes and 15 matched healthy controls were incubated with 6.