Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study—Joint and Skin (BeRLiSS-JS)

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up

Four- and 5-Year-Olds Infer Differences in Relative Ability and Appropriately Allocate Roles to Achieve Cooperative, Competitive, and Prosocial Goals

Preschoolers are sensitive to differences in individuals’ access to external resources (e.g., tools) in division of labor tasks. However, little is known about whether children consider differences in individuals’ internal resources (e.g., abilities) and whether children can flexibly allocate roles across different goal contexts. Critically, factors that are relevant to role allocation in collaborative contexts may be irrelevant in competitive and prosocial ones. In three preregistered experiments, we found that 4- and 5-year-olds (mean: 54 months; range: 42–66 months; N = 132) used age differences to infer relative ability and appropriately allocate the harder and easier of two tasks in a dyadic cooperative interaction (Experiment 1), and appropriately ignored relative ability in competitive (Experiment 2) and prosocial (Experiment 3) contexts, instead assigning others the harder and easier roles, respectively. Thus, 3-and-a-half- to 5-year-olds evaluate their own abilities relative to others and effectively allocate roles to achieve diverse goals. </jats:p

Preschoolers appropriately allocate roles based on relative ability in acooperative interaction

In cooperative activities, all parties have a shared goalbut may not have the same set of skills. The currentstudy considers whether preschoolers are sensitive toprobable differences in individuals’ competence whenallocating roles. We found that 3.5- to 5.5-year-olds userelative competence, as indexed by the age of theirintended partner, to determine who should do the harderand easier of two tasks in a cooperative interaction. Asecond experiment demonstrated that children allocateroles differently in a competitive context. Youngchildren infer differences in others’ ability and candivide labor efficiently to achieve their goals

A COMPARATIVE-ANALYSIS OF THE URINARY-EXCRETION PROFILES OF MESNA AND ARGIMESNA FOLLOWING ORAL-ADMINISTRATION TO HEALTHY-VOLUNTEERS

Mesna, the sodium salt of 2-mercaptoethanesulphonic acid (MES), is a uroprotective agent used to prevent oxazaphosphorine-induced haemorrhagic cystitis during cancer chemotherapy. Oral administration of mesna is frequently associated with nausea and vomiting secondary to its unpleasant taste. Argimesna, a newly synthesised salt of MES in which sodium is replaced by arginine, has not been associated with similar adverse effects. In this study, the urinary excretion of the two salts of MES was compared after oral administration of either mesna 800mg or argimesna 1800mg (equivalent to 920mg of mesna). The 2 drugs exhibited almost identical urinary excretion patterns. Percentage recoveries 12 hours after drug administration were 14.8 and 13.2% of the dose for mesna and argimesna, respectively. Maximum urinary concentrations of free thiols were observed with both drugs during the 0- to 4-hour urine collection, and were 3.9 mmol/L for mesna and 3.3 mmol/L for argimesna. Since 0.61 mmol/L is considered the minimum free thiol concentration required to confer uroprotection, it is concluded that argimesna ensures a uroprotective activity equivalent to that of mesna and may be advantageously substituted for mesna in oral therapeutic regimens

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies—except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended—CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease

Belimumab: a step forward in the treatment of systemic lupus erythematosus

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic B cell-mediated autoimmune disease which can potentially involve several organs and systems. The development of SLE is associated with a complexity of genetic, hormonal and environmental factors leading to immune deregulation and production of autoantibodies. Therefore, novel therapies have focused on B cells as key effectors of SLE pathogenesis. Belimumab is a fully humanized monoclonal antibody that antagonizes B-lymphocyte stimulator (BLyS); it is the first and the only biological drug approved for SLE in over 50\ua0years. Areas covered: In this review we discuss the pharmacological properties of belimumab, new recommendations for its use in clinical practice and its evidence of efficacy and safety based on clinical trial and real-life data. Expert opinion: Efficacy and safety of belimumab in clinical practice have been well established. To date, it is known that early introduction of belimumab in SLE can maximize the efficacy of the drug. A number of questions are still open, such as the timing of belimumab discontinuation and its possible association with other biological drugs, which need to be assessed in future studies