Safety of Ixekizumab in Adult Patients with Moderate-to-Severe Psoriasis: Data from 17 Clinical Trials with Over 18,000 Patient-Years of Exposure.

INTRODUCTION: We report a comprehensive summary of the safety outcomes in adult patients with moderate-to-severe psoriasis with up to 5 years of exposure to ixekizumab. METHODS: Long-term safety of the IL-17A antagonist ixekizumab was assessed from 17 randomized trials. Treatment-emergent adverse events (TEAEs)-adjusted incidence rates (IRs) per 100 patient-years (PY) within 1-year time periods through 19 March 2021 were calculated for all patients treated with at least one dose of ixekizumab. Reported cases of major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) were adjudicated. RESULTS: A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and serious adverse events (AEs) were 32.5 and 5.4. IR of discontinuation because of AE was 2.9. A total of 36 deaths were reported. IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis (TB). IR of Candida infections (IR 1.9) was low; most cases of Candida were localized, and no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity were 5.9 and 5.6, respectively. No confirmed cases of anaphylaxis were observed. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). IBD events were uncommon, although a total of 31 patients (IR 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time. CONCLUSIONS: The long-term safety profile for ixekizumab is consistent with that previously reported in patients with psoriasis. No new or unexpected safety events were detected.

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

INTRODUCTION: Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. METHODS: Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh. RESULTS: Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was - 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC0-tlast, AUC0-∞, and Cmax between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable. CONCLUSION: Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation. TRAIL REGISTRATION: ClinicalTrials.gov identifier NCT03848403, NCT04259346.

Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure.

OBJECTIVES: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A (IL-17A), has shown significant efficacy in the treatment of psoriatic arthritis (PsA) and sustained long-term clinical response without unexpected new safety outcome for an IL-17A inhibitor. Here, we report the updated safety profile of ixekizumab up to 3 years in patients with PsA. METHODS: This is an integrated safety analysis from four clinical trials in patients with PsA who received at least one dose of ixekizumab. Treatment-emergent adverse events (TEAEs) and selected adverse events (AEs) exposure-adjusted incidence rates (EAIRs) per 100 patient-years up to 3 years of exposure are reported. RESULTS: A total of 1401 patients with a cumulative ixekizumab exposure of 2247.7 patient-years were included in this analysis. The EAIR of patients with ≥1 TEAE was 50.3 per 100 patient-years and most TEAEs were mild to moderate in severity. Serious AEs were reported by 134 patients (EAIR=6.0). The most reported TEAEs were nasopharyngitis (EAIR=9.0) and upper respiratory tract infection (EAIR=8.3). Infections in general and injection site reactions were the most common TEAEs; the incidence rates of serious cases were low (EAIR ≤1.2). The EAIRs of malignancies (EAIR=0.7), inflammatory bowel disease (EAIR=0.1) including ulcerative colitis and Crohn's disease, depression (EAIR=1.6), and major adverse cerebro-cardiovascular events (EAIR=0.5) were low. As assessed, based on year of exposure, incidence rates were decreasing or constant over time. CONCLUSIONS: In this analysis, the overall safety profile and tolerability of ixekizumab are consistent with the known safety profile in patients with PsA. No new or unexpected safety events were detected. TRIAL REGISTRATION NUMBER: NCT01695239, NCT02349295, NCT02584855, NCT03151551.

Maternal sensitivity in interactions with their 2-month-old infants in Rio de Janeiro - Brazil.

This paper reports on a study of maternal sensitivity in 22 primiparous women and their infants from Rio de Janeiro, Brazil. A semi-structured interview was conducted about sociodemographic risk, as and videotaped home observations to assess maternal sensitivity, and its relation with warmth, verbal and physical engagement, and camera awareness. A K-means cluster analysis was performed to examine patterns of risk in relation to maternal sensitivity. Compared to the 15 mothers with higher sensitivity scores, the seven mothers with lower sensitivity scores were characterized by lower educational levels, lower income, lower age, living in a slum, unplanned and unwanted pregnancies, and later onset of prenatal care. Whether father was resident did not appear to distinguish between the lower and higher sensitivity groups. The pattern of social-contextual risk for Brazilian mothers showing less sensitive caregiving to their infants provide a clear direction for future research in this cultural context.

Maternal sensitivity in mother-infant interactions in Rio de Janeiro - Brazil.

This article reports on a study of maternal sensitivity in 22 primiparous women and their infants from Rio de Janeiro, Brazil. Two semi-structured interviews were conducted, as well as videotaped naturalistic home observations of the dyads. A K-means cluster analysis was performed to examine patterns of risk in relation to maternal sensitivity. The results reveal that compared to the 15 mothers with higher sensitivity scores, the 7 mothers with lower sensitivity scores were characterized by lower educational levels, lower income, lower age, living in a slum, unplanned and unwanted pregnancies, and later onset of prenatal care. Whether father was resident did not appear to distinguish between the lower and higher sensitivity groups. The article concludes that the patterns of social-contextual risk for Brazilian mothers showing less sensitive caregiving to their infants provide a clear direction for future research in this cultural context.

Asma - aspectps clínico-epidemiológicos de 237 pacientes de um ambulatório pediátrico especializado / Asthma - Clinical and epidemiological aspects of 237 ooutpatients in a specialized pediatric unit

Objetivo: Os autores analisam e descrevem as características clínico-epidemiológicas de pacientes com diagnósticos de asma em um ambulatório pediátrico especializado. Métodos: Pacientes asmáticos em seguimento na Unidade de Alergia e Imunologia do Departamento de Pediatria (Universidade de Säo Paulo) no período de 1988 a 1995 foram avaliados aleatória e retrospectivamente. Foram submetidos a um protocolo para doenças associadas (refluxo gastroesofágico, toxocaríase, tuberculose, imunoodeficiências e outras doenças atópicas). A gravidade da asma foi classificada de acordo com o I Consenso Brasileiro para o Manejo da Asma. Resultados: 237 pacientes (128M:109F) foram incluídos, e a média de idade foi de 86 meses. O primeiro episódio de sibilância ocorreu, em 56 por cento dos casos, durante o primeiro ano de vida. Antecendentes familiares de atopia foram relatados em 61,6 por cento dos pacientes. Ocorreu mudança na classificaçäo da gravidade da asma, com reduçäo de 53 por cento para 35 por cento dos casos considerados graves entre sua admissäo e o preenchimento do protocolo de avaliaçäo. Os fatores desencadeantes mais relatados foram: alteraçöes climáticas (78,3 por cento) e poeira (64,7 por cento). Os diagnósticos associados foram: refluxo-gastro-esofágico (n=57), toxocaríase (n=17), tuberculose (n=7) e imunodeficiências(n=16). Outras doenças atópicas estavam associadas em 90,2 por cento dos casos...