A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.

BACKGROUND: Obesity is one of the critical public health problems in our society. It leads to various health conditions, such as type 2 diabetes mellitus, cardiovascular disease, hypertension, dyslipidaemia, and non-alcoholic fatty liver disease. With the rising incidence of obesity, there is a growing demand for new therapies which can effectively manage body weight and improve health. CURRENT EVIDENCE: Currently under development, multi-receptor agonist drugs may offer a promising solution to meet this unmet medical need. Retatrutide is a novel triple receptor agonist peptide that targets the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). This novel drug has the potential to treat metabolic abnormalities associated with obesity as well as diseases resulting from it due to its distinct mechanism of action. The Phase III trial of this pipeline drug for treating type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity started on August 28, 2023. The results of a Phase II clinical trial have demonstrated significant weight reduction in overweight and obese adults. Specifically, the trial reported an average weight loss of 17.5% and 24.4% at 24 and 48 weeks, respectively. CONCLUSIONS: These findings hold promise for the development of effective weight loss interventions in this population group. There is a need for more phase III studies to provide sufficient clinical evidence for the effectiveness of retatrutide, as current evidence is limited to phase II studies and has yet to prove its worth in a larger population. Here, we aimed to provide an overview of retatrutide's safety and effectiveness in treating obesity.

Deucravacitinib: moderate-to-severe plaque psoriasis preventable?

Psoriasis is a persistent, inflammatory, and autoimmune condition that is difficult to treat. Estimates of the prevalence of psoriasis in people range from 0.27 % (95 % confidence interval 0.17 to 0.36) to 11.4 %, depending on factors such as age, sex, geography, ethnicity, genetics, and environmental factors. While systemic treatments are typically required for patients with moderate-to-severe instances of psoriasis, topical therapies are frequently effective for treating minor forms. In fact, phototherapy is frequently constrained by logistical considerations, and conventional systemic therapies are frequently avoided due to contraindications or the danger of adverse outcomes. In order to better serve the patient and achieve a greater level of quality of life, especially in order to sustain long-term efficacy, there is still a need for innovative therapies, which are always welcomed. Deucravacitinib is a first-in-class oral tyrosine kinase 2 (TYK2) inhibitor that is extremely selective. Through an allosteric mechanism, it stabilises an inhibitory connection between the regulatory and catalytic domains of TYK2's pseudokinase regulatory domain, which is catalytically inactive. This can be used to treat a variety of immune-mediated conditions, such as inflammatory bowel disease, lupus, psoriatic arthritis, and psoriasis. US-FDA has approved this drug on 9 September 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article aims to review the current knowledge on the efficacy and safety of deucravacitinib for the management of psoriasis.

Pozelimab, a human monoclonal immunoglobulin for the treatment of CHAPLE disease.

The complement is a crucial factor of the innate immune system. However, its activation can lead to various diseases, so it needs to be controlled. In mammals, surface-bound complement regulatory proteins safeguard cells from uncontrolled complement-mediated lysis. One of the human complement regulators is CD55, also known as the decay-accelerating factor (DAF), a single-chain, type I cell surface protein anchored to glycosylphosphatidylinositol (GPI). The genetic loss of the complement regulatory protein CD55 leads to a fatal illness known as CHAPLE disease. The complement and innate immunity become hyperactive in this disease, causing angiopathic thrombosis and protein-losing enteropathy. Patients with CHAPLE disease experience abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and swelling. This genetic condition has no known cure, and managing its symptoms can be challenging. Pozelimab, a human monoclonal immunoglobulin IgG4 antibody, is a drug that targets the terminal complement protein C5. The drug has a high affinity for both wild-type and variant human C5. Pozelimab has received designations such as fast track, orphan drug, and rare pediatric disease, making it a significant medical breakthrough. It is currently the only available treatment for this disease. In this review, we have summarized the preclinical and clinical data on pozelimab.

Treatment Cost Along With Pattern of Disease and Therapy in the Intensive Care Unit of a Tertiary Care Teaching Hospital in India.

Background The intensive care unit (ICU) represents an important platform for conducting drug utilization analysis using defined daily dose (DDD)/100 bed-days and the financial burden of treatment as patients are seriously ill and are often suffering from chronic critical illnesses. Therefore, in this study, we evaluated the drug utilization patterns and cost of treatment in the ICU. Methods A retrospective observational analysis of the medical records obtained for the medical ICU of an apex tertiary care teaching hospital in central India was conducted for a period of three years from 2017 to 2019. All the patients admitted to the medical ICU during the study tenure were included in the study. Patients hospitalized in neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), and surgical ICU were excluded from the study. The socio-demographic and clinical data, utilization of different classes of drugs, WHO-Anatomic Therapeutic Chemical (WHO-ATC) classification, DDD/100 bed days, hospital stay, etc. were analyzed. A partial pharmaco-economic analysis of the average cost of admission to patients was done. Results Data from 280 patients was assessed. The mean age was 47 ± 19.18 years and 58% were males. Antibiotics and injections were prescribed to 96% and 97.5% of the patients, respectively, during their ICU stay (median: seven days). Antimicrobial drugs were most frequently prescribed (n=1096, 68%); the most common were beta-lactams and carbapenems, followed by drugs acting on the central nervous system (5%) and cardiovascular system (4.3%). Cefoperazone/sulbactum, ceftriaxone, and piperacillin/tazobactam were the most utilized antibiotics with 8, 16, and 6 DDD/100 bed-days, respectively, while proton pump inhibitors, analgesics, and anti-epileptics were the most frequently prescribed non-antimicrobial drug class. The median cost of treatment per ICU admission was Indian Rupees (INR) 23,347 (IQR 12,552- 65,524). Conclusion Drug utilization assessment provides crucial information for understanding the usage of drugs in the settings of the ICU, and should be conducted regularly to help in the proper planning and implementation of rational drug use. Treatment costs reflect the high economic burden seen in ICU admissions.

Adverse events following Covaxin administration among adolescents (15-18 years) - A pharmacovigilance study in a district in Northern India.

Introduction: The study was undertaken to observe the adverse event following immunization (AEFI) to the Covaxin vaccine in young adolescents in the age group of 15-18 years in a district in Northern India. The study was conducted to assess the safety profile of the COVAXIN vaccine. Methodology: This was a prospective observational study conducted at rural and urban health centers of a district in Northern India. We included the beneficiaries of the COVAXIN between the age of 15 and 18 years. The administration of the COVAXIN occurred in our district from January 2022. Periodic visits were conducted to the urban and rural health centers of the city to record any suspected adverse drug reaction following immunization in the defined population. The study was conducted for a period of 1 year (January 2022 to December 2022). Results: A total of 72,771 adolescents (15-18 years) received the first dose of Covaxin and 49,046 received the second dose. No adverse drug event following immunization was reported during the study. Conclusion: Thus, it can be concluded that Covaxin was found to be safe in adolescents (15-18 years).

Safety monitoring of precautionary third dose of COVID-19 vaccines in a district in Northern India.

Background: The World Health Organization (WHO) declared Coronavirus disease-19 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) a pandemic on March 11, 2020. On 16th January 2021, India began its vaccination programme using two COVID-19 vaccines (Covishield and Covaxin). Precautionary dose (booster shots) was administered to health and front-line workers in the beginning and then to all eligible populations. Material and Methods: This was a descriptive observational study conducted in the COVID-19 vaccination centres of Karnal district and the ADR monitoring centre, KCGMC, Karnal. During the visits to vaccination centres, all beneficiaries of the precautionary third dose of COVID-19 vaccines as well as healthcare workers were sensitized to report in case of any adverse event following vaccination as part of the policy of the vaccination programme run by the government and Pharmacovigilance Programme of India. The data were collected in suspected adverse drug reaction (ADR) reporting form version 1.4, and causality assessment was done as per the WHO-UMC scale. The data were analysed as simple proportions and percentages. Results: The booster dose was administered to 72,853 individuals, while the 1st dose and 2nd dose were given to 13,30,042 and 10,73,050, respectively. Only three ADRs were reported with the booster dose in 34 vaccination centres in the Karnal district. These three ADRs were classified as unlikely on causality assessment and hence not included in the analysis. Conclusion: The booster dose administered for the prevention of COVID-19 has been found to be reasonably safe. The population who received COVID-19 booster doses was significantly less than the populations who received the first and second doses, which suggests a low acceptance rate.