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Purpose: The involvement of the orexin system in the physiopathology of insomnia has been rapidly increasing in understanding. In this sense, daridorexant was the third orexin receptor antagonist approved by the FDA in January 2022. This review aims to summarize the chemistry, pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability profile of daridorexant for the treatment of insomnia disorder. Methods: We performed a review of daridorexant for the treatment of insomnia disorder. The search was carried out in Medline via PubMed, Embase, and clinical trials, up to March 2022. Results: Daridorexant 25 and 50 mg had more significant improvement for the wake after sleep onset (WASO), latency to persistent sleep (LPS), and subjective total sleep time (sTST) than placebo. In addition, daridorexant 50 mg was better for Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) than placebo. The most common adverse events were nasopharyngitis and headache. Conclusion: Daridorexant was efficacious and safe. Studies that evaluate the long-term safety and compare daridorexant with benzodiazepines, benzodiazepine receptor agonists, sedative antidepressants, and other orexin receptor antagonists are required. [ABSTRACT FROM AUTHOR]

Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day. Efgartigimod is a human IgG1–derived Fc fragment modified at five residues to increase its affinity for the neonatal Fc receptor by Abdeg technology. Thus, efgartigimod binds to the neonatal Fc receptor and decreases the levels of IgG, including autoantibodies of this isotype. For acetylcholine receptor (AChR) antibody-positive patients, efgartigimod had a higher proportion of MG-ADL responders than placebo in the first treatment cycle. The mean changes of multiple outcomes from baseline were better for efgartigimod than placebo from weeks 1 to 7 in the first treatment cycle. The decrease of IgG and AChR autoantibodies was 61.3% and 57.6% one week after the first treatment cycle ends, respectively. The most common adverse events were headache, nasopharyngitis, nausea, and diarrhea, which occurred in the same proportion in the efgartigimod and placebo groups. Urinary and upper respiratory tract infections were twice as frequent in efgartigimod-treated patients. Efgartigimod was efficacious and safe for generalized myasthenia patients with AChR antibody-positive patients. These findings need to be confirmed in AChR antibody-negative patients, and long-term safety studies are currently ongoing. Myasthenia gravis patients have a high level of autoantibodies, which can cause fluctuating muscle weakness. In this regard, efgartigimod is a new drug approved to treat myasthenia gravis that decreases antibody levels and symptom improvement. Furthermore, this drug was safe for these patients. [ABSTRACT FROM AUTHOR]

Background: Conventional synthetic disease-modifying antirheumatic drugs are the first-line treatment to inhibit the progression of psoriatic arthritis. Despite their widespread clinical use, few studies have been conducted to compare these drugs for psoriatic arthritis. Methods: a longitudinal study was carried out based on a centered patient national database in Brazil. Market share of drugs, medication persistence, drug costs, and cost per response were evaluated. Results: a total of 1,999 individuals with psoriatic arthritis were included. Methotrexate was the most used drug (44.4%), followed by leflunomide (40.6%), ciclosporin (8.2%), and sulfasalazine (6.8%). Methotrexate and leflunomide had a greater market share than ciclosporin and sulfasalazine over years. Medication persistence was higher for leflunomide (58.9 and 28.2%), followed by methotrexate (51.6 and 25.4%) at six and 12 months, respectively. Leflunomide was deemed the most expensive drug, with an average annual cost of $317.25, followed by sulfasalazine ($106.47), ciclosporin ($97.64), and methotrexate ($40.23). Methotrexate was the drug being the lowest cost per response. Conclusion: Methotrexate had the best cost per response ratio, owing to its lower cost and a slightly lower proportion of persistent patients when compared to leflunomide. Leflunomide had a slightly higher medication persistence than methotrexate, but it was the most expensive drug. [ABSTRACT FROM AUTHOR]

Background: TNF inhibitors are costly drugs supplied generally on health systems or private insurances. Performance analysis is essential to verify the results achieved by health technologies in these systems. The objective of the study was to compare the two most used biological drugs for the treatment of psoriatic arthritis (PsA) in Brazil. Methods: A cost-utility analysis was built using a Markov model, with a five-year time horizon, a discount rate of 5%, and from the perspective of the Unified Health System. Deterministic and probabilistic sensitivity analyses were performed. Results: Etanercept was the most cost-effective drug. Adalimumab became the most cost-effective drug in one of the four analysis scenarios with a willingness to pay from one gross domestic product per capita. The deterministic sensitivity analysis identified that the cost parameters had the greatest impact on the most effective drug. The probabilistic sensitivity analysis indicated that etanercept is the drug most likely to be cost-effective. Conclusion: The difference between the drugs in terms of utility was minimal and the costs were the main factor that impacted the cost-utility ratio, which points to the benefits of price renegotiation for the efficient allocation of resources in the health system. [ABSTRACT FROM AUTHOR]

Background: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil.Methods: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty.Results: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses.Conclusion: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate and compare the use of subcutaneous anti-TNF for RA in a Brazilian real-life setting. Methods: A prospective cohort of biological disease-modifying antirheumatic drug (bDMARD)-naïve patients treated with adalimumab, etanercept, golimumab, and certolizumab was developed. Medication persistence, disease activity by the Clinical Disease Activity Index (CDAI), functionality by the Health Assessment Questionnaire (HAQ), quality of life by the European Quality of Life 5 Dimensions (EQ-5D), and safety were evaluated at 6 and 12 months. Results: In a total of 327 individuals, 211 (64.5%) were persistent at 12 months. Patients improved after the use of anti-TNF, with a reduction in the mean of CDAI and HAQ, in addition to an increase in the mean of EQ-5D (p < 0.05). The number of patients who achieved the clinical response was 114 (34.86%) by CDAI, 212 (64.83%) by HAQ, and 215 (65.75%) by EQ-5D at 12 months. There were no statistically significant differences among the drugs (p > 0.05). The anti-TNF was well tolerated. Conclusion: Anti-TNF reduced disease activity, in addition to improving patients' functionality and quality of life. Additional pharmacotherapeutic monitoring can be essential to achieve better results. [ABSTRACT FROM AUTHOR]

Background: Biological therapies have a significant economic and clinical burden but, in general, lose their effectiveness over time. This study evaluated the medication persistence and costs associated to use of anti-TNF agents for psoriatic arthritis (PsA) treatment. Methods: A historical cohort composed of individuals in Brazil with PsA diagnosis was developed during the period between 2010 and 2015. The difference among the anti-TNF agents was verified by the log-rank test. The predictors of medication non-persistence were identified by Cox regression. The costs were compared by variance analysis with Bonferroni correction. Results: 11,008 patients were analyzed. Adalimumab (51%) was the most used anti-TNF agent. Individuals using adalimumab presented higher medication persistence as compared to etanercept and infliximab. The costs with anti-TNF agents corresponded to 90% of the total costs and were similar among anti-TNF agents. The non-persistence predictors were female sex, younger patients, to live in the Northeastern and Northern regions of Brazil, to use infliximab and etanercept, and have more comorbidities. Conclusion: The direct costs with anti-TNF agents were the main component of total costs. Outpatient and inpatient costs increase when medication persistence decreases. A considerable price reduction of anti-TNF agents has been observed over the years. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the persistence of biological drugs used as the first line of biological treatment in patients diagnosed with rheumatoid arthritis. The predictors associated with persistence have also been verified. Methods: We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months. Results: A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions. Conclusion: The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the use of drugs and the factors associated with polypharmacy in patients with diabetes mellitus (DM) in Minas Gerais. Descriptive analysis of drugs in use and logistic regression to estimate the association between socio-demographic and clinical characteristics with polypharmacy were performed. Of the 2619 respondents, 56.5% were in polypharmacy. Drugs for DM, agent in renin-angiotensin system, and diuretics are the most frequently used. Factors such as age, comorbidities and increased access to health services were associated with polypharmacy. It was observed high prevalence of polypharmacy, which requires a suitable care and better quality of drug use in this population. [ABSTRACT FROM AUTHOR]