Daridorexant for the treatment of insomnia disorder: findings and implications.

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.

Use of medicinal plants during COVID-19 pandemic in Brazil.

Medicinal plants are an integrative and complementary health practice widely used by the population. However, its use is not without risks. This study assessed the profile and associated factors with the traditional use of medicinal plants. To this end, a cross-sectional survey study was conducted in a southeastern Brazilian city. Descriptive analysis was performed by frequency distribution and median and interquartile range. Associated factors with the use of medicinal plants were analyzed using Poisson regression with robust variance. A total of 641 people were interviewed, of whom 258 (40.2%) reported using medicinal plants. A total of 79 distinct plants were identified, of whom Melissa officinalis (31.0%), Peumus boldus (24.4%), Mentha spicata (20.9%), Matricaria recutita L. (18.2%), Rosmarinus officinalis (17.0%), and Foeniculum vulgare (14.7%) were the most used. There were no reports of medicinal plants used to treat COVID-19. However, anxiety was the most frequently cited indication for using medicinal plants, a health condition exacerbated by the COVID-19 pandemic. Furthermore, the use of medicinal plants for treating respiratory and gastrointestinal symptoms similar to those in COVID-19 has been identified. There was an association between the use of medicinal plants and females, non-white, lower schooling, higher income, and comorbidities.

Self-Medication during the COVID-19 Pandemic in Brazil: Findings and Implications to Promote the Rational Use of Medicines.

Self-medication is identified by the consumption of medications without a prescription or guidance from a qualified prescribing professional. This study estimated the prevalence, profile, and associated factors with self-medication during the COVID-19 pandemic in Brazil. A cross-sectional study was conducted through a household survey in the Alegre city, from November to December 2021. Descriptive analysis was performed for the sociodemographic and clinical characteristics of the interviewees. Poisson regression with robust variance was used to identify the association of sociodemographic and clinical variables with self-medication. A total of 654 people were interviewed, of whom 69.4% were self-medicating. The younger age group (PR = 1.13; 95% CI = 1.01-1.26), female gender (PR = 1.19; 95% CI = 1.04-1.37), consumption of alcoholic beverages (PR = 1.13; 95% CI = 1.01-1.25), and problems with adherence to pharmacological treatment (PR = 1.15; 95% CI = 1.04-1.28) were associated with self-medication, while the occurrence of polypharmacy (PR = 0.80; 95% CI = 0.68-0.95) was a protective factor for self-medication. Self-medication was directly related to over-the-counter drugs, with analgesics dipyrone and paracetamol being the most commonly used. Self-medication consumption of prescription drugs, including those under special control, was identified to a lesser extent.

Small molecule CGRP receptor antagonists for the preventive treatment of migraine: A review.

OBJECTIVE: To review the chemistry, pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability profile of small molecule CGRP receptor antagonists for the preventive treatment of migraine. MATERIAL AND METHODS: We conducted a review of atogepant, rimegepant, and zavegepant for the preventive treatment of migraine. The search was carried out in Medline via PubMed, Embase, and Clinical trials, up to January 2022. RESULTS: Five hundred ninety-nine studies were found, of which 113 were in Medline via PubMed and 486 in Embase. The review included ten studies. Moreover, 16 clinical trials evaluated atogepant, rimegepant, and zavegepant. Atogepant and rimegepant reduced the number of migraine days per month and improved the Migraine-Specific Quality of Life Questionnaire role function (restrictive domain score). The frequency of adverse events and the treatment discontinuation were similar between the small molecule CGRP receptor antagonists and placebo. Zavegepant is currently being evaluated in a phase-2/3 clinical trial for migraine prevention, with no available findings. CONCLUSION: Atogepant and rimegepant were effective and safe for the preventive treatment of migraine in adults. Long-term safety studies and comparisons of atogepant and rimegepant with other established treatments for migraine prevention are required.

TransCon human growth hormone for children with growth hormone deficiency: a technology evaluation.

INTRODUCTION: Standard-of-care treatment for growth hormone deficiency consists of daily subcutaneous injections of recombinant human growth hormone, also known as somatropin. Although somatropin treatment is well established, the burden of daily injections can lead to poor adherence and quality of life. In this regard, a TransCon human growth hormone (lonapegsomatropin-tcgd) technology was developed to optimize the therapeutic effect of daily somatropin for the treatment of children with growth hormone deficiency. AREAS COVERED: The authors reviewed the effects of lonapegsomatropin-tcgd in children with growth hormone deficiency. EXPERT OPINION: Lonapegsomatropin-tcgd was found to be non-inferior to and superior to daily somatropin for annualized height velocity. In addition, the safety was comparable between them. As a result, the convenient dosing of lonapegsomatropin-tcgd has the potential to improve patient adherence, leading to increased efficacy and quality of life. Medication adherence, quality of life, long-term safety, and cost-effectiveness studies comparing lonapegsomatropin-tcgd and daily somatropin are required to confirm these possible benefits.

Abdeg technology for the treatment of myasthenia gravis: efgartigimod drug experience.

INTRODUCTION: Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day. AREAS COVERED: 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. EXPERT OPINION: 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.[Figure: see text].

Economic evaluation of adalimumab versus etanercept for psoriatic arthritis in a Brazilian real-world model.

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.

Conventional Synthetic Disease-Modifying Anti-rheumatic Drugs for Psoriatic Arthritis: Findings and Implications From a Patient Centered Longitudinal Study in Brazil.

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.

Cost-utility analysis of the anti-TNF therapy for rheumatoid arthritis in a real-world based model.

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.

Comparative persistence of anti-tumor necrosis factor therapy in ankylosing spondylitis patients: a multicenter international study.

Objective: To evaluate persistence on conventional DMARDs (cDMARDs) and anti-TNF therapies, and to identify potential determinants of discontinuation among individuals with ankylosing spondylitis (AS) living in Brazil and Quebec, Canada.Methods: We conducted a cohort study of AS patients using health administrative data (2010-2015). One-year and 2-year persistence rates were assessed. Cox regression was used to identify potential determinants of therapy discontinuation.Results: One-year persistence was less likely in Brazil for both anti-TNF and cDMARDs (Brazil: 62.1 and 30.7%, Quebec: 66.9 and 67.0%). The 2-year persistence rates were lower for both anti-TNF and cDMARD, but remained higher in Quebec (Brazil: 47.9 and 18.1%, Quebec: 51.5 and 53.5%). In multivariate Cox regression analysis, age, sex and comorbidities were associated with persistence in both countries. In Quebec, persistence did not differ between rural and urban regions or with socioeconomic status. While in Brazil, patients in regions with higher Human Development Index and those in cities with lower Gini index were less likely to discontinue therapy.Conclusions: Canadian AS patients were more likely to persist on therapy compared to Brazilian patients, although rates were lower at 2 years in both countries. Socioeconomic disparity in persistence was found in Brazil, but not in Quebec.

FIRST LINE OF SUBCUTANEOUS ANTI-TNF THERAPY FOR RHEUMATOID ARTHRITIS: A PROSPECTIVE COHORT STUDY.

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.

Impact of biologic DMARDs on quality of life: 12-month results of a rheumatic diseases cohort using the Brazilian EQ-5D tariff.

OBJECTIVES: To evaluate the association between biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) use and quality of life (QoL) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). PATIENTS AND METHODS: We evaluated adult patients prescribed biological DMARDs whose quality of life was evaluated at six and 12 months. The EuroQol 5 dimensions (EQ-5D) was used with the Brazilian tariff. RESULTS: Patients receiving bDMARDs had significant improvements in quality of life after 6 and 12 months (p < 0.001), regardless of the rheumatic condition and the therapeutic regimen (bDMARDs vs bDMARDs plus synthetic DMARDs) (ANCOVA; p > 0.05). At the end of one year, 62.6% of the participants presented significant clinical improvement in QoL. According to a sensitivity analysis, QoL results in the complete case analysis and in the multiple imputation model yielded similar conclusions. Patients with two or more comorbidities and worse QoL and disability status on baseline presented worse QoL at 12 months when compared to those with better disability status on baseline. Baseline clinical disease measured by activity indexes (BASDAI and CDAI) did not influence QoL after 12 months of bDMARD treatment. Pain and malaise were the EQ-5D domain that most influenced quality of life. CONCLUSION: Patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis displayed significantly better QoL levels following treatment with DMARDs.

Biological therapy in the treatment of psoriatic arthritis: economic and epidemiological considerations.

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.

Access to high-cost medications for psoriatic arthritis in the National Health System in Brazil: the long path up to dispensation.

BACKGROUND: Pharmaceutical Assistance (PA) is a dynamic and multidisciplinary process that aims to supply health systems, programs or services with quality medicines, enabling access and health care, in an efficient and timely manner. The objective of the study was to evaluate the profile of administrative processes for the treatment of PsA, identify the time elapsed in the flow of processes and its associated factors. METHODS: A cross-sectional study of medication requests for the treatment of PsA was carried out between November 2014 and December 2016. Linear regression was used to verify the factors associated with time to delivery. RESULTS: A total of 218 cases containing 250 drugs were analyzed. The median time between the medical appointment and the first dispensation was 66 days (interquartile range, 44-90). The State proceedings, which includes requesting the drug until the authorization of treatment, was the stage that most contributed to the total time spent. The factors associated with the longer time to delivery of medications were prescriptions coming from clinics and specialty centers, from dermatologists, non-authorized processes and non-persistent patients in the treatment in 12 months. CONCLUSION: The median time to receive medicines for the PsA treatment in Belo Horizonte health region after a medical prescription was higher than 2 months. The time between the solicitation of the medicines and the authorization of the treatment in the SUS (State administrative procedure) was the main component of the total time spent.

First line of biological drugs in rheumatoid arthritis: a medication persistence analysis.

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.

Effectiveness and safety of anti-TNF in psoriatic arthritis patients in Brazil: a post-incorporation analysis.

AIM: Psoriatic arthritis is a chronic disease that can result in disability and decreased quality of life. MATERIALS & METHODS: A prospective cohort was conducted in Brazil. Disease activity was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI), functionality by the Health Assessment Questionnaire Disability Index (HAQ-DI) and the quality of life by the EuroQol 5D (EQ-5D). RESULTS: In total, 122 patients were included. After 6 months, a median reduction of 2.03 in the BASDAI, 7.80 in the CDAI, 0.63 in the HAQ-DI and increase of 0.12 in the EQ-5D was observed. A good clinical response was observed in 45.5% of the patients by BASDAI and 54.5% by CDAI. Higher education and better quality of life were identified as predictors of effectiveness. The most common side effects were the infections. CONCLUSION: Anti-TNF-α drugs were effective and safe. The incorporation of them into the Brazilian Public Health System has provided therapeutic alternatives to the treatment of psoriatic arthritis.

Quality of life of patients with Diabetes Mellitus Types 1 and 2 from a referal health centre in Minas Gerais, Brazil.

UNLABELLED: Quality of life (QoL) characteristics are important in patients with diabetes mellitus (DM 1 and 2). AIM: Evaluate QoL and DM-associated factors among diabetic patients. METHODS: Patients attending a University Hospital were interviewed about their sociodemographic, clinical and QoL characteristics, with QoL measured via the EQ-5D. Descriptive analysis, correlation, linear regression, univariate and multivariate analysis were performed. RESULTS: 346 patients took part, comprising 67% women, 59% with DM2, and 32% DM1. DM 1 patients had a mean QoL score of 0.7369, with retinopathy, depression, dyslipidemia and a serious hypoglycemic crisis significantly reducing QoL. Patients with DM type 2 had a mean QoL score of 0.6582, with hypertension, neuropathy, depression, cancer and dyslipidemia significantly reducing QoL. Reduced QoL also correlated with a lack of physical exercise. Males with both DM1 and 2 had a better QoL than females. CONCLUSION: Need for better disease monitoring and control combined with effective activities to improve self-care, reduce complications and improve patients' QoL.