Off-label Medications Research Articles

Spesolimab decreases generalized pustular psoriasis (GPP) body surface area (BSA) over time in patients switching from conventional systemic treatments: Results from the EFFISAYIL® 2 trial

Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease. Most patients experience chronic skin symptoms between flares which can lead to significant patient burden. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved in the United States to treat GPP in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. EFFISAYIL® 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous (SC) spesolimab in GPP. Here, we report the effects on GPP body surface area (BSA) over time in patients switched from a small-molecule systemic therapy at randomization when treated with the FDA approved spesolimab dosing regimen (600 mg loading dose, then 300 mg maintenance dose every 4 weeks) in EFFISAYIL® 2. Total BSA was determined based on a weighted average of the extent of involvement over 4 main body regions, with head = 10%, upper extremities = 20%, trunk = 30%, and lower extremities = 40%. Total BSA involvement was calculated for each subject at 4 timepoints (baseline, Week 4, Week 16, and Week 48). Data collected closest to the given time points were used by including the effect of potential intravenous spesolimab treatment and subsequent open-label SC spesolimab treatment in patients who experienced a flare. The data were analyzed as observed. Within the FDA approved spesolimab regimen group, the average BSA for patients who stopped a systemic medication for GPP (Total N=22; acitretin = 13, cyclosporine = 7, methotrexate = 1, acitretin/methotrexate = 1) was 11.1 at baseline, decreasing to 8.2 at Week 4, 6.4 at Week 16, and then ending at 3.6 at Week 48. Total BSA involvement decreased over the 48 weeks of the trial in spesolimab-treated patients who stopped an off-label systemic medication for GPP at randomization.

Association of Psychotropic Prescriptions With Non-Registered Indications and the Risk of Mortality in Older Adults: A Danish Nationwide Cohort Study.

Psychotropic drug use is common in older adults, with off-label use reported despite limited understanding of the safety outcomes compared to on-label use. Incomplete recordings of treatment indications in the Danish National Prescription Register (DNPR) raise concerns about potential off-label medication use, particularly among older adults. We, therefore, investigated the association between psychotropic prescriptions with non-registered indications in DNPR and the 1-year all-cause mortality in older adults, including subgroups with any psychiatric disorders, depression, or dementia. Register-based cohort study following all older adults (≥ 65) who redeemed a first-time (since 1995) prescription of either antidepressants, antipsychotics, or benzodiazepine during 2006-2017. Redemption of a prescription with non-registered indications in the DNPR was the exposure. The outcome, 1-year all-cause mortality was analyzed using Poisson regression, estimating incidence rate ratios with 95% confidence intervals, adjusting for socio-demographics and clinical factors. 32% of prescriptions filled by 202,067 individuals for antidepressants, 37% of 97,387 for antipsychotics, and 22% of 130,471 for benzodiazepines had non-registered indications. No significant differences in mortality rates were found for antidepressants and antipsychotics with non-registered indications, while higher mortality rates were associated with benzodiazepines, mitigated when excluding individuals receiving intravenous administrations representing end-of-life treatment. The results remained consistent in subgroup analyses in patients with any psychiatric disorders, depression, or dementia and further stratified analyses by sex and age. We found that while psychotropic prescriptions with non-registered indications in DNPR were prevalent in older adults, they were not associated with excess mortality.

Treatment patterns and characteristics of patients with Post-Traumatic Stress Disorder (PTSD): A retrospective claims analysis among commercially insured population.

This retrospective claims analysis explored the treatment utilization and characteristics among patients with post-traumatic stress disorder (PTSD) of different severity. The index date was the first PTSD claim. The analysis observed 12 months pre- and 24 months post-index. Adults with insurance gaps, cancer, or acute PTSD during the observation were excluded. Patients were categorized into three severity cohorts based on treatment and healthcare services utilization for PTSD: 1. Baseline PTSD (BP) (no PTSD visits post-index, no FDA-approved medications/ psychotherapy, and no severe mental health comorbidities); 2. PTSD without Comorbidities (PwoC) (≥1 PTSD visits post-index and no severe mental health conditions); 3. PTSD with Comorbidities (PwC) (≥1 PTSD visits post-index and severe mental health comorbidities present). For the primary analysis, cohorts were propensity-score matched. A sub-analysis examined patients with PTSD and Substance or Alcohol Use Disorder (SUD/AUD). The primary analysis observed 1714 BP, 1681 PwoC, and 1681 PwC patients. Treatment utilization rates were highest among PwC vs. other cohorts (84.5% psychotherapy, 76.1% off-label medications, and 26.1% FDA-approved medications [p<0.001]). PwC cohort also had the highest number of psychotherapy sessions and medication prescriptions per patient (20.1 sessions, 12.6 off-label prescriptions, and 2.0 FDA-approved prescriptions [p<0.001]). The proportion of days covered (PDC) indicated low medication adherence (0.25-0.40) with adherent patient rates (PDC ≥0.80) between 8.0-17.5%. The SUD/AUD sub-analysis identified 85 BP, 537 PwoC, and 3154 PwC patients. Conclusions were similar, with PwC cohort having highest treatment utilization rates (87.1% psychotherapy, 85.0% off-label medications, 28.2% FDA-approved medications [p≤0.013] with 24.4 sessions, 16.1 off-label prescriptions, and 2.0 FDA-approved prescriptions per patient [p≤0.002]). Only 4.7-11.4% of patients were adherent. PwC patients received psychotherapy and pharmacotherapy more frequently than PwoC and BP patients. Medication adherence among treated patients was low. Patients with SUD/AUD had numerically higher treatment utilization and lower medication adherence.

Schizophrenia, Off-Label Antipsychotics, and Dementia Risk in People with HIV.

Comorbidities such as schizophrenia and medication such as antipsychotics may influence the risk of dementia among people living with HIV (PLWH). The objective of this paper is to assess the associations among HIV patients with schizophrenia, off-label antipsychotics, and dementia risk. US Department of Veterans Affairs healthcare facilities from 2000 to September 2023. Retrospective cohort study of PLWH treated by the U.S. Department of Veterans Affairs with prior history of schizophrenia, off-label antipsychotic use and neither schizophrenia nor antipsychotic use. Propensity score matched non-HIV controls were included for the respective HIV groups. The hazard of dementia is estimated using Cox proportional hazards models. PLWH and schizophrenia, were found to have a 2.49 higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=2.49, 95%CI=(1.85-3.35)). PLWH and off-label antipsychotic use were found to have a 1.77-fold higher hazard of dementia compared to HIV patients with no history of schizophrenia or antipsychotic medication use (HR=1.77, 95% CI=(1.37-2.28)). Propensity score matched analysis reveals that, among schizophrenia patientis, those with HIV had a 1.65-fold higher hazard of dementia (HR=1.65, 95%CI=(1.12-2.44)). Among patients with no schizophrenia or antipsychotic medication, those with HIV had a 1.47 fold higher hazard of dementia (HR=1.47, 95%CI=(1.33-1.63)). This study demonstrates that among PLWH, history of schizophrenia or off-label antipsychotic medication use are associated with substantial increases in dementia incidence. Furthermore, propensity-matched control analysis reveals that HIV infection itself is independently and significantly associated with elevated dementia risk.

Unveiling Disparities: Exploring Overmedication of Black Foster Care Youth and How Implicit Bias Contributes

Background:Black youth are overrepresented in the foster care system, and research is needed to reveal the impact of their overmedication (Cénat et al., 2021; Dettlaff &amp; Boyd, 2020; Godoy et al., 2022; Lee et al., 2015; Montgomery, 2022; Williams-But‐ ler, 2023).Objective:This article examines misdiagnoses, overprescribed psychotropics, and off-label medication use to address behavioral concerns (American Civil Liberties Union Maryland v. Maryland, 2023; Cullins &amp; Moore, 2020; Fadus et al., 2020; Mizock &amp; Harkins, 2011) and investigates the contribution of implicit bias to find equitable and nondiscriminatory solutions.Methods:A systematic literature review was conducted to identify themes surrounding racial disparities within the child welfare system. Articles that were published within the last five years were prioritized except for those with unique findings or a specific lens of inquiry. Foundational references such as relevant legislation were also used to support the research questions.Findings:The literature reveals significant and clear disparities in the treatment of Black youth within the child welfare system. Black foster care youth are often medicated at disproportionately high rates.Conclusions:The findings suggest that more culturally intelligent interventions are necessary to ensure Black foster care youth receive adequate and appropriate assessment and treatment.

Off-Label Pediatric Medication Prescribing and Dispensing: Awareness and Attitudes among Community Pharmacists: A Questionnaire-Based Study.

Off-label practice in pediatrics requires relentless engagement from all the health professionals involved. Community pharmacists are the last ones in the prescribing-dispensing chain; therefore, they have the key responsibility of verifying the correctness of a treatment. A cross-sectional study was conducted for assessing the awareness and views of Romanian community pharmacists, regarding off-label drugs in the pediatric population, through a 28-item questionnaire comprising five sections of different topics (general knowledge, frequency of prescribing and dispensing off-label medication, views, and attitudes). The sample size was 236 questionnaires with a response rate of 41.11%. A statistical analysis of the obtained data was performed with GraphPad Prism v.9. The results indicate that 55.1% of the community pharmacists have a good general knowledge and awareness regarding the off-label practice, although the legal frame is unclear. The responses highlight a high frequency of prescribing and request of medication for respiratory conditions (45.3%) and antibiotics (23.5%), with a concerning gap regarding the adverse events related to the off-label treatments (56.7%). A very small percentage of pharmacists (7.1%) contact a fellow healthcare professional when encountering an off-label prescription. In conclusion, in addition to the pharmacist's conduct towards the best interest of the patient, there is a clear need to improve the doctor-pharmacist collaboration in order to make an off-label treatment successful.

N-of-1 trials in epilepsy: A systematic review and lessons paving the way forward.

Defined as prospective single-patient crossover studies with repeated paired cycles of active and control intervention, N-of-1 trials have gained attention as an option to obtain high-quality evidence of efficacy, particularly for patients with rare epilepsies in whom conduction of well-powered randomized controlled trials can be challenging. The objective of this systematic review is to provide an appraisal of the literature on N-of-1 trials in individuals with epilepsy. We searched PubMed and Embase on January 12, 2024, for studies meeting the following criteria: prospectively planned, within-patient, multiple-crossover design in individuals with epilepsy and outcomes related to comorbidities. Information on design, outcome measurements, intervention, and analyses was retrieved. Risk of bias assessment was performed using the Risk of Bias in N-of-1 Trials (RoBiNT) scale. We highlighted methodological aspects of the N-of-1 trials identified and discuss future recommendations. Five studies met our inclusion criteria. An additional multiple-crossover trial that evaluated treatment effects exclusively at group level was also included because of its relevance to N-of-1 study methodology. The studies enrolled individuals with focal seizures, absences or cognitive impairement and electrographic discharges. Treatments included established or investigational antiseizure medications, off-label medications, neurostimulation or lifestyle intervention. Three of the five N-of-1 trials reported on individual cases. The studies' strengths were the use of individualized treatment dosages and symptom-specific patient-reported outcomes. Limitations were related to minimal reporting of baseline characteristics and seizure burden. The trials identified by our search exemplify how the N-of-1 design can be applied to assess interventions in individuals with epilepsy-related disorders. Future N-of-1 trials of antiseizure interventions should take into account baseline seizure frequency, should apply statistical models suited to capture seizure frequency changes reliably and make predefined interim assessments. Non-seizure outcome measures evaluable over short periods should be considered. Tailored N-of-1 methodology could pave the way to evidence-based, treatment selection for patients with rare epilepsies.

Real-World Prescription Data for Intrathecal Drug Delivery: A Retrospective Analysis in 32,784 Patients

ObjectivesCurrently, there are three monotherapy drugs approved by the United States Food and Drug Administration (FDA) for use in intrathecal drug delivery systems (IDDS): morphine, ziconotide, and baclofen. In practice, use includes alternate drugs, drug combinations, and drug concentrations. There is a paucity of real-world data examining prescription patterns for IDDS. Our analysis explores a one-year sample of prescription intrathecal (IT) medications from a large pharmaceutical data base to characterize medication usage in IDDS. Materials and MethodsData were provided by an accredited pharmacy as a deidentified data base of IT drug prescriptions. Statistical analyses included rates of monotherapy vs combination therapies, frequencies of various IT prescriptions, use of on- vs off-label medications, and opioid vs nonopioid formulations. ResultsData were extracted from February 1, 2021 to February 14, 2022. No patients were excluded. The initial sample comprised 49,917 individual IT prescriptions for 32,784 patients. Monotherapies constituted 55.0% of all prescriptions (27,475/49,917). Of these, 23,257 prescriptions (84.6%) were opioid based, with the most common medications being morphine (46.5%), hydromorphone (39.4%), and fentanyl (13.5%). Although 29.3% of all prescriptions were for one of the FDA-approved medications, only 7.9% used FDA-approved concentrations; 9865 patients underwent ≥one prescription change in the study period—16.7% of whom were initially prescribed medications that met the approved, on-label indications for the pump before being switched to off-label concentrations or combinations to address clinical needs. ConclusionsDespite the prevalence of IDDS for managing chronic, intractable pain, minimal data exist on real-world prescription practices. Our study found that FDA-approved IT formulations accounted for the minority of prescriptions, indicating significant practice variation, with off-label prescriptions being common.

The legal status of off-label preparations and legal aspects of their application in The Russian Federation

For many years, the medications "outside of instruction" (the so-called "off-label" ones) had no single-valued legal status in the Russian Federation and other countries that entailed number of problems. Most of them had to do with schemes and tactics of treatment of patient, impossibility of proper medical care support, legal responsibility of physician for applying medications outside of attached instruction. The important move in resolving mentioned problem became adoption of the Federal Law "On entering changes in the Federal Law "On Fundamentals of Health Care of Citizen in The Russian Federation" that became first step on the path leading to acquisition by "off-label" its legal status. The analysis of relevant normative legal acts, the Criminal code of the Russian Federation was carried out. The basic conclusions related to application of medications in medical institutions in Russia, to physician strategy in cases requiring application of of medications "outside of instruction" were formulated. In case of applying medications "outside of instruction" without informed voluntary agreement of patient, without utmost necessity, single-handed instead of decision of medical commission or in situations which could be managed without this kind of medications i.e. under unfounded risk the physician can be prosecuted since treatment with off-label medications is considered as insecure according to legislative base currently in force.

Disease-modifying therapies, outcomes, risk factors and severity of COVID-19 in multiple sclerosis: A MENACTRIMS registry based study

BackgroundThere is a lack information regarding risk factors associated with worse COVID-19 outcomes in patients with multiple sclerosis (MS) in the MENA region. MethodsThis is a multicenter, retrospective cohort study that included all MS patients with a suspected or confirmed COVID-19 infection using the MENACTRIMS registry. The association of demographics, disease characteristics, and use of disease-modifying therapies (DMTs) with outcomes and severity of COVID-19 were evaluated by multivariate logistic model. ResultsA total of 600 MS patients with confirmed (n = 542) or highly suspected (n = 58) COVID-19 were analyzed. Seventy-three patients (12.2 %) had a COVID-19 severity score of ≥3 on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death] with a cutoff at 3 [hospitalized and not requiring supplemental oxygen]), and 15 patients (2.5 %) died. Out of 73 patients with a severity score ≥3, 90.4 % were on DMTs; 50.6 % of them were on anti-CD20, including ocrelizumab and rituximab. Multivariate logistic regression showed that older age (odds ratio per 10 years, 1.4 [95 %CI, 1.0–1.8]), disability (OR for EDSS 3.0–5.5, 2.9 [95 %CI. 1.5–5.7], OR for EDSS ≥6.0, 2.3 [95 %CI. 1.0–5.1]), obesity (OR, 3.0 [95 %CI, 1.5–6.0]), and treatment with rituximab (OR, 9.0 [95 %CI, 3.1–25.3]) or off-label immunosuppressive medications (OR, 5.6 [95 %CI. 1.1–27.8]) were risk factors for moderate or severe COVID-19. ConclusionIn this registry-based study of MS patients, age, sex, EDSS, obesity, progressive MS were risk factors for severe COVID-19. Moreover, there was an association found between exposure to anti-CD20 DMTs and COVID-19 severity.

Perceptions and experiences of community pharmacists with off-label prescribing in the pediatric population.

This study aimed to investigate and provide insight into the prevalence and patterns of off-label drug use in the pediatric population from the perspective of community pharmacists, addressing the existing data gap in a developing setting. A questionnaire-based cross-sectional study was conducted on Albanian community pharmacists in June 2021. The online administered survey explored the participants' demographic details, perceptions, and experiences with off-label prescriptions in pediatric patients. The statistical analysis conducted on the survey data comprised the construction of frequency tables and the application of the chi-square test for independence. Three hundred and thirty-six community pharmacists nationwide completed the survey, out of which 186 (55.3%) were practiced in Tirana, the capital of Albania. Over 80% of surveyed pharmacists (n = 275) had encountered off-label drug prescriptions in pediatric patients, yet only 40% of participants reported dispensing medicines for off-label use. Community pharmacists reported that general pediatricians tended to prescribe off-label medications more frequently than pediatric subspecialists or general practitioners. It was found that off-label prescriptions were more frequently observed among children aged between 2 and 11 years. Antibiotics were the most reported medicines for off-label use in this study mentioned in almost all off-label categories. Prescribing medicines for unapproved uses for the treatment of pediatric patients is present in community settings in Albania. This indicates the need for further data collection and analysis to understand off-label practices in our country's pediatric population comprehensively.

Tamsulosin off-label use in kidney stones: Review and survey

This study investigates the effectiveness and healthcare perceptions of Tamsulosin, an off-label medication for kidney stone management. Despite the documented benefits, the quest for alternative treatments like Tamsulosin persists, driven by its advantages and patient satisfaction levels. This research includes a literature review and a survey of pharmacy students’ opinions on Tamsulosin, aiming to bridge the knowledge gap. This study, which involved 38 first-year professional pharmacy students, achieved a 92% response rate. The research used questionnaire that collected demographic information and assessed participants' knowledge and opinions using a Likert scale, which was integrated into a drug informatics course. We analyzed the responses using SPSS software, utilizing descriptive and chi-square statistical methods. The survey, completed by 38 participants, revealed discrepancies between current treatment practices and the students' understandings. Despite Tamsulosin's documented efficacy in facilitating stone passage, significant skepticism exists about its use without FDA approval. The research showed varied levels of understanding and skepticism towards off-label use among the students. Moreover, 70.3% of respondents recognized Tamsulosin's potential for managing kidney stones, despite its lack of FDA approval, indicating a cautious yet acknowledging attitude towards non-approved drug use for organ rejection. There's a noted need for improved education and the dissemination of evidence-based guidelines in clinical practice. The study uncovers varied knowledge and perceptions among healthcare professionals and pharmacy students regarding Tamsulosin's use in kidney stone management. The gap between clinical evidence and survey participants' awareness underscores the importance of further research and education to align clinical practices with evidence-based guidelines

Awareness, Practice, and Views of Pediatricians, General Physicians, and Pharmacists about Prescribing Off-label Medication in Pediatric Patients in Eastern Province, Saudi Arabia.

An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia. A cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05. Among the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%). There are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue.

In vitro and in silico antileishmania activity of voriconazole (Vfend)

American Cutaneous Leishmaniasis (ACL) is a public health problem in 88 countries. The treatment of ATL is based on pentavalent antimony, which has several adverse effects. And through new alternatives for the treatment of leishmaniasis, the use of off-label medications appears. The objective of this work was to evaluate, through in vitro and in silico tests, the activity of voriconazole in tablet form as off-label against the promastigote forms of Leishmania amazonensis and Leishmania guyanensis. In the bioassay, species of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis were used, cultivated in RPMI medium with 10% SFBi. The 50% inhibitory concentration (IC50) of voriconazole was evaluated by the inhibition of promastigotes exposed to voriconazole at concentrations of 6.25 to 200 µg.mL-1 diluted in culture medium and fluconazole at 25 to 400 µg.mL-1. In the experiment, parasites plus culture medium and pentamidine isethionate at 3 µg.mL-1 were used as controls for 24, 48 and 72 h in triplicate. The concentrations of voriconazole used in the test showed antileishmanial activity against promastigotes of both Leishmania species, with an IC50 of 5.34 µg.mL-1 for L. amazonensis and 5.66 µg.mL-1 for L. guyanensis. Therefore, the study showed that off-label voriconazole presented better results than fluconazole against Leishmania species, in addition to showing better enzymatic coupling of new targets.

Clinical features and treatment of rosacea

Background: Rosacea is a common facial dermatological disease characterized by central erythema and flushing. It is more common in females than males, with a prevalence of approximately 5.5% in the global population and 2.4% among all dermatological outpatients. In 2002, the National Rosacea Society Expert Committee suggested a subtype-based standardized classification system. The most common subtype of rosacea is erythematotelangiectatic rosacea (ETR), followed by papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea.Current Concepts: Rosacea is characterized by hyperactive innate and neurovascular immune reactions, which lead to altered adaptive immune reactions and hyperreactive inflammation. In 2017, the National Rosacea Society Expert Committee developed a phenotype-based classification system. The diagnostic features include persistent centrofacial erythema and phymatous changes. ETR is associated with sensitive skin and may have a debilitating psychological impact, often leading to psychological conditions such as depression and anxiety. Doxycycline and minocycline are considered the gold-standard oral treatments for rosacea. Topical ivermectin and metronidazole are commonly used to treat PPR. Low-dose isotretinoin is an alternative to avoid long-term chronic antibiotic use. Carvedilol and propranolol are off-label medications used to reduce persistent facial flushing and erythema in rosacea. Some alpha-adrenergic receptor agonists have also been approved for the treatment of persistent erythema in rosacea.Discussion and Conclusion: Rosacea exhibits multiple phenotypic manifestations. The treatment approach is individualized for each patient through the customization of multimodal treatments, including the avoidance of trigger factors and the assessment of comorbid diseases.

Update on Pediatric Anti-obesity Medications-Current Landscape and Approach to Prescribing.

To review the current medical therapies available for treatment of obesity in children and adolescents less than 18years old in the United States and outline the approach to their use. Obesity is a chronic disease with increasing prevalence in children and adolescents in the United States. Over the past few years, more FDA-approved medical treatments for obesity, such as GLP-1 receptor agonists, have emerged for patients less than 18years old. Furthermore, there are medications with weight loss effects that can be used off-label for obesity in pediatric patients. However, access to many of these medications is limited due to age restrictions, insurance coverage, and cost. Medical options are improving to provide treatment for obesity in pediatric populations. FDA and off-label medications should be considered when appropriate to treat children and adolescents with obesity. However, further studies are needed to evaluate the efficacy and long-term safety of FDA-approved and off-label medications for obesity treatment in pediatric patients.

Current issues related to the off-label use of drugs and their potential solutions

Relevance. Off-label use of medications is a common practice in clinical settings. To address the growing interest in this issue, the International Society for Pharmacoepidemiology (ISPE) has developed new general guidelines for off-label prescribing in clinical practice that emphasize the importance of evidence-based medicine and promote transparent communication between healthcare professionals and patients.Objective. The aim of this work was to analyze and present key trends for optimizing off-label prescribing decisions based on the ISPE recommendations (2023).Results. The report highlights five main recommendations: seeking strong scientific evidence, including the use of real-world data; using expert knowledge to evaluate and summarize evidence; developing recommendations with rigorous consistency; aligning the use of off-label medications with research; and strengthening collaboration among regulators, researchers, clinicians, and the pharmaceutical industry.Conclusions. A comprehensive approach is required to address the problem of off-label use of medicines. Implementation of these initiatives will reduce the risks associated with off-label use, generate sustainable scientific evidence, and improve the quality of patient care.

Barriers and facilitators to guideline for the management of pediatric off-label use of drugs in China: a qualitative descriptive study

BackgroundDespite being a global public health concern, there is a research gap in analyzing implementation strategies for managing off-label drug use in children. This study aims to understand professional health managers’ perspectives on implementing the Guideline in hospitals and determine the Guideline’s implementation facilitators and barriers.MethodsPediatric directors, pharmacy directors, and medical department directors from secondary and tertiary hospitals across the country were recruited for online interviews. The interviews were performed between June 27 and August 25, 2022. The Consolidated Framework for Implementation Research (CFIR) was adopted for data collection, data analysis, and findings interpretation to implement interventions across healthcare settings.ResultsIndividual interviews were conducted with 28 healthcare professionals from all over the Chinese mainland. Key stakeholders in implementing the Guideline for the Management of Pediatric Off-Label Use of Drugs in China (2021) were interviewed to identify 57 influencing factors, including 27 facilitators, 29 barriers, and one neutral factor, based on the CFIR framework. The study revealed the complexity of the factors influencing managing children’s off-label medication use. A lack of policy incentives was the key obstacle in external settings. The communication barrier between pharmacists and physicians was the most critical internal barrier.ConclusionTo our knowledge, this study significantly reduces the implementation gap in managing children’s off-label drug use. We provided a reference for the standardized management of children’s off-label use of drugs.

From bench to bedside: Advancing towards therapeutic treatment of vestibular schwannomas.

Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.

Treatment of Alzheimer's Disease in the New Era of Monoclonal Antibodies Against Cerebral Amyloid-β: Pharmacological Prescription and Knowledge in Argentina.

Alzheimer's disease (AD) presents a significant global health challenge. Understanding the current and upcoming treatment landscape is crucial for effectively managing patients. The aim of this study was to assess the pattern of prescription and knowledge about new therapies by physicians who treat AD patients in Argentina. A cross- sectional and analytic study was conducted. A survey was elaborated about pharmacological treatment in AD. Statistical analysis of answers of specialists in cognitive disorders (SCD), non-specialists in cognitive disorders (NSCD), recommended treatment, non-recommended treatment (NRT), and off-label treatment was performed. 155 physicians answered the survey. A 19.35%prescribed at least one NRT for dementia. 78.06%prescribed at least an off-label treatment or an NRT for mild cognitive impairment (MCI). 31%would prescribe monoclonal antibodies (MABs) against cerebral amyloid-β (Aβ) to AD patients, and 42.6%responded that they were not aware of any adverse effect of these. Quetiapine was the most frequent treatment for psychotic symptoms (88.4%) and escitalopram (32.3%) for apathy. A 70%of potential prescribers of MABs (n = 100) would request biomarkers of cerebral Aβ in the initial assessment. There were significant differences between the responses of SCD and NSCD regarding the prescription of MABs (52.17%versus 23.08, respectively) and knowledge about adverse events (76.09%versus 38.46%, respectively). A considerable percentage of physicians indicated NRT and off-label medication in MCI and dementia. In Argentina, there are many physicians who would indicate a MABs for AD, but many are not completely aware of its safety profile.