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Aminopiridinas , Benzamidas , Ciclopropanos , Dermatitis Atópica , Inhibidores de Fosfodiesterasa 4 , Humanos , Dermatitis Atópica/tratamiento farmacológico , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Aminopiridinas/administración & dosificación , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Ciclopropanos/uso terapéutico , Ciclopropanos/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/farmacología , Ciclopropanos/farmacocinética , Benzamidas/efectos adversos , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Crema para la Piel/administración & dosificación , Administración CutáneaAsunto(s)
Acetatos , Antiasmáticos , Asma , Ciclopropanos , Quinolinas , Sulfuros , Humanos , Asma/tratamiento farmacológico , Sulfuros/efectos adversos , Ciclopropanos/efectos adversos , Acetatos/efectos adversos , Acetatos/uso terapéutico , Antiasmáticos/efectos adversos , Quinolinas/efectos adversos , Niño , Masculino , Problema de ConductaRESUMEN
Purpose: This study evaluated the long-term safety of roflumilast in patients with chronic obstructive pulmonary disease or chronic bronchitis using electronic healthcare databases from Germany, Norway, Sweden, and the United States (US). Patients and Methods: The study population consisted of patients aged ≥40 years who had been exposed to roflumilast and a matched cohort unexposed to roflumilast. The matching was based on sex, age, calendar year of cohort entry date (2010-2011, 2012, or 2013), and a propensity score that included variables such as demographics, markers of chronic obstructive pulmonary disease (COPD) severity and morbidity, and comorbidities. In comparison to the unexposed matched cohort (never use), three exposure definitions were used for the exposed matched cohort: ever use, use status (current, recent, past use), and cumulative duration of use. The main outcome was 5-year all-cause mortality. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CI). Results: 112,541 unexposed and 23,239 exposed patients across countries were included. Some variables remained unbalanced after matching, indicating higher COPD disease severity among the exposed patients. Adjusted HRs of 5-year all-cause mortality for "ever use" of roflumilast, compared to "never use", were 1.12 (95% CI, 1.08-1.17) in Germany, 1.00 (95% CI, 0.92-1.08) in Norway, 0.98 (95% CI, 0.92-1.04) in Sweden, and 1.16 (95% CI, 1.12-1.20) in the US. Compared to never users, there was a decrease in 5-year mortality risk observed among "current users" in Germany (HR: 0.93, 95% CI: 0.88-0.98), Norway (HR: 0.77, 95% CI: 0.67-0.87), and Sweden (HR: 0.80, 95% CI: 0.73-0.88). Conclusion: There was no observed increase in 5-year mortality risk with the use of roflumilast in Sweden or Norway. A small increase in 5-year mortality risk was observed in Germany and the US in the ever versus never comparison, likely due to residual confounding by indication.
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Aminopiridinas , Benzamidas , Ciclopropanos , Bases de Datos Factuales , Inhibidores de Fosfodiesterasa 4 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Masculino , Femenino , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Benzamidas/efectos adversos , Benzamidas/uso terapéutico , Persona de Mediana Edad , Anciano , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Factores de Riesgo , Estados Unidos/epidemiología , Bronquitis Crónica/tratamiento farmacológico , Bronquitis Crónica/mortalidad , Bronquitis Crónica/epidemiología , Medición de Riesgo , Alemania , Adulto , Suecia/epidemiología , Anciano de 80 o más AñosRESUMEN
INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles. MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment. RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects. DISCUSSION: Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs. CONCLUSION: Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice.
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Aminopiridinas , Benzamidas , Ciclopropanos , Psoriasis , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Aminopiridinas/uso terapéutico , Psoriasis/tratamiento farmacológico , Ciclopropanos/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/uso terapéutico , Benzamidas/efectos adversos , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Resultado del Tratamiento , Administración Tópica , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Administración Cutánea , Resorcinoles , EstilbenosAsunto(s)
Aminopiridinas , Benzamidas , Ciclopropanos , Humanos , Aminopiridinas/efectos adversos , Aminopiridinas/administración & dosificación , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Femenino , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Crema para la Piel/administración & dosificación , Crema para la Piel/efectos adversos , Trastornos por Fotosensibilidad/tratamiento farmacológico , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/inducido químicamente , Masculino , Persona de Mediana EdadRESUMEN
Severe alopecia areata (AA) is a nonscarring hair loss for immune disorder and SALT score ≥ 50%. The guidelines for managing patients with severe AA suggest treatments: systemic steroids, JAK inhibitors, and contact immunotherapy. However, there is a lack of evidence indicating the superiority of one treatment over another. Therefore, this study aimed to identify the most effective treatment for severe AA through network meta-analysis. Following the PRISMA guidelines, we conducted a network meta-analysis. The literature search was retrieved across four databases. The Cochrane 5.1 risk of bias assessment tool and ROBINS-I tool assessed quality of the included studies. Subsequently, efficacy and safety comparisons among the three treatments were conducted using Stata 14.0 on account of the frequency method. The SUCRA rank indicated that oral dexamethasone (95.9%) > diphenylcyclopropenone(DPCP) (74.5%) > oral ritlecitinib (62.6%) > oral baricitinib (46.9%) > squaric acid dibutyl ester(SADBE) (20.1%) > placebo (0.0%) from high to low in the aspect of improving efficacy. As for safety, placebo(88.4%) > oral ritlecitinib (86.5%) > oral baricitinib (62.1%) > SADBE (37.0%) > oral dexamethasone(22.3%) > DPCP(3.8%) in the aspect of decreasing adverse events. Oral dexamethasone and DPCP showed superior efficacy compared to oral ritlecitinib and oral baricitinib. However, in terms of safety, oral ritlecitinib was preferable. Some adverse events associated with oral dexamethasone and DPCP were intolerable to patients, whereas those related to oral ritlecitinib and oral baricitinib were more manageable. Overall, ritlecitinib and baricitinib remain promising drugs in the future treatment of severe AA.
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Alopecia Areata , Inhibidores de las Cinasas Janus , Metaanálisis en Red , Humanos , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificación , Resultado del Tratamiento , Administración Oral , Purinas/administración & dosificación , Purinas/efectos adversos , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Índice de Severidad de la Enfermedad , PirazolesAsunto(s)
Acetatos , Ciclopropanos , Psicosis Inducidas por Sustancias , Quinolinas , Sulfuros , Adolescente , Niño , Humanos , Acetatos/efectos adversos , Acetatos/uso terapéutico , Asma/tratamiento farmacológico , Ciclopropanos/efectos adversos , Psicosis Inducidas por Sustancias/etiología , Quinolinas/efectos adversos , Sulfuros/efectos adversosRESUMEN
Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.
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Antivirales , Hepacivirus , Sofosbuvir , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , África Central , África Occidental , Ácidos Aminoisobutíricos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Bencimidazoles/uso terapéutico , Bencimidazoles/efectos adversos , Benzopiranos , Carbamatos/uso terapéutico , Ciclopropanos/uso terapéutico , Ciclopropanos/efectos adversos , Quimioterapia Combinada , Estudios de Factibilidad , Fluorenos/uso terapéutico , Fluorenos/efectos adversos , Genotipo , Hepacivirus/genética , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Prolina/uso terapéutico , Quinoxalinas , Ribavirina/uso terapéutico , Ribavirina/efectos adversos , Sofosbuvir/uso terapéutico , Sofosbuvir/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38ß MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics.
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Distrofia Muscular Facioescapulohumeral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Método Doble Ciego , Piridinas/efectos adversos , Piridinas/uso terapéutico , Resultado del TratamientoAsunto(s)
Dermatitis Seborreica , Fármacos Dermatológicos , Humanos , Dermatitis Seborreica/diagnóstico , Dermatitis Seborreica/tratamiento farmacológico , Aminopiridinas/efectos adversos , Benzamidas , Ciclopropanos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Resultado del Tratamiento , Administración TópicaRESUMEN
El alelo HLA B*57:01 es un marcador genético asociado con la hipersensibilidad al fármaco anti-retroviral abacavir (ABC) y su frecuencia en la población peruana todavía es desconocida. El objetivo fue identificar el alelo HLA B*57:01 en una población militar de Lima, Perú. Se reclutaron 43 personas viviendo con VIH (PVV) quienes aceptaron participar a través de un consentimiento informado. La detección del alelo HLA B*57:01 se realizó mediante RPC en tiempo real (RT-PCR). Asimismo, se determinó la carga viral (CV), el recuento de linfocitos CD4 y la genotipificación del VIH. Se identificaron dos casos positivos al alelo HLA B*57:01 (4,7%). Además, uno de ellos presentó múltiples mutaciones de resistencia a los anti-retrovirales (ARV), incluyendo ABC. Se demostró por primera vez en el Perú la presencia del alelo HLA B*57:01.
The HLA B*57:01 allele is a genetic marker associated with hypersensitivity to the antiretroviral Abacavir (ABC) and its frequency in the Peruvian population is still unknown. The objective was to identify the HLA B*57:01 allele in a military population from Lima, Peru. Forty three people living with HIV (PLWH) were recruited, who agreed to participate through informed consent. Detection of the HLA B*57:01 allele was performed by real-time PCR (RT-PCR). Likewise, viral load (VL), CD4 lymphocyte count and HIV genotyping were determined. Two cases positive for the HLA B*57:01 allele (4.7%) were identified. In addition, one of them had multiple resistance mutations to antiretrovirals (ARVs), including ABC. The presence of the HLA B*57:01 allele was demonstrated for the first time in Peru.
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Humanos , Masculino , Persona de Mediana Edad , Infecciones por VIH/genética , Fármacos Anti-VIH/efectos adversos , Hipersensibilidad a las Drogas/genética , Personal Militar , Perú , Antígenos HLA-B/genética , Marcadores Genéticos , Infecciones por VIH/tratamiento farmacológico , VIH/genética , Recuento de Linfocito CD4 , Carga Viral/genética , Predisposición Genética a la Enfermedad , Ciclopropanos/efectos adversos , Hipersensibilidad a las Drogas/inmunología , Alelos , Reacción en Cadena en Tiempo Real de la Polimerasa , GenotipoRESUMEN
BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.
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Aminopiridinas , Benzamidas , Ciclopropanos , Inhibidores de Fosfodiesterasa 4 , Psoriasis , Índice de Severidad de la Enfermedad , Crema para la Piel , Humanos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Psoriasis/tratamiento farmacológico , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Benzamidas/efectos adversos , Benzamidas/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Resultado del Tratamiento , Crema para la Piel/administración & dosificación , Crema para la Piel/efectos adversos , Enfermedad Crónica , Anciano , Esquema de Medicación , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.
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Aminopiridinas , Benzamidas , Ciclopropanos , Inhibidores de Fosfodiesterasa 4 , Psoriasis , Pérdida de Peso , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Ciclopropanos/administración & dosificación , Ciclopropanos/uso terapéutico , Ciclopropanos/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Benzamidas/administración & dosificación , Benzamidas/uso terapéutico , Benzamidas/efectos adversos , Adulto , Administración Oral , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Pérdida de Peso/efectos de los fármacos , Método Doble Ciego , Peso Corporal/efectos de los fármacos , Anciano , Presión Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Índice de Severidad de la EnfermedadRESUMEN
IMPORTANCE: Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking. OBJECTIVE: This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population. DATA SOURCES: PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA. STUDY SELECTION: Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children. DATA EXTRACTION AND SYNTHESIS: Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2). RESULTS: 17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %). CONCLUSIONS AND RELEVANCE: The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.
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Ciclopropanos , Metaanálisis en Red , Apnea Obstructiva del Sueño , Sulfuros , Humanos , Apnea Obstructiva del Sueño/tratamiento farmacológico , Niño , Ciclopropanos/uso terapéutico , Ciclopropanos/efectos adversos , Sulfuros/uso terapéutico , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Acetatos/uso terapéutico , Acetatos/efectos adversos , Furoato de Mometasona/uso terapéutico , Furoato de Mometasona/administración & dosificación , Teorema de BayesRESUMEN
Background: The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD). However, roflumilast has shown frequent adverse drug reactions (ADRs). This study was performed to investigate the dosing strategy that will improve adherence to roflumilast in COPD. Methods: We conducted a systematic review and meta-analysis using PubMed, Embase, and Cochrane Central Register. The dosing strategy for roflumilast was classified into a dose-escalation group and a low-dose group. We investigated clinical outcomes according to dosing strategy. Results: Five clinical trials involving 2424 patients were included. Both the dose-escalation and the low-dose groups showed a decrease in discontinuation rate compared to the standard dosing group for roflumilast (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67-0.97; P = 0.02 and RR, 0.62; 95% CI, 0.48-0.80; P < 0.01, respectively). In the two strategies, the pooled proportions of discontinuation were 27.9% and 11.7%, respectively. Although the pooled proportion of any ADR was not statistically decreased in the two strategies, diarrhea was significantly reduced in the low-dose group compared to the standard group (RR, 0.58; 95% CI, 0.42-0.82; P < 0.01). The pooled incidence of acute exacerbations was similar between the low-dose and the standard groups (22.9% and 20.1%, respectively; P = 0.27). Conclusion: Our findings show that the two alternative dosing strategies might have the benefit of improving adherence to roflumilast in COPD. Further large-scale trials are required to support our findings.
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Aminopiridinas , Benzamidas , Ciclopropanos , Cumplimiento de la Medicación , Inhibidores de Fosfodiesterasa 4 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Benzamidas/uso terapéutico , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Resultado del Tratamiento , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Anciano , Femenino , Persona de Mediana Edad , Masculino , Factores de RiesgoAsunto(s)
Fármacos Dermatológicos , Psoriasis , Humanos , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Aminopiridinas/efectos adversos , Benzamidas/efectos adversos , Ciclopropanos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Resultado del Tratamiento , Administración Tópica , Administración Cutánea , Índice de Severidad de la EnfermedadRESUMEN
Various therapeutic options are available for verruca. While physical destruction may be associated with scarring, immunotherapy may be effective in treating warts through stimulating body immune response. The objective of the study was to compare the efficacy, safety, and outcome of Candida antigen vs diphencyprone (DPCP) in the treatment of warts. Fifty patients were randomly assigned to receive either intralesional Candida antigen every 3 weeks or weekly DPCP application. Both treatments were applied only to the mother wart. Lesions' clearance and associated side effects were observed up to 4 weeks after treatment. Two blinded physicians evaluated photos of warts before and 4 weeks after the end of treatment. Both modalities granted wart clearance and/or improvement with no statistically significant difference; however, Candida antigen was significantly better in clearing adjacent untreated warts (p = 0.046). Fewer side effects were observed among the Candida antigen group. The response was duration associated in the Candida groups only. Intralesional Candida antigen injection and DPCP treatments for warts yielded improvement with superiority of Candida injection in eradicating distant lesions and fewer side effects. A shorter wart duration may be associated with a better therapeutic response with Candida antigen.
Asunto(s)
Antígenos Fúngicos , Candidiasis , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vacunas , Verrugas , Humanos , Antígenos Fúngicos/administración & dosificación , Antígenos Fúngicos/efectos adversos , Candida , Inmunoterapia/efectos adversos , Inyecciones Intralesiones , Resultado del Tratamiento , Vacunas/administración & dosificación , Vacunas/efectos adversos , Verrugas/terapia , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Candidiasis/terapiaRESUMEN
Abacavir (ABC)-induced hypersensitivity (AHS) is strongly associated with human leukocyte antigen (HLA)-B*57 : 01 expression. Previous studies have demonstrated the feasibility of applying the HLA-transgenic mouse model in this context. ABC-induced adverse reactions were observed in HLA-B*57 : 01 transgenic (B*57 : 01-Tg) mice. Moreover, regulating immune tolerance could result in severe AHS that mimics symptoms observed in the clinical setting, which were modeled in CD4+ T cell-depleted programmed death-1 receptor (PD-1) knockout B*57 : 01-Tg (B*57 : 01-Tg/PD-1-/-) mice. Here, we aimed to examine whether thymus and activation-regulated chemokine (TARC)/CCL17 level can be used as a biomarker for AHS. Serum TARC levels increased in HLA-B*57 : 01-transgenic mice following oral administration of ABC; this increase was associated with the severity of skin toxicity. In ABC-fed CD4+ T cell-depleted B*57 : 01-Tg/PD-1-/- mice, TARC was detected in the epidermal keratinocytes of the ear. Skin toxicity was characterized by the infiltration of CD8+ T cells partially expressing C-C chemokine receptor type 4, which is the primary receptor for TARC. In vivo TARC neutralization effectively alleviated the symptoms of ear skin redness and blood vessel dilatation. Moreover, TARC neutralization suppressed the infiltration of CD8+ T cells to the ear skin but did not affect the ABC-induced adaptive immune response. Therefore, TARC was involved in ABC-induced skin toxicity and contributed to the recruitment of CD8+ T cells to skin. This evidence suggests that serum TARC level may be a functional biomarker for AHS.
Asunto(s)
Linfocitos T CD8-positivos , Quimiocina CCL17 , Dermatitis Atópica , Animales , Linfocitos T CD8-positivos/inmunología , Quimiocina CCL17/genética , Quimiocinas , Ciclopropanos/efectos adversos , Didesoxiadenosina/efectos adversos , Didesoxiadenosina/análogos & derivados , Antígenos HLA-B/genética , Humanos , Ratones , Ratones Transgénicos , Receptor de Muerte Celular Programada 1RESUMEN
Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.