RESUMEN
Atopic dermatitis (AD) is a heterogeneous inflammatory condition involving multiple immune pathways mediated by pathogenic T cells. OX40 Ligand (OX40L) and OX40 are co-stimulatory immune checkpoint molecules that regulate effector and memory T cell activity and promote sustained immune responses in multiple immunological pathways, including Th2, Th1, Th17 and Th22. As such, OX40L/OX40 signalling between antigen-presenting cells (APCs) and activated T cells post-antigen recognition promotes pathogenic T cell proliferation and survival. Under inflammatory conditions, OX40L is upregulated on APCs, enhancing the magnitude of antigen-specific T cell responses and secretion of proinflammatory cytokines. In AD, OX40L/OX40 signalling contributes to the amplification and chronic persistence of T-cell mediated inflammation. Recent therapeutic success in clinical trials has highlighted the importance of the OX40L/OX40 axis as a promising target for the treatment of AD. Here we discuss the many factors that are involved in the expression of OX40L and OX40, including the cytokine milieu, antigen presentation, the inflammatory environment in AD, and the therapeutic direction influenced by this co-stimulatory pathway.
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Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.
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Urticaria Crónica , Omalizumab , Humanos , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/diagnóstico , Omalizumab/uso terapéutico , Omalizumab/administración & dosificación , Antagonistas de los Receptores Histamínicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/uso terapéutico , Ciclosporina/uso terapéutico , Ciclosporina/administración & dosificación , Urticaria/tratamiento farmacológico , Urticaria/diagnósticoRESUMEN
BACKGROUND/OBJECTIVES: Disease improvement for difficult-to-control pediatric atopic dermatitis may be more challenging to achieve when directed by single specialties due to disjointed and conflicting dialogue with patients. METHODS: The Multidisciplinary Atopic Dermatitis Program (MADP) was developed through collaborations with the Rady Children's Hospital and UC San Diego Health Divisions of Dermatology, Allergy & Immunology and Clinical Pharmacy, to create team-based evaluation and management of children and adolescents with atopic dermatitis (AD). The MADP allows concurrent, comprehensive evaluations by multiple specialists to develop treatment plans. The program includes extensive patient education to support shared decision making, incorporating patient and family's perspectives along with those of clinical experts into their care. Objective severity measures and patient reported outcome data were collected, along with assessment of patient and family satisfaction with the MADP. RESULTS: Data showed significant improvement in AD severity as assessed by providers, patients and families by the first follow-up visit. BSA mean percentage decreased by up to 56% by the 7th visit, and pruritus (NRS), CLDQI and POEM mean scores decreased by more than 4 points, 12 points, and over 11 points, respectively. After management was initiated in the MADP, 72.73% of patients achieved an EASI 50 and 47.73% achieved an EASI 75 from a baseline mean of 21.7. Patients who continued in clinic beyond the second visit showed further clinically significant decreases in disease measures. CONCLUSIONS: The multidisciplinary approach shows success in the treatment of difficult-to-control AD patients with improvements in clinician and patient reported outcome measures.
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Dermatitis Atópica , Adolescente , Humanos , Niño , Dermatitis Atópica/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Prurito , Medición de Resultados Informados por el Paciente , Hospitales Pediátricos , Resultado del Tratamiento , Calidad de VidaRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
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Agammaglobulinemia , Síndromes de Inmunodeficiencia , Linfopenia , Neutropenia , Verrugas , Humanos , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/genética , Verrugas/diagnóstico , Verrugas/epidemiología , Verrugas/genética , Agammaglobulinemia/genética , Receptores CXCR4/genética , Neutropenia/genética , Linfopenia/complicaciones , Progresión de la EnfermedadRESUMEN
A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.
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Infecciones Bacterianas , Síndromes de Inmunodeficiencia , Humanos , Estudios Prospectivos , Infusiones Subcutáneas , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Resultado del Tratamiento , Inmunoglobulinas Intravenosas/uso terapéuticoRESUMEN
OBJECTIVE: To review recent trends in the development of targeted small molecule drugs (SMDs) for the treatment of immunologically driven disorders, including atopic dermatitis, rheumatoid arthritis, and hereditary angioedema. DATA SOURCES: Data sources included peer-reviewed published literature from the PubMed database, published abstracts from scientific and medical meetings, and medication information from the Drugs@FDA database. STUDY SELECTIONS: Articles with primary or retrospective trial results, articles with patient or physician survey results, articles providing expert perspectives, and commentary on chronic immunologic disorders, Food and Drug Administration package inserts, and abstracts from scientific meetings were selected. RESULTS: Targeted biological therapies have greatly improved response rates and symptom relief for patients with long-term immunologically driven disorders over the past 2 decades. However, recent advances in the understanding of molecular pathways involved in the pathogenesis of these disorders have led to the development of novel targeted SMDs, such as tofacitinib and berotralstat, that can be delivered orally or topically. Few head-to-head studies that compare the safety and efficacy of biologics to SMDs in immunologically driven disorders exist, although some studies suggest that oral and topical modes of administration are preferred by patients and may improve patient quality of life over time. CONCLUSION: Scientific advances have led to an increase in the development of targeted SMDs for the treatment of chronic immunologic disorders, which may revolutionize the management of these diseases. Head-to-head studies and real-world evidence are needed to fully compare treatment attributes between biologics and SMDs, including safety, efficacy, adherence, impact on quality of life, and cost-effectiveness.
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Angioedemas Hereditarios , Artritis Reumatoide , Dermatitis Atópica , Angioedemas Hereditarios/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Dermatitis Atópica/tratamiento farmacológico , Desarrollo de Medicamentos/tendencias , Humanos , Preparaciones Farmacéuticas , Calidad de Vida , Estudios RetrospectivosRESUMEN
Atopic dermatitis (AD) is a very common skin disease associated with substantial burdens on patient health and quality of life. Knowledge regarding the pathogenesis of AD has expanded within recent years, leading to novel and efficacious therapeutic agents. Similarly, our knowledge of the impact of AD on patient's mental and physical health has also expanded. This review summarizes updates on the evolution, comorbidities, and therapeutic options of AD. AD is associated with increased cardiovascular risk, allergic diseases, and adverse mental health outcomes. Topical and systemic therapeutics have drastically altered the landscape of AD therapy in recent years.
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Dermatitis Atópica , Calidad de Vida , Comorbilidad , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , HumanosRESUMEN
BACKGROUND: Effectiveness of asthma treatment, including biologics, may be different in patients with higher body mass index (BMI). OBJECTIVE: To evaluate response to omalizumab (dosed by serum immunoglobulin E level and weight) by BMI category. METHODS: Pooled data from 2 randomized, double-blind, placebo-controlled studies of adults with moderate-to-severe allergic asthma were analyzed by BMI category (<25 kg/m2 [normal or underweight], n = 397; 25 to <30 kg/m2 [overweight], n = 330; ≥ 30 kg/m2 [obese], n = 268). Placebo-adjusted exacerbation rate reductions were evaluated by Poisson regression modeling. Changes from baseline in forced expiratory volume in 1 second, beclomethasone dipropionate (BDP) dose, Total Asthma Symptom Score, and Asthma Quality of Life Questionnaire were evaluated by analysis of covariance. RESULTS: Greater placebo-adjusted exacerbation rate reductions (95% confidence interval) were observed with increasing BMI (normal or underweight, -37.4% [-69.0% to 26.8%]; overweight, -52.7% [-78.4% to 3.7%]; obese, -71.9% [-86.9% to -39.5%]). There were no differences in forced expiratory volume in 1 second improvement between BMI categories at week 16 (normal or underweight, 76.2 [5.3-147.1] mL; overweight, 98.1 [13.9-182.4] mL; obese, 69.1 [-18.9 to 157.2] mL). No differences in BDP dose reduction (µg) were noted between BMI categories (normal or underweight, 23.0 [15.7-30.3]; overweight, 22.5 [13.5-31.5]; obese, 16.6 [5.8-27.3]). Fewer patients in the higher BMI categories eliminated BDP use. There were trends for smaller improvements with higher BMI in Total Asthma Symptom Score (normal/underweight, -0.52 [-0.82 to -0.22]; overweight, -0.50 [-0.80 to -0.20]; obese, -0.39 [-0.77 to 0.00]) and Asthma Quality of Life Questionnaire (normal or underweight, 0.34 [0.16-0.52]; overweight, 0.34 [0.13-0.55]; obese, 0.15 [-0.08 to 0.39]). CONCLUSION: Omalizumab provides benefit to patients with moderate-to-severe allergic asthma, regardless of BMI. TRIAL REGISTRATION: Studies 008/009 were conducted before clinical trial registration was required, and therefore clinical trial registration numbers are not available.
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Antiasmáticos , Asma , Adulto , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Beclometasona/farmacología , Beclometasona/uso terapéutico , Índice de Masa Corporal , Método Doble Ciego , Volumen Espiratorio Forzado , Humanos , Obesidad/tratamiento farmacológico , Omalizumab/farmacología , Omalizumab/uso terapéutico , Sobrepeso , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Delgadez/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Background: Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. Objective: To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome. Methods: A 5-year retrospective two-arm cohort study explored patients on asthma and not on ICS relative to patients with asthma who were on varying doses of ICS (low, medium, and high) and attributes such as body mass index (BMI) trajectory and prescription of antihypertensive, antidiabetic, and cholesterol-lowering medications. Results: A total of 229 subjects with asthma were in the control cohort, and 215 subjects with asthma were in the ICS cohort. The ICS cohort was subdivided into individuals on low- (n = 88), medium- (n = 107), or high- (n = 20) dose ICS throughout the 5-year study period. For every 1-year increase in time, the BMI in the high-dose ICS group increased at a rate of 0.25 kg/m² when compared with the subjects in the control group after controlling for age and gender. Also, for every 1-year increase in time, the BMI of those on medium-dose ICS increased by 0.06 kg/m² compared with those in the control group after controlling for age and gender. The subjects on ICS also had a statistically increased risk of being prescribed antihypertensive, antidiabetic, and cholesterol-lowering medications. Conclusion: ICS use in the subjects with asthma was associated with a dose-dependent risk of increasing BMI trajectories over time and an increased requirement for antidiabetic and cholesterol-lowering medications. One possible conclusion from this study is that long-term medium- and high-dose ICS have the potential to induce systemic effects.
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Antiasmáticos , Asma , Síndrome Metabólico , Administración por Inhalación , Corticoesteroides/efectos adversos , Antiasmáticos/efectos adversos , Antihipertensivos/uso terapéutico , Asma/tratamiento farmacológico , Asma/epidemiología , Colesterol/uso terapéutico , Estudios de Cohortes , Humanos , Hipoglucemiantes/uso terapéutico , Sistema Hipotálamo-Hipofisario , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Sistema Hipófiso-Suprarrenal , Estudios RetrospectivosRESUMEN
BACKGROUND: To diagnose and adequately treat allergies, identification of sensitizing allergens is crucial. Skin prick or serum immunoglobulin E testing determines sensitization to potential allergens. Consensus varies regarding degree of cross-reactivity between aeroallergens. OBJECTIVE: To quantify correlations between aeroallergen skin prick test results. METHODS: A total of 11,832 patients' quantitative skin prick test results and basic characteristics were obtained from a tertiary academic center's electronic medical record and deidentified. Data were analyzed using Spearman's rank correlation coefficients to detect nonlinear associations between wheal sizes of skin prick test results. RESULTS: The highest correlation among grasses was 0.903 (fescue and red top). Of note, 13 more grass pairs had correlation more than 0.8, and 19 had correlation between 0.7 and 0.8. The Northern grass comparative results are from a satellite clinic that tested more grasses than the main clinic, in which only Kentucky blue and Bermuda were tested (correlation 0.768; n = 9348). Highest correlation among weeds was 0.74 (lambs quarter and pigweed). In addition, 6 more weed pairs had correlation more than 0.7. Highest correlation among trees was 0.724 (palm and alder) and 6 more tree pairs had correlation more than 0.7. Highest correlation among molds was 0.711 (Helminthosporium and Epicoccum). Dust mite correlation between Dermatophagoides farinae and Dermatophagoides pteronyssinus was 0.848 (n = 10,022). CONCLUSION: This study confirmed the expected high degrees of correlation not only between skin prick test results of related environmental allergens but also between less closely related Northern grasses and Bermuda grass. This has implications for simplification of testing and immunotherapy protocols in the future.
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Alérgenos/inmunología , Hipersensibilidad/diagnóstico , Hipersensibilidad/inmunología , Adolescente , Adulto , Animales , Niño , Preescolar , Reacciones Cruzadas/inmunología , Femenino , Humanos , Masculino , Pyroglyphidae/inmunología , Pruebas Cutáneas/métodos , Adulto JovenRESUMEN
PURPOSE OF REVIEW: There is an emerging body of research on targeted biologic therapies for the treatment of severe inflammatory nasal disorders, especially chronic rhinosinusitis with nasal polyposis (CRSwNP). This paper will evaluate the efficacy of biologic therapies for severe nasal inflammation by summarizing key preclinical trials of biologics for animal models of allergic rhinitis and the recent phase 2 and 3 clinical trials of biologic therapies for CRSwNP. RECENT FINDINGS: Biologics that target the IL-4 receptor (dupilumab), IgE (omalizumab), and IL-5 (mepolizumab, reslizumab, and benralizumab) in patients with CRSwNP have shown improvement of various metrics including Sino-Nasal Outcome Test (SNOT-22) scores, Nasal Polyp Scores (NPS), Nasal Congestion Scores (NCS), and Lund-Mackay sinus opacification scores. The efficacy demonstrated through the dupilumab phase 3 trials (LIBERTY NP SINUS-24 and SINUS-52) led to approval of the first biologic for the treatment of CRSwNP. Phase 3 trials for omalizumab (POLYP 1 and 2) and mepolizumab (SYNAPSE study) and post hoc analyses of phase 3 asthma studies for reslizumab and benralizumab have also demonstrated positive results for the use of biologics for patients with CRSwNP. Future efficacy studies and risk/benefit and cost analyses of these biologics and other cytokine targets for allergic rhinitis with and without nasal polyposis need to be performed.
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Pólipos Nasales , Rinitis Alérgica , Rinitis , Sinusitis , Terapia Biológica , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Omalizumab , Rinitis Alérgica/tratamiento farmacológico , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológicoRESUMEN
Background: Primary immunodeficiency diseases (PIDD) consist of a heterogeneous group of disorders characterized by various aspects of immune dysregulation. Although the most universally recognized manifestation of PIDD is an increased susceptibility to infections, there is a growing body of evidence that patients with PIDD often have a higher incidence of lung disease, autoimmunity, autoinflammatory disorders, and malignancy. Objective: The purpose of this study was to better understand the noninfectious complications of PIDD by determining the comorbid disease prevalence across various age groups, genders, and immunoglobulin replacement types compared with the general population. Methods: A large U.S. insurance claims database was retrospectively analyzed for patients who had a diagnosis of PIDD and who had received intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG). The prevalences of 31 different comorbid conditions in the Elixhauser comorbidity index were compared among the 3125 patients in the PIDD population to > 37 million controls separated by gender and by 10-year age cohorts. Results: In the PIDD population, statistically significantly higher comorbid diagnoses included chronic obstructive pulmonary disease-asthma in 51.5%, rheumatoid disease in 14%, deficiency anemia in 11.8%, hypothyroidism in 21.2%, lymphoma in 16.7%, neurologic disorders in 9.7%, arrhythmias in 19.9%, electrolyte disorders in 23.6%, coagulopathies in 16.9%, and weight loss in 8.4%. Conclusion: PIDD that require immunoglobulin replacement are associated with an increased risk of numerous comorbid conditions that affect morbidity and mortality. Recognition and increased awareness of these noninfectious complications can allow for better monitoring, care coordination, targeted treatments, and improved prognosis.
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Factores de Edad , Inmunoglobulinas Intravenosas/uso terapéutico , Enfermedades de Inmunodeficiencia Primaria/terapia , Factores Sexuales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Lactante , Recién Nacido , Revisión de Utilización de Seguros , Masculino , Persona de Mediana Edad , Enfermedades de Inmunodeficiencia Primaria/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged 12 or more (United States) or 6 or more (European Union) years, but its long-term use in children aged 6 to 11 years has not yet been assessed. OBJECTIVE: We sought to assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6 to 11 years with severe asthma with an eosinophilic phenotype. METHODS: In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6 to 11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the previous year) received a body weight-dependent dose of subcutaneous mepolizumab of 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks. End points included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil counts (cells per microliter; secondary), and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory). RESULTS: Over 52 weeks, 30 children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No serious AEs were treatment related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations and improved asthma control across all treatment groups. CONCLUSION: Long-term safety, pharmacodynamic, and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies in adults and adolescents.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Eosinofilia/tratamiento farmacológico , Eosinófilos/inmunología , Antiasmáticos/uso terapéutico , Asma/epidemiología , Niño , Progresión de la Enfermedad , Eosinofilia/epidemiología , Femenino , Humanos , Inyecciones Subcutáneas , Interleucina-5/antagonistas & inhibidores , Recuento de Leucocitos , Masculino , Fenotipo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Patients with primary immunodeficiency disease (PIDD) and antibody deficiency require lifelong immunoglobulin replacement therapy. While both subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) replacement therapy are effective in preventing infection, patients with PIDD still experience worse health-related quality of life (hrQOL) outcomes. OBJECTIVE: Assess differences in hrQOL for PIDD patients receiving home SCIG versus IVIG. METHODS: SF-36 surveys were administered by a specialty pharmacy to 630 PIDD patients receiving home SCIG and IVIG at baseline and then every 3 months between 2014 and 2016. Results were analyzed using two-sample t tests and linear mixed effects model. Analysis was repeated for different age categories and trended over time. RESULTS: Patients receiving SCIG reported statistically significant higher energy fatigue scores (+ 9 points, p < 0.001) but lower perceived role limitations due to physical health scores (- 14 points, p < 0.001). These differences were only observed in patients > 36 years of age. There were no differences in the composite SF-36 score for patients receiving SCIG versus IVIG (+ 1, p = 0.66). Immunoglobulin-naïve patients all improved their hrQOL, but a larger improvement was seen in those initiating SCIG versus IVIG. CONCLUSION: Patients with PIDD on home IVIG versus SCIG have similar composite hrQOL scores as measured by the SF-36. In the adult population, initiating immunoglobulin replacement with SCIG may result in more hrQOL improvement compared with IVIG, although personal preferences should also be considered. CLINICAL IMPLICATIONS: Patients with PIDD on home IVIG versus SCIG have similar composite health-related quality of life scores as measured by the SF-36. Patients with primary immune-deficiency on home IVIG versus SCIG have similar composite health-related quality of life scores as measured by the SF-36. Personal preferences are important in deciding whether to treat with IVIG or SCIG.
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Fatiga/epidemiología , Cuidados de Enfermería en el Hogar/estadística & datos numéricos , Inmunoglobulinas Intravenosas/administración & dosificación , Enfermedades de Inmunodeficiencia Primaria/tratamiento farmacológico , Calidad de Vida , Adulto , Fatiga/inmunología , Femenino , Estado de Salud , Humanos , Infusiones Intravenosas/estadística & datos numéricos , Infusiones Subcutáneas/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Prioridad del Paciente , Enfermedades de Inmunodeficiencia Primaria/complicaciones , Enfermedades de Inmunodeficiencia Primaria/inmunología , Estudios Retrospectivos , Encuestas y Cuestionarios/estadística & datos numéricos , Resultado del TratamientoAsunto(s)
Asma , Niño , Humanos , Asma/tratamiento farmacológico , Instituciones de Atención AmbulatoriaRESUMEN
BACKGROUND: Although 5-grass pollen sublingual immunotherapy has a good safety profile in controlled clinical trials, additional safety information among pediatric patients in a real-world setting would be useful. OBJECTIVE: To further document the safety of 5-grass tablet among children aged 5 to 9 years with allergic rhinoconjunctivitis (ARC). METHODS: This multicenter, observational study included allergy immunotherapy-naïve 5- to 9-year-old children with grass pollen-induced ARC prescribed with 5-grass tablet daily (3-day dose escalation to 300 index of reactivity [IR]). Patients were followed up daily for safety and tolerability over the first 30 treatment days. Adverse events (AEs) and adverse drug reactions (ADRs) were analyzed descriptively. RESULTS: Three hundred seven children (mean age, 7.1 years) were enrolled. Fifty-eight percent were confirmed as polysensitized, and 36% had mild-to-moderate asthma. Of 307 patients, 233 (76%) reported AEs, and 173/307 (56%) reported ADRs, most frequently mild application-site reactions (throat irritation, oral pruritus, oral paresthesia). Sixteen of 307 (5.2%) patients withdrew because of ADRs. In 143 of 173 (83%) patients, ADRs first occurred within 1 week of starting treatment. More than half of the ADRs lasted less than 2 days, and ADRs resolved spontaneously in 161 of 173 (93%) patients. Recurrences of ADRs were reported in 45 of 173 (26%) patients and were also mainly application-site reactions. No notable differences were found in ADRs related to whether patients had asthma at inclusion. Neither epinephrine use nor admission to intensive care unit was reported. CONCLUSION: The safety profile of 5-grass tablet in pediatric ARC patients aged 5 to 9 years was consistent with safety findings in older patients, most ADRs being at the application site and mild to moderate. ClinicalTrials.gov identifier: NCT02295969; EUPAS registration number: 8104.
Asunto(s)
Conjuntivitis Alérgica/tratamiento farmacológico , Conjuntivitis Alérgica/inmunología , Poaceae/inmunología , Polen/efectos adversos , Polen/inmunología , Comprimidos/efectos adversos , Comprimidos/uso terapéutico , Administración Sublingual , Alérgenos/inmunología , Asma/inmunología , Niño , Preescolar , Desensibilización Inmunológica/métodos , Femenino , Humanos , Masculino , Rinitis Alérgica Estacional/inmunología , Inmunoterapia Sublingual/efectos adversos , Inmunoterapia Sublingual/métodosRESUMEN
OBJECTIVES: Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). METHODS: A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. RESULTS: There is a statistically significant increase of 0.369 kg/m2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m2 in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m2 per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05). CONCLUSIONS: The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.
Asunto(s)
Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Índice de Masa Corporal , Servicio de Urgencia en Hospital/estadística & datos numéricos , Administración por Inhalación , Adolescente , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Factores de Edad , Antiasmáticos/administración & dosificación , Antiasmáticos/efectos adversos , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , Pesos y Medidas Corporales , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
BACKGROUND: Eight to ten percent of patients believe that they are allergic to penicillin, yet only 10% of those patients have evidence of an immunoglobulin E (IgE) mediated allergy upon penicillin skin testing (PST). In the adult population, a negative PST result is associated with a low risk of immediate reaction on oral challenge, but further studies are needed in the pediatric population. OBJECTIVE: To calculate the negative predictive value (NPV) of the current skin testing regimen of penicillin, benzylpenicilloyl-polylysine (the major determinant), and ampicillin in a pediatric outpatient population to assess the utility of adding the minor determinant mixture to the skin testing regimen. METHODS: A retrospective chart review was conducted of all pediatric patients seen in a single-center pediatric allergy/immunology outpatient clinic between January 1, 2010, and March 1, 2016, who underwent PST for presumed penicillin drug allergy. RESULTS: Only 38% of patients who underwent PST had a drug reaction history consistent with an IgE-mediated reaction. 28.8% of the patients had a positive PST result. The addition of ampicillin to the standard PST regimen of penicillin and benzylpenicilloyl-polylysine identified an additional 4.1% of patients. Two patients (3.2%) reacted on oral challenge with a minor rash. The NPV of the PST regimen was 98%. No significant predictive variables for a positive PST result were identified. CONCLUSION: Given the high NPV of the current PST regimen, we do not recommend additional testing with the minor determinant mixture. Despite this high NPV, the utility of PST in the low-risk, low-pretest probability outpatient pediatric population was limited, and select patients may be able to proceed directly to oral challenge.