Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma.

BACKGROUND: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. OBJECTIVE: To compare global differences in ease of access to biologics. METHODS: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. RESULTS: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/µL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. CONCLUSIONS: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.

Development of a Tool to Measure the Clinical Response to Biologic Therapy in Uncontrolled Severe Asthma: The FEV1, Exacerbations, Oral Corticosteroids, Symptoms Score.

BACKGROUND: There is a lack of tools to quantify the response to monoclonal antibodies (mAbs) holistically in severe uncontrolled asthma patients. OBJECTIVE: To develop a valid score to assist specialists in this clinical context. METHODS: The score was developed in four subsequent phases: (1) elaboration of the theoretical model of the construct intended to be measured (response to mAbs); (2) definition and selection of items and measurement instruments by Delphi survey; (3) weight assignment of the selected items by multicriteria decision analysis using the Potentially All Pairwise RanKings of All Possible Alternatives methodology using the 1000minds software; and (4) face validity assessment of the obtained score. RESULTS: Four core items, with different levels of response for each, were selected: severe exacerbations, oral corticosteroid use, symptoms (evaluated by Asthma Control Test), and bronchial obstruction (assessed by FEV1 percent predicted). Severe exacerbations and oral corticosteroid maintenance dose were weighted most heavily (38% each), followed by symptoms (13%) and FEV1 (11%). Higher scores in the weighted system indicate a better response and the range of responses runs from 0 (worsening) to 100 (best possible response). Face validity was high (intraclass correlation coefficient of 0.86). CONCLUSIONS: The FEV1, exacerbations, oral corticosteroids, symptoms score allows clinicians to quantify response in severe uncontrolled asthma patients who are being treated with mAbs.

Enfermedad del pulmón del granjero: análisis de 75 casos / Farmer's lung disease: Analysis of 75 cases

Introducción: La enfermedad del pulmón de granjero (EPG) es una forma frecuente de neumonitis por hipersensibilidad, posiblemente infradiagnosticada. El objetivo de este estudio es describir las características clínicas, la evolución y los factores que influyen en el pronóstico de los pacientes con EPG. Pacientes y métodos: Estudio retrospectivo que incluyó a todos los pacientes diagnosticados de EPG por haber presentado una exposición ambiental de riesgo, una clínica, una función pulmonar y una radiología compatible, en los que se demostró sensibilización antigénica y/o una anatomía patológica concordante. Resultados: Se incluyeron 75 pacientes con EPG, 50 con forma aguda o subaguda (FAS) y 25 con forma crónica (FC). Un 44% de los pacientes (n=33) fue diagnosticado durante los meses de marzo y abril, especialmente aquellos con FAS en comparación con las FC (52 vs. 28%; p=0,0018). En las FAS la DLco presentó una mejoría durante el seguimiento (p=0,047). La determinación de anticuerpos IgG específicos fue positiva en 39 pacientes (78%) con FAS (44% de ellos frente a Aspergillus) y en 12 con FC (48%). La realización de la evitación antigénica (OR 9,26, IC 95% 1,3-66,7, p=0,026) y la administración de tratamiento inmunodepresor (OR 16,13, IC 95% 1,26-200, p=0,033) fueron los factores predictores de mejor evolución de la enfermedad. Conclusiones: La EPG presenta un inicio con predominio estacional en nuestro medio. Las FC presentan habitualmente determinación de anticuerpos IgG específicos negativos, a diferencia de las FAS, donde los anticuerpos frente Aspergillus son las más frecuentes. La evitación antigénica y el tratamiento inmunodepresor son posibles predictores de mejor evolución de la enfermedad (AU)

Introduction: Farmer's lung disease (FLD) is a common form of hypersensitivity pneumonitis possibly underdiagnosed in our midst. The aim of this study was to describe clinical characteristics, evolution and factors that influence the prognosis of patients with FLD. Patients and methods: A retrospective study that included all patients diagnosed with FLD presenting an environmental exposure risk, a clinic, lung function and a compatible radiology, in which antigen sensitisation was demonstrated and/or a concordant pathology. Results: We selected 75 patients with FLD, 50 with acute or subacute form (ASF) and 25 with chronic form (CF). Forty-four percent of patients (n=33) were diagnosed during the months of March and April, especially those with ASF compared to CF (52 vs. 28%; P=.0018). In the ASF group, DLco showed an improvement during follow-up (P=.047). The determination of specific IgG antibodies was positive in 39 patients (78%) with ASF (44% of them against Aspergillus) and CF 12 (48%). The realisation of antigenic avoidance (OR 9.26, 95% CI 1.3-66.7, P=.026) and the administration of immunosuppressive therapy (OR 16.13, 95% CI 1.26-200, P=.033) were predictors of better disease progression. Conclusions: FLD is predominantly seasonal in our environment. CF usually has a negative specific IgG antibodies unlike ASF, where antibodies against Aspergillus are the most common. The realisation of antigenic avoidance and immunosuppressive treatment are possible predictors of better disease progression (AU)