Estudio comparativo de pacientes con asma grave bajo tratamiento con tezepelumab, con perfil T2 alto o bajo. Estudio de resultados en salud de terapias dispensadas en la Unidad de Atención Farmacéutica a Pacientes Externos (UFPE)

Abstract

Introducción: Tezepelumab se ha mostrado efectivo en el tratamiento del asma grave no controlado (AGNC) pero aún existe escasa evidencia en vida real. Material y métodos: Se incluyeron pacientes con AGNC que cumplieron al menos 6 meses de terapia con Tezepelumab. Se analizó función pulmonar, eosinofilia, IgE, comorbilidad y cambios en control del asma (cuestionarios ACT, ACQ), escala analógica visual (VAS), calidad de vida (AQLQ), ciclos, disminución, retirada de esteroides (EO) y de otra medicación, exacerbaciones graves (ingresos + urgencias) respecto al año anterior. Se empleó la escala FEOS y EXACTO para evaluar respuesta. Los pacientes fueron divididos pacientes con fenotipo T2 bajo y pacientes con fenotipo T2 alto (eosinofílico/alérgico). Se realizaron comparaciones para el conjunto de pacientes, para cada grupo y entre ambos en T0 y T6. Resultados: Se analizaron 33 pacientes, edad 58±12 años, índice de masa corporal (IMC), 29±7 kg/ m², 31 mujeres y 2 hombres, IgE total de 107±184, eosinófilos 356±203, FENO 28±24 ppb, ACT 18±14, ACQ 4,2±3,5, con una media de ingresos hospitalarios en el año previo de 1,4±2, días de ingreso hospitalario 8±13, visitas a urgencias de 4,5±2,6, exacerbaciones globales 6,4±4, ciclos EO 4,5±3, FVC% 86±25, FEV1% 65±24, cociente FEV1/FVC 64±16. La media de tratamiento con tezepelumab fue de 6±2 meses. Fueron T2 alto 20 pacientes (61%) y 13 (39%) T2 bajo. Procedían de tratamiento biológico previo 15 pacientes (45,5%) 8 (53%) procedentes de omalizumab, 2 (13%) de mepolizumab, 4 (27%) de benralizumab y 1 (7%) de dupilumab. Presentaban comorbilidad global 28 pacientes (88%), con una o más: rinosinusitis con o sin poliposis nasal 79%, obesidad 41%, tabaquismo 37%, dermatitis atópica 30%, poliposis 22%, EREA 18%, AOS 15%, EPOC 15%, bronquiectasias 7%. Como medicación recibían habitualmente uno o más fármacos de los siguientes: dosis altas de GCI el 100% de pacientes, LABA 100%, SABA 97%, LAMA 79%, antileucotrienos 76%, xantinas 12%, antihistamínicos 39%, esteroides orales de mantenimiento en 30%. Habían ingresado en el último año 49%, 97% había acudido a urgencias, 100% recibieron ciclos de esteroides orales. Comparando basal y tras tratamiento para todo el grupo, se observaron diferencias en VAS (8 ± 0,8 vs2,4 ± 1,1, p<0.001), ACT (14,3 ± 2,3 vs 22,5 ± 1,7p<0.001) y ACQ (3,5 ± 0,5vs0,8 ± 0,6, p<0.001), AQLQ (2,3 ± 0,3 vs 5,1 ± 0,6, p<0.001), eosinófilos (356 ± 203 vs 143 ± 102, p<0.001), sin diferencias en el FEV1% (65,3 ± 23,9 vs71,4 ± 29,1, p=ns). Se redujeron las exacerbaciones graves (6,7 ± 4,2vs 0,3 ± 0,6, p<0.001), visitas a urgencias (4,5 ± 2,6 vs 0,1 ± 0,4, p<0.001), ingresos (1,4 ± 2 vs 0,1 ± 0,2, p<0.001) y ciclos de EO (4,5 ± 2,9 vs 0,1 ± 0,3, p<0.001). De los 10 pacientes con EO se retiraron en 7 y redujeron en 3. La medicación de mantenimiento y rescate se redujo significativamente (p<0.001). Al comparar en T0 ambos grupos, el ACT fue menor en el grupo T2 (p < 0.05), siendo mayor la FVC (ml) (p<0.01), FEV1 (ml) (p<0.05) y FEV1 % (p<0.05), eosinófilos (p<0.001) y FeNO (p<0.01), sin diferencias en el resto de variables clínicas. En T6 se mantuvieron estas diferencias, con FEOS inferior en no T2 (77,3 ± 9,4 vs 83,7 ± 10,4, p=0.07) sin diferencias en eosinófilos ni en el resto de variables, incluyendo la diferencia de FEV1 en ml (27 ± 157 vs 87 ± 172). Al aplicar la escala EXACTO y comparar ambos grupos, el grupo no T2 presentó menor respuesta completa (17%) frente a la del grupo T2 (52%) aunque con mayor respuesta buena (83%) frente a T2 (48%). Al comparar ambos grupos, esta diferencia fue significativa (p= 0.04). Conclusiones: Tezepelumab mejoró el control del asma en pacientes con AGNC con fenotipo T2 y noT2, disminuyendo la necesidad de esteroides orales, medicación de mantenimiento y rescate, visitas a urgencias e ingresos hospitalarios, alcanzando criterios de remisión clínica el 40%, siendo superior en fenotipo T2

Introduction: Tezepelumab has been shown to be effective in the treatment of severe uncontrolled asthma (SUCA), but there is still little real-world evidence. Materials and methods: Patients with SUCA who completed at least 6 months of therapy with Tezepelumab were included. Lung function, eosinophilia, IgE, comorbidity, and changes in ACT, ACQ, visual analog scale (VAS), AQLQ, cycles, reduction, withdrawal of steroids (EO), and other medications, and severe exacerbations (hospitalizations + emergencies) were analyzed compared to the previous year. The FEOS and EXACTO scales were used to evaluate response. Patients were divided into those with a low T2 phenotype and those with a high T2 phenotype (eosinophilic/ allergic). Comparisons were made for the patient group as a whole, for each group, and between the two groups at T0 and T6. Results: Thirty-three patients were analyzed, aged 58±12 years, body mass index (BMI) 29±7 kg/ m², 31 women and 2 men, total IgE 107±184, eosinophils 356±203, FENO 28±24 ppb, ACT 18±14, ACQ 4.2±3.5, with a mean number of hospital admissions in the previous year of 1.4±2, days of hospital admission 8±13, emergency room visits 4.5±2.6, global exacerbations 6.4±4, EO cycles 4.5±3, FVC% 86±25, FEV1% 65±24, FEV1/FVC ratio 64±16. The mean duration of treatment with tezepelumab was 6±2 months. Twenty patients (61%) were high T2 and 13 (39%) were low T2. Fifteen patients (45.5%) had previously received biological treatment: 8 (53%) had received omalizumab, 2 (13%) had received mepolizumab, 4 (27%) had received benralizumab, and 1 (7%) had received dupilumab. Twenty-eight patients (88%) had overall comorbidity, with one or more of the following: rhinosinusitis with or without nasal polyposis 79%, obesity 41%, smoking 37%, atopic dermatitis 30%, polyposis 22%, EREA 18%, OSA 15%, COPD 15%, bronchiectasis 7%. They usually received one or more of the following medications: high doses of ICS in 100% of patients, LABA in 100%, SABA in 97%, LAMA in 79%, antileukotrienes in 76%, xanthines in 12%, antihistamines in 39%, and maintenance oral steroids in 30%. Forty-nine percent had been admitted to hospital in the last year, 97% had attended the emergency department, and 100% had received courses of oral steroids. Comparing baseline and post-treatment for the entire group, differences were observed in VAS (8 ± 0.8 vs. 2.4 ± 1.1, p<0.001), ACT (14.3 ± 2.3 vs. 22.5 ± 1.7, p<0.001), ACQ (3.5 ± 0.5 vs. 0.8 ± 0.6, p<0.001), AQLQ (2.3 ± 0.3 vs. 5.1 ± 0.6, p<0.001), eosinophils (356 ± 203 vs. 143 ± 102, p<0.001), with no differences in FEV1% (65.3 ± 23.9 vs. 71.4 ± 29.1, p=ns). Severe exacerbations were reduced (6.7 ± 4.2 vs. 0.3 ± 0.6, p<0.001), as were emergency room visits (4.5 ± 2.6 vs. 0.1 ± 0.4, p<0.001), hospital admissions (1.4 ± 2 vs. 0.1 ± 0.2, p<0.001) and EO cycles (4.5 ± 2.9 vs. 0.1 ± 0.3, p<0.001). Of the 10 patients with EO, it was withdrawn in 7 and reduced in 3. Maintenance and rescue medication was significantly reduced (p<0.001). When comparing both groups at T0, ACT was lower in the T2 group (p < 0.05), with higher FVC (ml) (p<0.01), FEV1 (ml) (p<0.05), and FEV1 % (p<0.05), eosinophils (p<0.001), and FeNO (p<0.01), with no differences in the other clinical variables. At T6, these differences were maintained, with lower FEOS in non-T2 (77.3 ± 9.4 vs. 83.7 ± 10.4, p=0.07) and no differences in eosinophils or the rest of the variables, including the difference in FEV1 in ml (27 ± 157 vs. 87 ± 172). When applying the EXACTO scale and comparing both groups, the non-T2 group had a lower complete response (17%) compared to the T2 group (52%), although with a higher good response (83%) compared to T2 (48%). When comparing both groups, this difference was significant (p=0.04). Conclusions: Tezepelumab improved asthma control in patients with uncontrolled asthma with T2 and non-T2 phenotypes, reducing the need for oral steroids, maintenance and rescue medication, emergency room visits, and hospital admissions, with 40% achieving clinical remission criteria, which was higher in the T2 phenotype.