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Antagonista del receptor P2X3 (AF-219) en la tos crónica refractaria: un estudio de fase 2 aleatorizado, doble ciego

Rayid Abdulqawi¹, Rachel Dockry¹, Kimberley Holt¹

¹Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; University Hospital of South Manchester, Education and Research Centre, University Hospital of South Manchester, Manchester, UK.

Lancet (London, England)

|December 4, 2014

Resumen

AF-219, un antagonista oral de P2X3, redujo significativamente la frecuencia de la tos en pacientes con tos crónica refractaria. Este estudio destaca los antagonistas de los receptores P2X3 como un nuevo tratamiento prometedor para la tos crónica.

Área de la Ciencia:

La neurociencia es la neurociencia.
Farmacología Farmacología.

Sus antecedentes:

Los receptores P2X3 en los nervios aferentes vagales de las vías respiratorias están implicados en la hipersensibilización de las neuronas sensoriales.
Estos receptores pueden mediar la sensibilización del reflejo de la tos, contribuyendo a la tos crónica.
La tos crónica refractaria presenta una importante necesidad médica no satisfecha.

Objetivo del estudio:

Evaluar la eficacia de AF-219, un nuevo antagonista oral de P2X3, en la reducción de la frecuencia de la tos.
Investigar el papel de los receptores P2X3 en la fisiopatología de la tos crónica refractaria.

Principales métodos:

Se realizó un estudio doble ciego, controlado con placebo, de dos períodos y cruzado.
Los pacientes con tos crónica refractaria recibieron AF-219 (600 mg dos veces al día) o placebo durante 2 semanas, seguido de un lavado de 2 semanas y luego el tratamiento alternativo.
La frecuencia de la tos durante el día se evaluó utilizando grabaciones de tos ambulatoriales de 24 horas.

Principales resultados:

El tratamiento con AF-219 dio como resultado una reducción del 75% en la frecuencia de la tos en comparación con el placebo (p = 0,0003).
La frecuencia media de la tos diurna disminuyó de 37 tos/h a 11 tos/h con AF-219.
Los trastornos del gusto fueron reportados por todos los pacientes que recibieron AF-219, lo que llevó a seis retiros.

Conclusiones:

El antagonismo del receptor P2X3 reduce efectivamente la frecuencia de la tos en pacientes con tos crónica refractaria.
AF-219 demuestra potencial como una nueva clase de agentes antitusivos.
Dirigirse a los receptores P2X3 ofrece una estrategia terapéutica prometedora para la hipersensibilidad a la tos.

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