Successful Desensitisation With Cystic Fibrosis Transmembrane Conductance Regulator Modulatory Drugs in Delayed Cutaneous Hypersensitivity Reactions.

Abstract

Aim: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (MT) are recognised as novel and breakthrough treatments for people with cystic fibrosis (PwCF). Use of CFTR modulators has been shown to improve lung function and reduce pulmonary exacerbations in PwCF. However, in clinical studies, 4%-12% of PwCF developed a rash following initiation of MT. This case series aimed to improve the management of delayed hypersensitivity reactions (DHR) to MT in PwCF with the largest paediatric case series of desensitisation achieved to date and a literature review.

Methods: We successfully administered the slow desensitisation protocol in five paediatric PwCF referred to our clinic who had to discontinue MT due to delayed non-severe skin reactions. The desensitisation protocol scheduled weekly dose escalations according to the pharmacokinetics of the drugs.

Results: Four of the five patients underwent a combination of elexacaftor-tezacaftor-ivacaftor desensitisation, and one patient desensitised with ivacaftor alone. Desensitisation was achieved in all patients, but two patients required protocol modifications. Case 1 started with 0.25 tablets of elexacaftor-tezacaftor-ivacaftor based on the protocol, but the initial desensitisation dose had to be reduced to 0.125 tablets due to the development of a macular rash. In Case 5, a 0.125 tablet dose of ivacaftor was administered due to the severity of the index clinical presentation. In the other cases, the desensitisation was initiated with 0.25 tablets.

Conclusions: Desensitisation is an effective treatment approach for non-severe DHR to MT. Our case series enhances the management of DHR to MT, which is essential for PwCF.