CFTR modulator drug desensitization: Preserving the hope of long term improvement

Abstract

The development of modulator therapy has, for the first time, allowed direct targeting of the underlying cause of cystic fibrosis (CF), the cystic fibrosis transmembrane conductance regulator (CFTR). Patients treated with CFTR modulators have improvement in lung function and decreased rates of pulmonary exacerbations. In 2019, elexacaftor/tezacaftor/ivacaftor was approved for use in the United States, opening these therapies to 90% of patients with CF. Intolerable adverse drug reactions to CFTR modulators results in discontinuation of therapy, which can be devastating to our patients. We describe our approach to two cases, not previously reported, of rash to elexacaftor/tezacaftor/ivacaftor in patients with a previous history of cutaneous adverse reactions to dual modulator therapy that had been addressed by desensitization. Case 1 was able to tolerate elexacaftor/tezacaftor/ivacaftor after desensitization to the triple combination therapy, while in Case 2 tolerance was obtained by treating through the reaction. The loss of tolerance in these patients was unexpected, and may be a common finding in patients with history of cutaneous adverse reactions to these drugs. We hope reporting our experience, including our desensitization protocol, may benefit CF patients for whom these drug reactions may be limiting access to powerful disease altering therapies.

Keywords: CFTR modulator; cystic fibrosis; desensitization.