(246) Provider Practices in the Management of Pulmonary Exacerbations in the Era of Highly Effective Modulator Therapy

Background: Since the approval of elexacaftor/tezacaftor/ivacaftor (ELE/TEZ/IVA) in late 2019, the frequency of pulmonary exacerbations (PEx) in people with CF (PwCF) has declined dramatically and PEx are reportedly less severe. Anecdotally, providers prescribe oral antibiotics for the treatment of PEx rather than IV antibiotics in the hospital more frequently since the approval of ELE/TEZ/IVA. Before we can evaluate clinical outcomes associated with changes in the management of PEx in patients on highly effective modulator therapy (HEMT), we must first identify how and why providers have changed their practice patterns in the era of HEMT.

Methods: We conducted semi-structured qualitative interviews amongst adult and pediatric clinicians (physicians and advanced practice providers) at accredited CF centers nationally in late 2021 to 2022 to investigate changes in the presentation and management of PEx in PwCF prescribed ELE/TEZ/IVA. Inductive coding of interview transcripts using NVivo was conducted to identify recurrent themes and sub-themes.

Results: Thus far, 10 of a planned 20 qualitative interviews have been completed. All will be completed by June 2022. Preliminary analysis identified the following notable characteristics with regards to PEx in PwCF on ELE/TEZ/IVA compared to the pre-HEMTera: (1) PEx symptoms are milder, (2) the symptom profile is different, with less respiratory symptoms and more systemic symptoms (e.g. fatigue, weight loss), and (3) PEx are frequently managed by patients in the home setting without contacting providers. Oftentimes in the HEMT era, “patients don’t really contact us, they do their [maintenance therapies] and recover on their own…we hear about it in retrospect.” Some providers highlight the difficulties associated with changes in the presentation of PEx, explaining that, at times, “I don’t know if [patients] are having a true exacerbation.” One provider described the need to identify “more sensitive measures to identify exacerbations.” Because PEx are milder in PwCF on ELE/TEZ/IVA, a majority of PEx are treated with increased maintenance therapies or oral antibiotics. Providers explain that “we are seeing a good number of patients…get away without antibiotics.” Providers emphasized that their approach to PEx in general has not changed—as in the pre-HEMT era, they treat mild PEx with oral antibiotics and severe PEx with intravenous antibiotics. A pediatric provider described that the “[approach] has not changed after Trikafta…we treat depending on severity…and the background of the patient.” An adult provider explained that when a patient calls with symptoms suggestive of a PEx, “I’m not changing how I approach it.” Providers are equally as aggressive in their choice of therapies in PwCF on ELE/TEZ/IVA as compared to those not on ELE/TEZ/IVA.

Conclusions: From the provider perspective, PEx in PwCF on ELE/TEZ/IVA are milder. Providers more frequently prescribe increased maintenance therapies and oral antibiotics for the treatment of PEx because of the decreased severity of PEx in PwCF on HEMT. Notably, the approach to PEx management is similar as to the pre-HEMT era. Further research is necessary to objectively assess provider practices in the management of PEx and if this approach to PEx management remains effective in the era of HEMT.

Acknowledgements: This work was supported by NIH grant 1F32HL159912-01 and CFF award TOPORE21B0.

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