Cystic fibrosis (CF) is a rare genetic multisystemic disease, the manifestations of which are due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein and can lead to respiratory insufficiency and premature death. CFTR modulators, which were developed in the past decade, partially restore CFTR protein function. Their clinical efficacy has been demonstrated in phase 3 clinical trials, particularly in terms of lung function and pulmonary exacerbations, nutritional status, and quality of life in people with gating mutations (ivacaftor), homozygous for the F508del mutation (lumacaftor/ivacaftor and tezacaftor/ivacaftor), and in those with at least one F508del mutation (elexacaftor/tezacaftor/ivacaftor). However, many questions remain regarding their long-term safety and effectiveness, particularly in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. The impact of CFTR modulators on other important outcomes such as concurrent treatments, lung transplantation, chest imaging, or pregnancies also warrants further investigation. The French CF Reference Network includes 47 CF centers that contribute patient data to the comprehensive French CF Registry and have conducted nationwide real-world studies on CFTR modulators. This review seeks to summarize the results of these real-world studies and examine their findings against those of randomized control trials.

Rationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25–35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396–728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1–15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.

Background/Objectives: Outpatient parenteral antimicrobial therapy (OPAT) has been implemented throughout the world for the treatment of most infections. Published studies have focused on OPAT delivery, with limited data on coordination and monitoring practices. Methods: A mixed methods study, using an exploratory sequential design, was conducted at a tertiary hospital in Paris, France. Ten semi-structured interviews were conducted with prescribing physicians and professionals involved in OPAT coordination and monitoring. A general inductive approach was used to analyze verbatim data and build a framework for OPAT model characterization. Cost estimates, using a standardized scenario, were applied to each model. Results: Five OPAT coordination and monitoring models were identified. All OPATs were administered by visiting nurses in the patient’s home. Referral to an infectious disease physician was not systematic, and three models, with 3 to 50 OPAT episodes/year each, outsourced hospital-to-home coordination and monitoring to external medical service and device providers. Only one OPAT model, with 450 OPATs annually, included a nurse specialist within the unit to coordinate and monitor treatment. Clinically and/or socially vulnerable patients received OPAT through hospital at home services, which reported 30 OPATs/year. Under the standardized clinical scenario applied to each OPAT model, weekly costs ranged from EUR 1445 to EUR 2308. Conclusions: The diversity of OPAT coordination and monitoring practices identified within a single hospital suggests that similar trends may be observed in other settings, in France and elsewhere. Identifying the most cost-effective OPAT service model could guide stakeholders and facilitate the implementation of best practice recommendations in line with antimicrobial stewardship principles.