Long-term durability of ivacaftor (IVA) treatment benefit in people with cystic fibrosis (PwCF)

Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1s (ppFEV1) was estimated over 5years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5years. Findings were generally consistent with those of shorter follow-up periods. IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).

PRS31 Modelling Survival of People with Cystic Fibrosis (PWCF) Aged ≥12 YEARS Homozygous for the F508DEL Mutation Treated with Ivacaftor/Tezacaftor/Elexacaftor and Ivacaftor (IVA/TEZ/ELX)

Relationship between skeletal muscle indicators and clinical outcomes in cystic fibrosis is modified by adiposity and CFTR modulator use: a cross-sectional analysis.

Background:Cystic fibrosis (CF) outcomes are influenced by a myriad of genetic, microbiological, and environmental factors, as well as socioeconomic constraints. Studies have shown that low socioeconomic status is associated with a higher risk of death, lower body weight and height, worsened pulmonary function, and increased pulmonary exacerbation in children with CF. Screening for social risk factors (SRFs) is one possible approach to help mitigate unmet social needs in people with CF (PwCF).Objectives:Does a positive screening response for SRF correlate with health outcomes in PwCF?Design:This is a single-center, retrospective analysis of outcomes in adult PwCF. The study includes data from 2021 to 2022.Methods:A social needs screening tool was administered to identify SRF in PwCF in eight domains: housing, food, transportation, utilities, healthcare cost, medication cost, income/employment, and education. A total of 121 PwCF were included in the analysis. Linear mixed-effects models, Poisson regression, and mixed-effects Cox regression were used for analyses of multivariate models.Results:When adjusted for multiple covariables, PwCF who screened positive for SRF had similar lung function and BMI as PwCF who reported no SRF and an increased CF exacerbation rates per person/per year when compared to their peers, 1.700 (1.275, 2.266) versus 0.829 (0.608, 1.130) (p = 0.006). Adjusted models showed that the median time to exacerbation was significantly lower in PwCF who screened positive for SRF (210 days vs 389 days).Conclusion:PwCF who responded positively for SRF experienced an increased rate of CF exacerbation, and this finding remained significant when adjusted for multiple variables, including new CF medications. Medication cost, income/employment concerns, and food insecurity emerged as the most significant predictors of exacerbation rates and time to the next exacerbation. Further studies are needed to evaluate effective interventions and resources to mitigate SRF.

IntroductionLower socioeconomic status is associated with significantly poorer outcomes in weight, lung function, and pulmonary exacerbation rates in people with cystic fibrosis (PwCF).Global aimWe aim to reduce health disparities and inequities faced by PwCF by screening for and addressing unmet social needs.Specific aimsWe aimed to increase routine social determinants of health (SDoH) screening of eligible PwCF from 0% to 95% and follow‐up within 2 weeks for those PwCF who screened positive and requested assistance from 0% to 95% by December 31, 2021.MethodsThe Model for Improvement methodology was used. A process map and a simplified failure mode effects analysis chart were created for the screening and SDoH follow‐up process. For those who screened positive for SDoH and requested assistance, follow‐up contact was made to offer intervention.InterventionAdult PwCF who had at least one UVA Clinic encounter in 2021 were screened for SDoH. The SDoH screening tool included eight domains: housing, food, transportation, utilities, health‐care access, medication access, income/employment, and education. Follow‐up was completed with all PwCF who screened positive for SDoH.ResultsA total of 132 of 142 (93.0%) PwCF eligible for screening completed the SDoH screening. Of the PwCF who completed screening, 56 (42.4%) screened positive for SDoH. A follow‐up rate of 100% was achieved in June 2021 and maintained through December 2021.ConclusionImplementing screening for SDOH and follow‐up to mitigate social difficulties in adult PwCF at UVA was successful and could be reproduced at other CF care centers.

Rationale: Lung transplant (LTx) is a potentially lifesaving treatment option for individuals with advanced cystic fibrosis (CF), but more people with CF (PwCF) and advanced lung disease die each year than undergo transplant in the United States. Little is known about these individuals' LTx information needs and factors influencing their decision-making process related to transplant. Objectives: To examine PwCF's experiences with and preferences for provision of LTx information and to identify transplant information needs that CF clinicians are well positioned to address. Methods: We performed semistructured qualitative interviews in two separate cohorts: PwCF without LTx and PwCF with LTx between July 2019 and June 2020. Questions focused on awareness and knowledge about LTx, perspectives related to communication about transplant in the CF clinic, and experiences with LTx. Thematic analysis was used to organize the qualitative data. Exemplar quotes were chosen to llustrate domains that emerged pertaining to the research objectives. Results: Fifty-five PwCF, including 35 without LTx and 20 with LTx, participated. One-third of PwCF without LTx had normal or near-normal lung function. Key common domains among PwCF with and without LTx were identified, including information needs, connections with LTx recipients, and conversations with CF clinicians. For PwCF with and without transplant, concrete information needs were identified: success or survival, social support, surgery, recovery/pain, and quality of life post-transplant. The importance of connecting with LTx recipients to hear their stories and experiences was emphasized by both PwCF with and without transplant. Important considerations for timing and content of discussions with CF clinicians were identified, including having information presented early (before LTx referral is needed) and in limited detail at first. PwCF without LTx wanted to understand how LTx was relevant to them, with a focus on the unique experience of CF. PwCF with LTx emphasized the need for a centralized resource for LTx information. Conclusions: The findings provide content areas for CF clinicians to focus on as they proactively initiate conversations about LTx and support the development of tools to aid in discussions about LTx for PwCF.

Physical well-being and burden of care in adults on modulator therapy: A mixed methods study of patient-reported experiences from the Well-ME survey.

Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma

Background In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data. Research design and methods The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response rate was compared using a weighted logistic regression. Time-to-event outcomes were evaluated using a Cox regression. Results For SCHOLAR-5, the sum of weights for the 143 patients was 85 after SMR weighting, versus 86 patients in ZUMA-5. The median follow-up was 29.4 months and 25.4 months for ZUMA-5 and SCHOLAR-5, respectively. The hazard ratios for overall survival and progression-free survival were 0.52 (95% confidence interval (CI): 0.28–0.95) and 0.28 (95% CI: 0.17–0.45), favoring axi-cel. Conclusion This updated analysis, using a longer minimum follow-up than a previously published analysis, shows that the improved efficacy of axi-cel, relative to available therapies, in r/r FL is durable. .

The Changing Face of Lung Transplant Waiting Lists in the Era of CFTR Modulators

BackgroundThe COVID-19 pandemic has been challenging for many but especially for people with pre-existing co-morbidities such as people with cystic fibrosis (PWCF). The aim of this study was to examine the impact of COVID-19 pandemic on hospital services access to essential medication, employment, and mental health of PWCF.MethodsA cross-sectional survey developed by University College Dublin and Cystic Fibrosis Ireland was uploaded on SmartSurvey UK and advertised by CF Ireland to CF community via CFI website and social media in October 2020. Logistic Regression was used for analysis.Results119 PWCF participated. 56 (47.5%) deferred hospital visits for CF care from 1-6 months: (57.4%) to 3 months; 42.6% 4 months-over 6 months), due to hospital closure (11.5%) & fear (69.8%). When adjusted for gender and location, PWCF aged <35 years were twice as likely to defer hospital visits as compared to those >35 years (P = 0.048). Online consultation and prescription via email was new for >50% of PWCF and >80% found it useful. Amongst those who worked (46.2%), 87.2% (n = 48) worked from home during COVID19. More PWCF <35 years (9.6%) worked onsite as compared to those >35 years (1.9%). 95% of employers were sympathetic for PWCF who cocooned while working from home (41.7%), however, overall, approximately 1/3rd of all employers were considered unsympathetic. 24.4% found access to CF medications challenging and 7 (5.9%) had to find alternative. After adjustment for gender and working, PWCF < 35 years were more likely to feel “nervous” (OR: 3.28; P = 0.017), “nothing could cheer them up” (OR: 3.24; P = 0.038) and “tired” (OR: 2.76; P = 0.016) compared to those >35 years.ConclusionsFear was a strong reason for essential hospital visit deferrals in COVID19, but hospital closures played an important part also. Prescription by email was novel and popular. There has been a serious impact on the mental health of this vulnerable group.Key messages COVID-19 impacted hospital visits due to fear and hospital closures; younger PWCF deferred more and for longer.The negative impact of COVID-19 on mental health was more pronounced in older PWCF.

Introduction and ObjectivesPeople with Cystic Fibrosis (PWCF) may be presumed to be at lower risk of periodontal disease due to long term antibiotic use but this has not been comprehensively investigated. The oral hygiene and periodontal status of PWCF in comparison to the general population is not well established.The objective of this systematic review was to critically evaluate the literature on periodontal and oral hygiene status in PWCF to see if this group are at increased risk of periodontal disease (gingivitis or periodontitis). Data Sources5 databases were searched: Scopus, MEDLINE, Embase, Cochrane Library and Web of Science. Study SelectionThe search resulted in 614 publications from databases with one more publication identified by searching bibliographies. 13 studies were included in the qualitative analysis. ConclusionsThe majority of studies showed better oral hygiene, with lower levels of gingivitis and plaque among people with Cystic Fibrosis (PWCF) than controls. Interestingly, despite this, many studies showed that PWCF had higher levels of dental calculus. Three studies found there was no difference in Oral Hygiene between PWCF and controls. One study found that PWCF aged between 6 and 9.5 years had increased levels of clinical gingivitis, and one study showed that PWCF with gingivitis had more bleeding on probing than people without CF. The vast majority of PWCF examined were children- only five studies included people over 18 years, and only one looked exclusively at adults. There is a need for further study into the periodontal health of PWCF- particularly those over the age of 18. Clinical SignificanceThere are currently no guidelines referring to oral care in PWCF. Studies have suggested that the oral cavity acts as a reservoir of bacteria which may colonise the lungs.If PWCF are at increased risk of periodontal disease, they should attend for regular screenings to facilitate early detection.

Among people with cystic fibrosis (PwCF), methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) have been increasing in prevalence and can cause rapid declines in lung function and increased mortality. Fortunately, since 2019, incidence has started to decline. The purpose of this study was to evaluate if doxycycline has comparable efficacy to vancomycin for the treatment of APEs in PwCF. Given the potential toxicities and intolerances associated with vancomycin, evaluating alternative therapies such as doxycycline is warranted. A multicenter retrospective cohort study was conducted in adult and pediatric PwCF who received greater than 48 hours of either vancomycin or doxycycline to treat MRSA-associated APEs between May 1, 2014, and August 31, 2021. The primary outcome was the number of PwCF with a return to ≥90% of baseline forced expiratory volume in the first second (FEV1). There were 229 PwCF encounters screened, of which 89 met inclusion criteria (n = 26, vancomycin; n = 63, doxycycline). There were no differences between vancomycin and doxycycline for the primary outcome: 18/26 (69.2%) in the vancomycin group vs 51/63 (81.0%) in the doxycycline group (P = 0.23). Secondary outcomes were similar between groups, including no difference in incidence of acute kidney injury (AKI), although a significantly higher incidence of adverse events occurred in the vancomycin arm. The findings of this study suggest doxycycline may be a reasonable alternative to vancomycin for MRSA-associated APEs, particularly in PwCF who may not tolerate vancomycin or who require concomitant nephrotoxins such as intravenous (IV) aminoglycosides.

Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Early glucose abnormalities revealed by continuous glucose monitoring associate with lung function decline in cystic fibrosis: A five-year prospective study