Impact of timing of PERT on gastrointestinal symptoms in Danish children and adolescents with CF

Raun, Anne Mette Terp; Brekke, Ghita; Mølgaard, Christian; Jaudszus, Anke; Mainz, Jochen G.; Pressler, Tacjana; Skov, Marianne

doi:10.1111/apa.16143

Cited by 9 publications

(7 citation statements)

References 28 publications

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“…The CFAbd-Score has been translated into nine languages including Italian, Spanish, Portuguese, French, Dutch, Flemish and Danish, and therefore, it has been included in an international European multicentre trial (MyCyFapp) in order to assess abdominal symptoms during a project for optimization of PERT supplementation (Boon et al, 2020). Also a Danish group from the Copenhagen CF Centre assessed optimal timing of PERT, with inclusion of the CFAbd-Score (Raun et al, 2022). Besides these international projects, our PROM is presently implemented in a series of academic and industry studies.…”

Section: Validation Of Thementioning

confidence: 99%

“…Elaborated in four published steps, the first version of this CF-specific questionnaire (initially named JenAbd-Score, and from then CFAbd-Score) aimed to assess and quantify abdominal involvement in pwCF, and its development included patients, proxies and health care specialists, as recommended by FDA guidelines (Tabori et al, 2017a;Tabori et al, 2017b;Jaudszus et al, 2019). At present, the CFAbd-Score is available in nine languages and implemented in many international studies (Boon et al, 2020;Jaudszus et al, 2021;Ng et al, 2021;Raun et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 8771182019;Boon et al, 2020;Jaudszus et al, 2021;Ng et al, 2021;Raun et al, 2022).…”

mentioning

confidence: 99%

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Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

et al. 2022

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Background: The novel and highly effective CFTR modulator combination of elexacaftor-tezacaftor-ivacaftor (ETI) has been shown to improve lung function and body weight in people with Cystic Fibrosis (pwCF) carrying a F508del mutation. However, the impact of these modulators on gastrointestinal (GI) symptoms is relatively unknown. Therefore, the CFAbd-Score was developed and validated following FDA recommendations for development of a PROM including focus groups, multidisciplinary CF specialists, people with CF and their families. The aim of this study was to assess effects of ETI on GI symptoms using the CFAbd-Score.Methods: Gastrointestinal symptoms were prospectively assessed in pwCF using the CFAbd-Score before and up to 26 weeks during therapy. The CFAbd-Score was also administered to a healthy control (HC) group. The one-sided questionnaire includes 28 items grouped in five domains. Data analysis included calculation of scores with a weighting tool, developed according to FDA recommendations.Results: A total of 107 pwCF attended in four CF centres in Germany and four centres in the UK completed the CFAbd-Score on at least two occasions. Results were compared to those obtained from the questionnaire of 45 HCs. Despite differences in demographics, age and proportion of pancreatic insufficiency between German and UK patients, analyses based on linear mixed-effects models at week 24 of ETI therapy revealed that estimated marginal means (EMMs) of total CFAbd-Scores significantly reduced (mean ± SE: 14.9 ± 1.2→10.6 ± 1.4; p < 0.01). Also EMMs of all five domains significantly declined (“pain” 16.3 ± 1.6→10.2 ± 2.3, “GERD” 15.8 ± 1.8→8.2 ± 1.9, “disorders of bowel movement” 20.9 ± 1.5→16.0 ± 1.7, “disorders of appetite” 7.9 ± 1.1→2.6 ± 1.1 and “quality of life impairment” 10.1 ± 1.92→3.9 ± 1.9). However, during 24 weeks, CF participants’ symptoms mostly still did not reach the reference levels of HCs.Discussion: Using the CFAbd-Score, the first PROM specifically developed for assessment of CF-related abdominal symptoms, we demonstrate comprehensive improvements in GI symptoms after initiation of the highly effective modulator therapy ETI.

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Section: Validation Of Thementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

et al. 2022

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“…Initially, the PROM had been named JenAbd-Score (Tabori et al, 2017a), and after condensing it from a 5-sided questionnaire to a one-sided PROM, which comprises 28 symptoms grouped in five domains, it was renamed "CFAbd-Score" (Tabori et al, 2017b;Jaudszus et al, 2019;Mainz et al, 2023;Jaudszus et al, 2022;Mainz et al, 2022;Caley et al, 2023b). Presently, it is available in eleven languages and implemented in more than 25 studies around the world (Boon et al, 2020;Mainz et al, 2023;Ng et al, 2021;Mainz et al, 2022;Raun et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of abdominal symptoms during the start of a new therapy with elexacaftor/tezacaftor/ivacaftor using the novel CFAbd-day2day questionnaire

Mainz,

Barucha,

Huang

et al. 2023

Front. Pharmacol.

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Background: Elexacaftor–tezacaftor–ivacaftor (ETI) is a novel, highly effective CFTR modulator combination proven to enhance lung function and body weight in people with cystic fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions in abdominal symptoms (AS) in German, British, and Irish pwCF after 24–26 weeks of ETI using the CFAbd-Score, the first patient-reported outcome measure (PROM) specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment. To capture these immediate effects, we developed the CFAbd-day2day, a CF-specific GI-diary, following FDA and COSMIN guidelines.Aim: To prospectively capture the immediate dynamics of AS using the CFAbd-day2day 14 days before and 14–28 days after ETI initiation. In addition, we aim to provide validation steps of the novel PROM concerning sensitivity to changes.Methods: To develop the CFAbd-day2day, focus groups (community voice = pwCF and their proxies and CF specialists from different fields) were repeatedly consulted. Before and during the new ETI therapy, pwCF prospectively scored AS on a daily basis with the CFAbd-day2day.Results: Altogether, 45 pwCF attended in five CF centers prospectively completed the CFAbd-day2day before (mean ± sd:14 ± 7 days) and after (mean ± sd: 28 ± 23 days) ETI initiation. On the one hand, cumulative scores significantly decreased during the 3–4-week time frame after ETI initiation, compared to 2 weeks prior to therapy. On the other hand, many patients who revealed a relatively stable level of AS before ETI reported changes during the first days of treatment with the highly effective CFTR modulators. Factors like pain and flatulence increased in up to 21% of patients during the first 14 days of therapy, but they improved during days 15–27.Conclusion: The CFAbd-day2day, specifically developed and in the process of validation to prospectively capture GI symptoms in pwCF, provides new substantial insights into the dynamics of AS in pwCF receiving a new treatment with ETI. This novel tool is also helpful in prospectively monitoring patients with specific GI problems. International implementation and further validation steps of the diary are ongoing.

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“…We recently studied the PERT intake in our paediatric CF population and found that GI symptoms were common and did not improve by changing the timing of the PERT intake from before to after meals [ 17 ]. In the present study, we aimed to describe use of PERT and GI symptoms among adults with CF and to assess the associations between PERT dose and the demographic and clinical characteristics of pwCF.…”

Section: Introductionmentioning

confidence: 99%

Correlates of Pancreatic Enzyme Replacement Therapy Intake in Adults with Cystic Fibrosis: Results of a Cross-Sectional Study

et al. 2022

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Most people with cystic fibrosis (pwCF) develop pancreatic insufficiency and are treated with pancreatic enzyme replacement therapy (PERT). We aimed to describe the use of PERT and assess the correlates of PERT dose in adult pwCF. In a cross-sectional study at the Copenhagen CF Centre, the participants reported PERT intake, gastrointestinal (GI) symptoms and the use of concomitant treatments. Demographic and clinical characteristics were extracted from the Danish CF Registry. We used linear regression to assess the correlates of PERT dose per kg bodyweight (U-lipase/kg). We included 120 pwCF with a median age of 32.9 years, 46% women and 72% F508delta homozygote. The PERT dose ranged from 0 to 6160 U-lipase/kg per main meal (mean 1828; SD 1115). The PERT dose was associated with participants’ sex (men vs. women: 661; 95% CI: 302; 1020 U-lipase/kg), age (−16; 95% CI: −31; −1 U-lipase/kg per year) and weight (−45; 95% CI: −58; −31 U-lipase/kg per kg). Having less frequent constipation and being lung transplanted were also associated with a higher PERT dose. A third of participants did not take PERT for snacks, and this was associated with the frequency of diarrhoea. These findings indicate that PERT intake may be improved to reduce GI symptoms.

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Impact of timing of PERT on gastrointestinal symptoms in Danish children and adolescents with CF

Cited by 9 publications

References 28 publications

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

Elexacaftor-Tezacaftor-Ivacaftor Treatment Reduces Abdominal Symptoms in Cystic Fibrosis-Early results Obtained With the CF-Specific CFAbd-Score

Dynamics of abdominal symptoms during the start of a new therapy with elexacaftor/tezacaftor/ivacaftor using the novel CFAbd-day2day questionnaire

Correlates of Pancreatic Enzyme Replacement Therapy Intake in Adults with Cystic Fibrosis: Results of a Cross-Sectional Study

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