(192) Gastrointestinal symptoms in a CFTR modulator era – an international survey

Background: “How can we relieve gastrointestinal (GI) symptoms in people with cystic fibrosis (CF)?” was identified as a research priority. This was explored through an international qualitative survey amongst the CF community in 2018[1]. Following the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) in 2019, there is now a far greater proportion of people with CF (pwCF) able to access cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapy. Whilst the respiratory benefits of ETI are well documented, the effects on the GI tract are not well understood. The aim of this study was to characterise GI symptoms in the CF population and to ascertain whether these were affected by the introduction of modulators.

Methods: Electronic surveys were completed over a 1-month period by pwCF, family and health professionals (HCPs). The questionnaire was promoted through online forums such as Twitter using the twitter handles @CFAware, @questionCF and @CARDSCFresearch, Facebook and via professional networks. Ethical approval was gained from the University of Nottingham ethics committee. This analysis presents a summary of the closed questions, with thematic analysis ongoing and performed using NVivo software.

Results: There were 164 respondents from 11 countries, with the majority of respondents (85%) from the UK. Two thirds of respondents (n=110, 67%) were from the lay community (pwCF 54%, parent 12%, other relative 1%). HCPs (n=54, 33%) were represented by 10 professional groups, with dieticians the largest professional group (44%). Most pwCF were on a CFTRm (n=89, 81%), mostly commonly ETI.

The majority of respondents from both the lay community (84/95, 88%) and HCPs (33/35, 94%) felt that GI symptoms impacted on quality of life (QoL) for pwCF. Of those not on a CFTRm, 53% (10/19) missed school or work because of their GI symptoms vs 27% (20/75) people on a CFTRm. The most common GI symptoms experienced at least once a week or more regardless of modulator status were: wind/gas and rumbling noises in the stomach as well as loose bowel motions (CFTRm group) and bloating (no modulator group). Symptoms most commonly reported as improved by pwCF since starting a modulator were: stomach pain/discomfort (n=29,38%), bloating (n=28,37%) and loose motions (n=28,37%) (scale: worse, same, better, N/A). However, stomach cramps and bloating were still identified as the symptoms most impacting QoL in both groups.

HCP reported the most common symptoms affecting QoL for pwCF were stomach pain, bloating and diarrhoea/constipation. Symptoms most commonly improved following CFTRm were: improved appetite (26/34,77%), stomach pain/ discomfort (21/34, 62%) and stools that float (18/33,55%).

Conclusions: Although CFTR modulators have improved the experience of GI symptoms for some pwCF, this survey demonstrates that GI symptom response varies and GI symptoms continue to be a problem for pwCF regardless of their modulator status and impacted on QoL. Improvements reported by the lay community were different to those of HCPs. Understanding GI symptoms remains a relevant research question and a better understanding of the physiology underlying them needs to be further explored.

Acknowledgements:

References: [1] Smith S, Rowbotham N, Davies G, et al. How can we relieve gastrointestinal symptoms in people with cystic fibrosis? An international qualitative survey. BMJ Open Respir Res. 2020. 7(1):e000614.