Introduction

There is a need to reliably measure celiac disease (CeD) symptom severity in clinical trials. The Celiac Disease Symptom Diary 2.1^© (CDSD 2.1^©) is a daily diary that assesses five core symptoms of CeD (abdominal pain, bloating, diarrhoea, nausea and tiredness) and was developed following FDA guidelines for fit-for-purpose patient-reported outcome measures (PROMs). The objective of this study was to psychometrically validate the CDSD 2.1^©.

Aims & Methods

Psychometric properties of the CDSD 2.1^© were evaluated using data from a 12-week US observational study (NCT05309330) in patients with CeD maintaining a gluten-free diet. Participants completed the CDSD 2.1^© daily and other symptom severity PROMs at specified timepoints to evaluate validity, reliability and responsiveness. The average CDSD 2.1^© weekly severity scores did not include tiredness in order to focus on GI-related symptoms.

Results

Overall, 480 participants (338 adults, 142 adolescents) completed the study. Weekly average gastrointestinal (GI; abdominal pain, bloating, nausea, diarrhoea) CDSD 2.1^© scores demonstrated high internal consistency reliability (Cronbach’s alpha, Week 0 = 0.77). Convergent validity was confirmed by moderate-to-strong correlations between weekly average GI CDSD 2.1^© scores and Gastrointestinal Symptom Rating Scale (GSRS) domains at Week 0 and Celiac Symptom Index (CSI) scores at Week 3 (r = 0.48–0.73; p ≤0.05). Known-groups validity was supported with significant differences in weekly average GI CDSD 2.1^© scores observed by Patient Global Impression of Severity (PGIS) groups (p <0.001). Test-retest reliability of GI CDSD 2.1^© scores was demonstrated among stable patients on the PGIS (intraclass correlation coefficient = 0.89). Responsiveness was established as weekly average GI CDSD 2.1^© change scores followed the expected pattern among PGIS change groups.

Conclusion

This study demonstrates that CDSD 2.1^© is a valid, reliable and responsive PROM of CeD GI symptom severity that could be used to construct endpoints in clinical trials for CeD therapies.

Disclosure

SG, DAL, LMM, MJT, MA and RS are employees and shareholders of Takeda. NJR and LMc are employees of RTI Health Solutions, which receives funding from pharmaceutical companies for patient-reported outcome consulting services. They receive no compensation from the pharmaceutical companies and their RTI salary is not related to the projects on which they work. DA has served as a consultant for Takeda Pharmaceuticals and Ironwood Pharmaceuticals. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda. EL serves as a consultant for Takeda Pharmaceuticals and is an author for UpToDate (celiac section) for which he receives royalties.

Introduction

The advent of direct-acting antivirals (DAAs) is a major breakthrough in hepatology representing the therapeutical standard of care in patients with chronic hepatitis C virus infection. Despite high rates of sustained virological response (SVR), DAAs therapy doesn’t eliminate the risk of thrombotic events.

Aims & Methods

We aimed to assess the prevalence of nontumoral portal vein thrombosis (PVT) after SVR.We prospectively analyzed a cohort of patients with HCV-related liver cirrhosis treated with paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD) ± ribavirin and ledipasvir/sofosbuvir (LED/SOF) ± ribavirin for 12/24 weeks, in a gastroenterology center from Romania, between January 1^st 2016 and July 1^st 2021. All patients with presumption of thrombosis were evaluated by vascular Doppler, abdominal ultrasound and confirmed by CT scan.

Results

The study included 730 patients treated with DAAs, of which 35 were diagnosed with non-malignant PVT after-SVR (15 men and 20 women, mean age 57.86 ± 7,068 years), corresponding to a prevalence of 4.8%. The mean time from SVR to complication was 290.00 ± 116.639 days. Most patients with nontumoral PVT received LED/SOF (71.4%), while the rest received PrOD (28.6%). During the study, an improvement in the Child-Pugh and MELD score was observed at the SVR. The evolution changes slightly at the 48-week assessment, with a slight increase in the proportion of patients in the Child B class and MELD ≥ 15. The pro- and anticoagulant factors evaluated reflect the classic hemostatic profile of patients with liver cirrhosis and PVT, characterized by increased FII, FVIII and FvW and decreased anticoagulant factors (PC, PS, ATIII).

Conclusion

The study included 730 patients treated with DAAs, of which 35 were diagnosed with non-malignant PVT after-SVR (15 men and 20 women, mean age 57.86 ± 7,068 years), corresponding to a prevalence of 4.8%. The mean time from SVR to complication was 290.00 ± 116.639 days. Most patients with nontumoral PVT received LED/SOF (71.4%), while the rest received PrOD (28.6%). During the study, an improvement in the Child-Pugh and MELD score was observed at the SVR. The evolution changes slightly at the 48-week assessment, with a slight increase in the proportion of patients in the Child B class and MELD ≥ 15. The pro- and anticoagulant factors evaluated reflect the classic hemostatic profile of patients with liver cirrhosis and PVT, characterized by increased FII, FVIII and FvW and decreased anticoagulant factors (PC, PS, ATIII).