Pruritus is a debilitating symptom for patients with
Alagille syndrome (ALGS). In a previously reported trial of
maralixibat, an investigational
antipruritic agent,
itching was assessed using a digital diary based on twice-daily caregiver observation of
itching severity (Itch Reported Outcome, ItchRO[Observer]). The goal of this study was to characterize
pruritus in participants with ALGS at baseline in this trial, as assessed by the ItchRO instrument and the physician-observed clinician scratch scale (CSS), relative to
biomarkers putatively associated with
pruritus and health-related quality of life assessment. Thirty-seven participants with ALGS (median age of 6 years; range 1-17 years) were enrolled. No association was identified between CSS and ItchRO(Obs) (r = 0.22, P = 0.2). Neither CSS nor ItchRO were associated with serum
bile acids (r = -0.08, P = 0.6 for both) or autotaxin (r = 0.22, P = 0.2; r = 0.28, P = 0.12). There was no significant association between Pediatric Quality of Life Inventory total parent scores and CSS or ItchRO (r = -0.23, P = 0.2; r = -0.16, P = 0.36). There was a significant association between ItchRO and Multidimensional
Fatigue Scale and Family Impact Module total scores (Pearson correlation coefficient -0.575, P = 0.0005; 0.504, P = 0.002). In exploratory analysis, selected questions relating to
fatigue and sleep disturbance (n = 12) from Pediatric Quality of Life Inventory, Multidimensional
Fatigue Scale, and Family Impact Module were correlated with
pruritus scores; positive associations were identified. Conclusion:
Itching scores did not correlate with each other, nor with putative serum
biomarkers of
pruritus, and further, did not correlate with quality of life. Hypothesis-generating analyses implicate sleep disturbance and
fatigue as key associations with caregiver observations of
itching. This is highly relevant to the selection of
surrogate endpoints for clinical trials of
pruritus therapies.