Comment on Ejaz et al. Letter to the Editor

We appreciate the thoughtful commentary from Ejaz et al. [1] on our article, “Assessment of PBC Pruritus from the ITCH-E Study: Quality of Life, Productivity, and Treatment Experiences.” [2] In the following sections, we address each point raised, providing clarifications and context supported by our published data. Ejaz et al. raise the concern that recruiting via an advocacy group and physician panels might overrepresent patients with more pronounced symptoms, potentially inflating the overall symptom severity in our cohort. Indeed, 62 of our 90 participants came from the PBCers Organisation and 28 from physician panels. Our study's intent was not to estimate the population prevalence of pruritus severity, but rather to compare patient-reported outcomes between pruritus severity groups. We intentionally included both no/mild pruritus (NMP, n = 40) and moderate/severe (MSP, n = 50) pruritus cases. We cautioned in our article that our sample may not reflect all PBC patients due to the sample size. We fully agree with Ejaz et al. that future studies using broader recruitment strategies would be valuable. A higher proportion of MSP patients received OCA (30% vs. 18% in NMP). OCA can worsen pruritus in PBC, and we considered this in our analysis. We included OCA status as a covariate, and key differences between MSP and NMP (itch severity, fatigue, quality of life [QoL]) remained significant after adjustment, suggesting symptom burden is not fully explained by OCA. Ejaz et al. suggest a stratified analysis by OCA exposure to separate disease-related vs. treatment-induced pruritus. Subgroup analysis was not possible due to small numbers (22 patients on OCA). Ejaz et al. note our WPAI analysis focused on employed individuals. While absenteeism and presenteeism apply only to employed participants, WPAI also measures “activity impairment” for all, which includes housework and childcare. There was a significantly higher activity burden in MSP: 57% vs. 36% (p < 0.001), indicating pruritus affects daily functioning beyond paid work. Additionally, employment was lower in MSP (42% vs. 53%), suggesting pruritus may reduce workforce participation. We agree the broader “hidden” burden including unpaid work, social roles, and caregiving needs study and calls for research on indirect and societal costs. In conclusion, we appreciate Ejaz et al.'s comments and agree these warrant further study to enhance our understanding of the impact of cholestatic pruritus on QoL in PBC and support patient-centered care. C.L. has received research grants from Calliditas Therapeutics, CymaBay Therapeutics, Escient Pharmaceuticals, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Kowa, Mirum Pharmaceuticals, Target RWE, and Zydus. M.J.M. has received research grants or contracts from CymaBay Therapeutics, Genfit, Gilead Sciences, GSK, Ipsen, and Mirum Pharmaceuticals; consulting fees from CymaBay Therapeutics, GSK, Intra-Sana, Ipsen, Ironwood Pharmaceuticals, Mallinckrodt, and Mirum Pharmaceuticals; and support for attending meetings and/or travel from CymaBay Therapeutics, GSK, Ipsen, and Mallinckrodt. C.F.M.P. is an employee of Gilead Sciences and, in the course of employment, has received stock options and other stock awards for ordinary shares of Gilead Sciences. Assessment of PBC Pruritus From the ITCH-E Study: Quality of Life, Productivity, and Treatment Experiences. https://doi.org/10.1111/liv.70374. Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.