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Xu J, Zhang EM, Wang JB. Letter to the Editor: Sex-specific differences in 5-aminosalicylic acid therapy for ulcerative colitis: Is it still the case in smokers? World J Gastroenterol 2027; 33(3): 126483 [DOI: 10.3748/wjg.126483]
World J Gastroenterol. Jan 21, 2027; 33(3): 126483 Published online Jan 21, 2027. doi: 10.3748/wjg.126483
Letter to the Editor: Sex-specific differences in 5-aminosalicylic acid therapy for ulcerative colitis: Is it still the case in smokers?
Jing Xu, En-Ming Zhang, Jing-Bo Wang
Jing Xu, Department of Gastroenterology, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China
En-Ming Zhang, Department of Gastroenterology, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China
Jing-Bo Wang, Department of Oncology, The First Hospital of Qiqihar, Qiqihar 161005, Heilongjiang Province, China
Jing-Bo Wang, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Co-first authors: Jing Xu and En-Ming Zhang.
Author contributions: Xu J and Zhang EM conducted the investigation and drafted the original manuscript. Wang JB performed the conceptualization, conducted the investigation, supervised the study and revised the manuscript. Xu J and Zhang EM contributed equally to this work as co-first authors.
AI contribution statement: AI was used only for language editing.
Conflict-of-interest statement: The authors declare no conflict of interest.
Corresponding author: Jing-Bo Wang, MD, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. wangjingbo201001@163.com
Received: August 14, 2026 Revised: September 13, 2026 Accepted: November 5, 2026 Published online: January 21, 2027 Processing time: 101 Days and 3.2 Hours
Abstract
A retrospective study conducted by Liu et al published a study in World Journal of Gastroenterology, reported that pronounced sex-specific differences existed in 5-aminosalicylic acid (5-ASA) therapy efficacy and patient prognosis for Chinese ulcerative colitis (UC) patients. Male sex is associated with more frequent relapses, a lower likelihood of endoscopic mucosal healing (EMH), and a higher risk of colectomy. Nonetheless, two major methodological limitations may weaken the robustness and generalizability of its conclusions. First, marked imbalance existed in smoking status between sexes and was poorly addressed by 1:1 propensity score matching, yielding an almost smoker-free cohort and consequently introducing great selection bias. Second, the lack of explicit definition of disease duration introduced confounding bias to the prognostic assessment of sex. Disease duration was revealed to be an independent factor associated with both EMH and risk of colectomy in current study, yet the ambiguity of this factor may distort the multivariate Cox regression analysis and may further confound the prognostic value of sex. Specific validation in patients who smoke, an explicit definition of disease duration, and reanalysis of the prognostic models are highly recommended to assess the prognostic effects of sex and disease duration in UC patients treated with 5-ASA.
Core Tip: Although Liu’s study delivered clinically relevant evidence of sex-based response difference to 5-aminosalicylic acid in ulcerative colitis, two major methodological limitations may weaken its robustness and generalizability. The conclusions drawn from this study could not be directly extended to patients who smoke, and external validation in smokers is needed. The authors should also provide an explicit definition of disease duration and conduct supplementary analyses to elucidate the effect of longer disease duration on outcomes.
