Letter: Crohn's Disease or Comorbidity? Reassessing Opioid Prescribing Patterns

In their population-based matched cohort study, Osooli et al. reported that opioid use was markedly higher among patients with Crohn's disease (CD) than matched individuals from the general population, not only following but also preceding CD diagnosis [1]. Although this raises important concerns regarding pain management and prescribing practices in CD, several methodological issues and interpretative limitations warrant further examination.

First, the study did not account for comorbid chronic pain conditions frequently observed in CD. Crohn's disease has well-documented overlap with axial spondylarthritis [2], a group of inflammatory disorders independently linked to increased opioid use [3]. Without excluding this or adjusting for its presence, the study may have inadvertently attributed related prescriptions to CD. Moreover, the contribution of other painful conditions such as fibromyalgia or postoperative adhesion pain to opioid use was not described or controlled for. The observed opioid burden may thus reflect aggregate comorbidity effects rather than CD-specific pain alone.

Second, using the general population as a comparator may have introduced surveillance bias and comorbidity imbalance. Patients with CD interact more frequently with healthcare systems, increasing the likelihood that opioid prescriptions are captured, regardless of actual pain severity [4]. Moreover, comorbidities influencing both healthcare use and opioid risk—such as musculoskeletal disorders, depression, and malignancy—were not matched or adjusted for. These differences may contribute to the association, and the lack of propensity score matching limits comparability between cohorts.

Third, although the study reported inflammatory bowel disease treatment distribution, it did not explore heterogeneity within the CD cohort that may influence opioid use. Factors such as surgical history, biologic use intensity, and disease activity shape pain experience and prescribing decisions [5]. Without stratified analysis of subgroups—such as patients with refractory disease or post-surgical recovery—the observed association may obscure clinical variation and limit applicability across the broader CD population.

Finally, established risk factors for both CD severity and opioid use—such as smoking [6] and socioeconomic status [7]—were not considered. These variables correlate with pain burden and prescribing practices, and their omission raises the risk of residual confounding. Thus, the strength and specificity of the reported CD–opioid association may be overstated, especially if these unmeasured factors are unevenly distributed between cohorts.

Taken together, these limitations highlight the need for cautious interpretation of the reported association between CD and opioid use. While the study addressed a clinically relevant issue, the roles of comorbidities, healthcare utilisation, and unmeasured confounders warrant acknowledgment.

Kuan-Ju Lin: writing – original draft, project administration. Cheng-Hsien Hung: methodology, writing – review and editing, supervision, resources. James Cheng-Chung Wei: writing – review and editing, supervision.

The authors declare no conflicts of interest.

This article is linked to Osooli et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70203 and https://doi.org/10.1111/apt.70356.