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

Lin et al. have raised concerns [1] regarding methodological aspects and perceived limitations of our nationwide cohort study on (prescribed) opioid use patterns among individuals with Crohn's disease (CD) in Sweden [2]. Although their comments are thoughtful, they partly reflect a misunderstanding of our objectives.

The primary aim of our study was to describe prescribed opioid use from 2 years before and up to 5 years after a diagnosis of CD, compared with the general population. The secondary aim was to examine annual trends in prescribed opioid use among adults with a prevalent CD diagnosis and reference individuals from the general population. As emphasised in our discussion, the study was designed as a descriptive analysis; causal attribution of CD to opioid use was explicitly not an intended outcome.

Lin et al. proposed several methodological refinements. Although scientifically reasonable, these suggestions largely address questions distinct from those we set out to answer. Their critique therefore reflects alternative research goals rather than limitations of our design. We respond to their main points below.

They suggested that confounding from conditions such as spondyloarthritis, fibromyalgia or postoperative adhesion pain should have been controlled for. We agree that such adjustments would be essential in a causal analysis of CD's independent contribution to opioid use. However, our study deliberately aimed to characterise opioid use among adults with CD as they exist, including their real-world comorbidity burden. A complementary study focusing on causal inference would indeed be valuable but represents a different research question.

They further proposed using propensity score–matched comparisons to account for greater healthcare use and comorbidity among patients with CD. Such an approach could provide important insights in a study explicitly designed to isolate causal effects. However, in our study, the general population was included for context—not as a causal comparator. The descriptive design precludes adjustment strategies aimed at answering counterfactual questions.

They also noted that opioid use is heterogeneous, suggesting further stratification of clinically relevant subgroups, such as surgical patients. We agree this is an important area for future work. Indeed, we already reported variation in opioid use by trajectory groups (non-users, intermittent users and persistent users). However, more detailed subgroup analyses would be better suited for a dedicated paper to avoid diluting the current study's core findings.

In summary, Lin et al. have highlighted valuable directions for future research but have criticised our study for not pursuing questions beyond its intended scope. Our work provided a comprehensive description of opioid prescribing in CD. This is an essential foundation for subsequent studies that may employ causal methods, refined matching techniques, or in-depth subgroup analyses. We welcome such investigations and view them as important complements to our descriptive findings.

Mehdi Osooli: conceptualization, writing – original draft, writing – review and editing. Ola Olén: conceptualization, writing – review and editing, supervision.

M.O. has worked on projects at Karolinska Institutet partly financed by grants from Pfizer, Janssen, and Alfasigma. O.O. has been PI on projects at Karolinska Institutet, partly financed by investigator-initiated grants from Janssen, AbbVie, Takeda, Pfizer, Bristol-Myers Squibb, and Ferring and also reports grants from Pfizer, Galapagos/Alfasigma, AbbVie, and Janssen in the context of a national safety monitoring program. None of those studies have any relation to the present study. Karolinska Institutet has also received fees for lectures and participation on advisory boards from Janssen, Ferring, Takeda, Bristol Myer Squibb, Galapagos/Alfasigma, and Pfizer regarding topics not related to the present study.

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.70311.