Letter: Are Antispasmodics Truly Ineffective in IBD? Considerations on Nuanced Interpretation and Stratified Analysis. Authors' Reply

We appreciate the opportunity to respond to the comments submitted by Mao et al. [1] relating to our article [2]. They provided thoughtful commentary about the strengths and weaknesses of our study, and we agree with several concerns and recommendations that they shared. For example, they highlighted the potential limitations of relying upon ICD-10 codes to assess the abdominal pain status of each patient, including the lack of ‘granularity’ in data related to pain severity, frequency and chronicity. Mao et al. also pointed out that this investigation was not able to necessarily discern between individuals with quiescent or active inflammatory bowel disease (IBD), and appropriately concluded that this made it difficult to determine why patients in this study were receiving antispasmodics, and whether particular sub-cohorts (e.g., those with quiescent IBD and concomitant irritable bowel syndrome (IBS)) would demonstrate better outcomes after receiving these therapies. Additionally, they noted that almost two thirds of the patients included in our study did not report a racial identity. They also mentioned that there was a lack of information about participant socioeconomic status and education level. We appreciate all of these criticisms, and agree that they are all worthy of consideration. Indeed, as stated in our Discussion, there are important issues directly related to the use of retrospectively abstracted claims data that limit the inferences that can be made about this topic. In our Conclusions, we advocated for follow-on prospective studies to help address the limitations noted above.

Despite these concerns, we believe this study is important for several reasons. It is the first large-scale study investigating the clinical impact of antispasmodics in IBD. While there were potential limitations related to data type and quality, the database utilised has served as one of the largest and most comprehensive sources of information in the world for population-based studies and includes data from a wide variety of healthcare centres located around the world [3]. Thus, it is likely that the associated study cohort provided a ‘real-world’ assessment of antispasmodic provision and its impact in IBD. As stated above, Mao et al. suggested that antispasmodic use is more likely to be successful in patients with quiescent IBD who exhibit visceral hypersensitivity or IBS. It is important to note that there is no definitive evidence in IBD to support this statement. This is, in fact, one of the reasons we undertook this study. However, even if that statement is eventually determined to be accurate, previous investigations demonstrate that, when healthcare providers believe that patients with IBD are in remission, many harbour unrecognised inflammation and other factors (unrelated to IBS or visceral hypersensitivity) that may contribute to abdominal pain [4, 5]. Thus, identifying the optimal target population proposed by Mao et al. is still very challenging in practice (and in research). All of this makes our findings relevant to modern-day IBD providers and patients and reinforces the need for further careful study of this topic.