Abstract
Dear Editor,
We read with great interest the recent article entitled “Prevalence, patient characteristics, and outcomes of high-dose upadacitinib in inflammatory bowel disease” by Azar et al. 1 which evaluates high-dose upadacitinib maintenance therapy in patients with refractory inflammatory bowel disease. The authors should be commended for their valuable real-world investigation, offering important insights on the efficacy and safety of high-dose upadacitinib in a particularly challenging patient population.
However, we would like to raise two points which could further strengthen the interpretation of the findings. First, authors reported promising clinical results with high-dose upadacitinib maintenance, but the large difference between clinical response and endoscopic remission needs to be considered further. Of the patients in the high-dose maintenance cohort, 73.7% achieved clinical response, while only 36.7% achieved endoscopic remission. This discrepancy suggests that symptomatic improvement may not necessarily be equated with complete control of the underlying intestinal inflammation. With mucosal healing becoming an important therapeutic goal in current management of inflammatory bowel disease, sole dependence on clinical response may overestimate the actual effectiveness of high-dose upadacitinib. A more detailed discussion of this discordance would have improved interpretation of the study findings and provided better insight into the long-term disease-modifying potential of high-dose maintenance therapy. 2
Second, patients receiving high-dose maintenance therapy were more likely to be treated with concomitant biologics, which may have affected the reported results. Therefore, upadacitinib cannot be the only cause of the reported clinical benefits. As biologic agents may contribute independently or synergistically to treatment response. Therefore, a subgroup analysis that excludes patients receiving concurrent biologic therapy would help elucidate the true impact of high-dose upadacitinib. 3 Despite these considerations, the study provides a strong foundation for further research in optimizing treatment strategies in refractory inflammatory bowel disease.
