Beyond first-line biologic therapy: does treatment sequence matter in ulcerative colitis?

advantage persisted despite subsequent treatment adjustments in both groups.Most importantly, subsequent treatment did not fully compensate for a less effective initial strategy.Although most patients in the ABS group subsequently received infliximab or vedolizumab as second-line therapy, the difference in disease control persisted, suggesting that delayed use of an effective therapy may not be equivalent to its early use.The SLIT-UC study by Galts et al. 4 similarly demonstrated a lower clinical response at 1 year when infliximab was used as second-line or later therapy than when it was used as first-line therapy.However, this effect may not be universal across therapeutic sequences, as data from the UK IBD BioResource showed preserved effectiveness of anti-tumor necrosis factor therapy after vedolizumab failure.5 Together, these findings suggest that the impact of therapeutic sequencing may depend on the individual agent and preceding treatment rather than simply the number of prior therapies.With the recent expansion of therapeutic options for UC, advanced therapies now extend well beyond the biologics evaluated in the APPETISER study to include small molecules and newer biologic agents.Recent network meta-analyses suggest that upadacitinib ranks among the most effective therapies, while newer interleukin-23 inhibitors, including risankizumab and guselkumab, also demonstrate high efficacy.6 The emergence of highly effective oral agents such as upadacitinib may blur the traditional distinction between effective-