Comment on: Final results from the vedolizumab extended access program multinational study demonstrate long-term treatment persistence and safety

To the Editor,

We read with great interest the article by Danese et al. ¹ reporting the final results of the multinational vedolizumab extended access program (XAP), which provides valuable long-term data on treatment persistence and safety in patients with ulcerative colitis and Crohn’s disease previously enrolled in GEMINI LTS or VERSIFY. The study included 331 patients, most of whom initiated the XAP on every-8-week (Q8W) dosing, and showed high persistence without relapse at 6 months among those starting Q8W treatment. ¹ In addition, only 9% of patients required re-escalation from Q8W to Q4W dosing, and serious adverse events and serious infections were uncommon. ¹ These findings reinforce the favorable long-term therapeutic profile of vedolizumab in inflammatory bowel disease (IBD).

Nevertheless, we would like to highlight a methodological aspect that merits further discussion: the distinction between persistence and adherence. Although these concepts are closely related, they are not interchangeable. Persistence refers to the duration of time a patient remains on treatment, whereas adherence reflects the extent to which the prescribed dosing schedule is actually followed.^2,3 Failure to distinguish between both dimensions may lead to an overestimation of the real therapeutic value of long-term treatment continuation. Particularly with SC biologics, where self-administration places responsibility on the patient, the risk of administration errors or skipped doses may increase. Ignoring adherence in persistence studies may therefore result in biased or overly optimistic estimates of treatment effectiveness and safety.^4,5

In the multinational extended access program evaluating long-term vedolizumab treatment persistence and safety, persistence was assessed based on continued treatment within the study protocol. However, the study did not include a formal assessment of medication adherence prior to calculating persistence outcomes. Although treatment compliance was recorded during the study, this parameter was not incorporated into the persistence analysis nor used to validate dosing adherence over time. Consequently, persistence estimates reflect ongoing treatment exposure rather than confirmed adherence to the prescribed dosing schedule. Importantly, the absence of adherence data is not explicitly addressed in the limitations section, which mainly focuses on the open-label design and potential selection bias due to the inclusion of patients who had previously benefited from vedolizumab therapy. ¹

From a broader perspective, the growing importance of adherence aligns with the evolving 6P Medicine framework (Personalized, Predictive, Preventive, Participatory, Precision, and Persistent), which highlights persistence and adherence as essential components for optimizing chronic disease management and therapeutic outcomes.^5–7 Integrating adherence metrics into persistence analyses would provide a more comprehensive understanding of treatment utilization and improve the interpretability of real-world evidence in inflammatory diseases.

The study by Danese et al. ¹ provides encouraging evidence for the long-term therapeutic profile of vedolizumab in IBD. We strongly advocate for the routine inclusion of adherence measures in IBD studies evaluating treatment persistence with biologic therapies. This would ensure a more comprehensive understanding of real-world treatment dynamics and contribute to optimizing biologic therapy outcomes in IBD. Only by the selection of adherent patients previously can we fully assess the persistence therapeutic value of chronic biologic treatments and optimize outcomes for patients living with IBD.