Editorial: Dual Advanced Therapy in Refractory Ulcerative Colitis—Hope Beyond Monotherapy. Authors' Reply

We read with great interest the editorial by de Boer et al.; that acknowledged the growing role of dual advanced therapy (DAT) in managing refractory ulcerative colitis (UC) [1]. We appreciate the recognition of our study investigating the combination of vedolizumab and tofacitinib (VETO) in patients who had failed both anti-TNF agents and a second-line advanced therapy.

As mentioned, monotherapy often falls short in patients with refractory UC in whom multiple advanced therapies had failed, necessitating novel approaches. Combination therapy of an anti-TNF agent with a thiopurine demonstrated improved outcomes in SONIC and UC SUCCESS [2, 3]. However, concerns regarding infections and malignancy risks have limited its long-term use [4]. Our VETO study showed promising clinical response (71%) and remission (58%) at 24 weeks, without any therapy-limiting adverse events, indicating the potential utility of well-selected DAT regimens in this population [5].

The editorial raised an important concern regarding affordability and accessibility, particularly in low- and middle-income countries. Here, we would like to highlight that biosimilars for agents such as adalimumab, infliximab, ustekinumab and tofacitinib are already available in India, and vedolizumab biosimilars are in the pipeline. This significantly reduces the cost of advanced therapy. The entry of these biosimilars into the Indian market has brought dual biologic or advanced therapy within the financial reach of many patients, even outside the insured or government-supported sectors [6].

Moreover, tofacitinib, being an oral Janus kinase inhibitor, offers unique logistical and economic advantages. Unlike infusion-based biologics, tofacitinib allows patients to avoid repeated hospital visits, leading to cost savings on travel, time and loss of productivity. This convenience further strengthens the role for combinations like VETO in resource-constrained settings [7, 8].

The authors also showed that current DAT data are mostly clustered in western settings; our study has broadened the global evidence base for DAT and was the first prospective study on the combination of vedolizumab and tofacitinib. Furthermore, the ongoing randomised DUET-CD and DUET-UC trials in, respectively, Crohn's disease and UC are expected to strengthen the role of DAT in IBD management [9, 10].

Nevertheless, prudent patient selection always remains key. Long-term safety, immunogenicity, pharmacokinetics and cost-effectiveness have to be further evaluated. DAT can be considered in patients with refractory disease—ideally under multidisciplinary care at centres of excellence until more data emerge allowing us to position this appropriately in managing UC.

In summary, we agree with the authors that DAT represents an emerging frontier in IBD care. With improving drug access through biosimilars and the practical advantages of oral molecules like tofacitinib and upadacitinib, DAT may soon be a feasible and sustainable option.

Pardhu Bharath Neelam: writing – review and editing, writing – original draft. Rupa Banerjee: supervision, conceptualization, writing – review and editing.

The authors declare no conflicts of interest.

This article is linked to Neelam et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70309 and https://doi.org/10.1111/apt.70318.

The data that support the findings of this study are available from the corresponding author upon reasonable request.