# Editorial: real-world evidence of tofacitinib and vedolizumab in ulcerative colitis-are we one step closer to better positioning therapies after anti-TNF failure?

## Authors’ reply

Anthony Buisson

► To cite this version:

Anthony Buisson. Editorial: real-world evidence of tofacitinib and vedolizumab in ulcerative colitis-are we one step closer to better positioning therapies after anti-TNF failure? Authors’ reply. Alimentary Pharmacology & Therapeutics (Suppl), 2023, 57 (6), pp.735-736. 10.1111/apt.17405. hal-04056456

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Submitted on 3 Apr 2023

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# Editorial: real-world evidence of tofacitinib and vedolizumab in ulcerative colitis—are we one step closer to better positioning therapies after anti-TNF failure? Authors' reply

First of all, we would like to thank Drs Ernest-Suarez and Lu for their interest in our real-world comparison between tofacitinib and vedolizumab in patients with ulcerative colitis after failure of anti-TNF therapy.¹,² Drug sequencing is currently a burning question in inflammatory bowel disease, especially in ulcerative colitis owing to the growing number of available therapeutic classes with different mechanisms of action. Beyond crude efficacy, the impact of the therapeutic sequence, that is whether treatment A followed by treatment B achieves the same efficacy as the reverse sequence, is a major question. The STARTER project has been specifically built to answer this question and will start soon. It is a French multicenter randomised controlled trial comparing four therapeutic sequences in biologic-naïve UC patients. Each sequence will start with a different class of medication, that is anti-TNF agent, anti-integrin, anti-IL12/IL23 or JAK inhibitor.

To compare the efficacy of two drugs after anti-TNF failure, no head-to-head trials are currently available, and network meta-analyses rely on a low number of studies for each drug.³,⁴ Thus, real-world indirect comparisons adjusted using propensity scores are of great interest. In our work, the first message apply to vedolizumab. Contrary to what may sometimes be suggested, vedolizumab can lead to remission as soon as week 2 in one third of the patients. However, a longer period is required for some patients up to week 14, meaning that the time to observe response to vedolizumab can range from week 2 to week 14. In addition, we found that vedolizumab is less effective in case of more severe (Mayo score >6 and CRP >30) or more refractory (primary failure to at least biologic) UC. The second message concern tofacitinib. Contrary to vedolizumab, we did not find any factor associated with tofacitinib failure. Of note, we reported a very high rate of relapse after decreasing the dose from 10 to 5 mg b.i.d in patients achieving remission at week 8 (48%). This result should lead to caution before dose de-escalation in patients treated with tofacitinib. We also observed a delayed response (week 16) in one-quarter of patients receiving tofacitinib without any response at week 8, underlining that tofacitinib therapy should be maintained at least 16 weeks before considering therapeutic failure.

Finally, our data suggest that tofacitinib could be more effective than vedolizumab after anti-TNF failure in terms of endoscopic and histological remission. It is in line with the results of a Dutch cohort, showing that tofacitinib-treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at weeks 12, 24 and 52 compared with vedolizumab-treated patients.⁵

However, efficacy is not the only parameter impacting therapeutic decision-making. Except for the question of drug reimbursement by the healthcare system, which is highly different across the countries, the choice of the best therapy should rely on the triptych

<table><caption>TABLE 1 Arguments to choose between tofacitinib and vedolizumab after failure to anti-TNF therapy in patients with UC.</caption><thead><tr><th></th><th>Favouring tofacitinib</th><th>Favouring vedolizumab</th></tr></thead><tbody><tr><td>Efficacy<sup>2,5</sup></td><td></td><td></td></tr><tr><td>Rate of steroid-free clinical remission</td><td>✓</td><td></td></tr><tr><td>Rate of endoscopic remission</td><td>✓</td><td></td></tr><tr><td>Rate of histological healing</td><td>✓</td><td></td></tr><tr><td>Time to efficacy</td><td>✓</td><td></td></tr><tr><td>Severe UC</td><td>✓</td><td></td></tr><tr><td>Primary failure to at least one biologic</td><td>✓</td><td></td></tr><tr><td>Joint extra-intestinal manifestations</td><td>✓</td><td></td></tr><tr><td>Safety<sup>4,7</sup></td><td></td><td></td></tr><tr><td>Risk of cardiovascular events</td><td></td><td>✓</td></tr><tr><td>Risk of thromboembolism events</td><td></td><td>✓</td></tr><tr><td>Risk of lung neoplasm</td><td></td><td>✓</td></tr><tr><td>Age > 65 years-old</td><td></td><td>✓</td></tr><tr><td>Comorbidities</td><td></td><td>✓</td></tr><tr><td>Acceptability<sup>6</sup></td><td>✓</td><td></td></tr></tbody></table>

AP&T correspondence columns are restricted to invited editorials and letters discussing papers that have been published in the journal. An invited editorial or letter must have a maximum of 500 words, may contain one table or figure, and should have no more than 10 references. It should be submitted electronically to the Editors via http://mc.manuscriptcentral.com/apt.
efficacy-safety-acceptability.⁶ The arguments for favouring tofacitinib or vedolizumab after anti-TNF failure are summarised in Table 1.

## AUTHOR CONTRIBUTIONS

**Anthony Buisson:** Conceptualization (lead); writing – original draft (lead).

## ACKNOWLEDGEMENTS

*Declaration of personal interests:* The authors' declarations of personal and financial interests are unchanged from those in the original article.²

## LINKED CONTENT

This article is linked to Buisson et al papers. To view these articles, visit https://doi.org/10.1111/apt.17305 and https://doi.org/10.1111/apt.17351

Anthony Buisson¹,² ID

¹Université Clermont Auvergne, Inserm, CHU Clermont-Ferrand, 3iHP, Service d'Hépato-Gastro Entérologie, Clermont-Ferrand, France

²Université Clermont Auvergne, 3iHP, Inserm U1071, M2iSH, USC-INRA 2018, Clermont-Ferrand, France

## Correspondence

Anthony Buisson, Université Clermont Auvergne, Inserm, CHU Clermont-Ferrand, 3iHP, Service d"Hépato-Gastro Entérologie, Clermont-Ferrand, France.

Email: a_buisson@hotmail.fr

## ORCID

Anthony Buisson ID https://orcid.org/0000-0002-6347-409X

## REFERENCES

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2. Buisson A, Nachury M, Guilmoteau T, Altwegg R, Treton X, Fumery M, et al. Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent. Aliment Pharmacol Ther. 2023;57(6):676-88. https://doi.org/10.1111/apt.17305

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