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Clinicians often face uncertainty in deciding when and how to position biologics versus Janus kinase (JAK) inhibitors in anti-tumor necrosis factor (TNF) therapy-refractory patients with ulcerative colitis (UC). To shed light on this dilemma, Marjolijn Duijvestein, MD, of Amsterdam University Medical Center in the Netherlands, and colleagues compared the relative effectiveness and safety of vedolizumab (Entyvio) and the JAK inhibitor tofacitinib (Xeljanz) in anti-TNF-exposed UC patients in the Dutch Initiative on Crohn and Colitis (ICC) Registry.

The results were recently published in , and Duijvestein discussed the study with the Reading Room.

What were the clinical indicators that led to your group's undertaking this comparative analysis?

Duijvestein: In the last couple of decades, several new therapeutic options for UC became available -- all with similar efficacy rates. Since head-to-head trials are scarce, optimal positioning of biologics and JAK inhibitors in the therapeutic strategy remains an area of ongoing research. One of the challenges in the treatment of UC is that we cannot predict which patient is going to respond to a certain therapy, and until now, there has been a lack of head-to-head trials directly comparing the efficacy rates of these relatively new treatment options. Therefore, we compared the effectiveness and safety of tofacitinib with vedolizumab in an observational prospective cohort.

What was the specific knowledge gap you wished to fill?

Duijvestein: We wanted to determine whether tofacitinib was as effective as vedolizumab or even more effective. In UC patients failing anti-TNF therapies, we often do not know which biologic therapy or small molecule we should initiate. It was thought that the outcomes of this study might help guide clinical decision making in patients failing anti-TNF.

Who was included in the study cohort?

Duijvestein: We used the Initiative on Crohn and Colitis (ICC) Registry, a nationwide prospective cohort that includes inflammatory bowel disease (IBD) patients starting on novel IBD therapies. Analysis of this cohort aims to describe the long-term effectiveness and safety of the novel IBD drugs now used in everyday care in the Netherlands. It also tries to identify predictors of response.

The ICC Registry had a prospective follow-up with visits designed to closely follow standard clinical care. Visits occurred at initiation of therapy, at week 12, week 24, and week 52. Currently, 19 centers throughout the Netherlands participate in the ICC Registry.

For this study, we included patients who were anti-TNF-experienced, but vedolizumab- and tofacitinib-naive and who exhibited clinical and either biochemical or endoscopic disease activity.

What were the principal findings and did any surprise you?

Duijvestein: We found that tofacitinib was superior to vedolizumab in achieving corticosteroid-free clinical and biochemical remission after 12, 24, and 52 weeks of treatment. The safety profiles were comparable in both treatment groups.

This difference in effectiveness was also seen in previous meta-analytic research. We expected to see more of a difference in the safety profiles. Vedolizumab is known to be a very safe therapy in contrast to tofacitinib, which may cause thromboembolic or cardiovascular events.

As for predictors of response, in univariate analysis there were none in vedolizumab-treated patients. In tofacitinib-treated patients, shorter disease duration at initiation of therapy was associated with corticosteroid-free clinical remission at week 52.

Do the results align with other research and what you see in your clinical practice?

Duijvestein: This is the first study assessing the comparative effectiveness of tofacitinib and vedolizumab. However, our results do align with the data we have from meta-analyses. The effectiveness rates in this cohort slightly differed from the efficacy rates in phase III trials.

What are the immediate clinical implications of the findings?

Duijvestein: Our results might guide clinical decision making in patients failing anti-TNF therapies. With these results in mind, we might be more prone to initiate tofacitinib in patients with a low risk profile for adverse events.

Are there any unanswered questions or study limitations that need to be addressed?

Duijvestein: Our finding that the safety profiles of tofacitinib and vedolizumab were comparable contrasts with that of previous studies and experience in the field of rheumatology.

In our study, the follow-up was only 1 year and longer follow-up is required. There may also have been some selection bias in patients initiating vedolizumab and not tofacitinib. Therefore, we cannot yet make firm statements about safety profiles.

You can read the abstract of the study here, and about the clinical implications of the study here.