Letter: Toward Intra-Class Switching With JAK Inhibitors? Authors' Reply

We thank Dr. Uzzan et al. [1] for their comments on our publication [2]. We have clarified the data availability regarding intra-class switching with Janus kinase (JAK) inhibitors in our study (Figure 1). We demonstrated the efficacy of upadacitinib in ulcerative colitis (UC) after the use of tofacitinib and filgotinib [2]. As a result, upadacitinib-treated patients showed a clinical remission rate of 71.9% (64/89) at the most recent follow-up (median 53 weeks). This suggests that upadacitinib can be considered after the use of tofacitinib or filgotinib. Given the highest efficacy of upadacitinib among the three JAK inhibitors in UC [2], opposite approaches may not be reasonable. We also assessed the efficacy of filgotinib after the use of other JAK inhibitors, predominantly tofacitinib [2, 3]; filgotinib-treated patients showed a clinical remission rate of 50% (10/20) at the most recent follow-up (median 52 weeks) [2]. Our results also indicate that filgotinib could offer a chance to achieve remission in patients previously exposed to tofacitinib.

FIGURE 1

Open in figure viewerPowerPoint

Data availability regarding intra-class switching with Janus kinase (JAK) inhibitors in our study. The red arrow indicates data that were analysed, while the black dotted arrow indicates the lack of data in this study.

As Dr. Uzzan et al. [1] pointed out, we did not evaluate the efficacy of tofacitinib in patients who had previously been treated with other JAK inhibitors as we primarily collected data from patients who started JAK inhibitors within the first 18 months following the approval of each drug in Japan. Tofacitinib was approved in 2018 as the first JAK inhibitor for UC; therefore, there were no data on its efficacy following upadacitinib or filgotinib, which were approved in 2022. To the best of our knowledge, there have been no real-world data specifically addressing this issue, and the number of comparative studies between tofacitinib and filgotinib is also limited.

Our comparative analysis using propensity score matching showed that some clinical outcomes (e.g., clinical response at 10 and 26 weeks, as well as endoscopic improvement) appeared to be better with tofacitinib than with filgotinib, although the differences were not statistically significant. In addition, Yagi et al. [4] showed that tofacitinib was more effective than filgotinib at 8 weeks for patients with UC who did not respond to therapy within the first 4 weeks. These findings suggest that tofacitinib may be more effective than filgotinib for UC and could be considered an option for patients previously treated with filgotinib. We agree that more data are needed to better understand the cycling strategy within JAK inhibitors in UC, and we look forward to seeing the data from the European Crohn's and Colitis Organisation [1].

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].