Upadacitinib and tofacitinib are both JAK inhibitors (JAKis) approved by the FDA for the treatment of ulcerative colitis. In this interview with Expert Faculty member Prof. Gil Y. Melmed (Cedars-Sinai, Los Angeles, CA, USA) we discuss the aims, design and findings from his study presented at DDW 2023, comparing the efficacy and safety of these JAKis.
The abstract ‘COMPARATIVE EFFICACY AND SAFETY OF UPADACITINIB VERSUS TOFACITINIB AS INDUCTION THERAPY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: A MATCHING-ADJUSTED INDIRECT COMPARISON‘ (Abstract number: Su1720) was presented at Digestive Disease Week 2023, May 6-9, 2023.
- What impact has the approval of JAK inhibitors already had on the treatment paradigm for moderately to severely active ulcerative colitis? (0:17)
- What were the aims and design of your study comparing upadacitinib and tofacitinib? (1:32)
- What were the comparative safety and efficacy findings during induction treatment? (3:11)
- How will these insights optimise the use of JAK inhibitors in this indication? (3:41)
Disclosures: Gil Melmed discloses consulting for Abbvie, Amgen, Arena, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Janssen, Gilead, Genetech, Pfizer, Samsung Bioepis, Takeda, Shionogi, Prometheus Labs, Techlab, Fresenius Kabi, and Viatris; and receiving grant/ research support from Pfizer.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Victoria Jones.
Filmed in coverage of Digestive Disease Week 2023.
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What impact has the approval of JAK inhibitors already had on the treatment paradigm for moderately to severely active ulcerative colitis? (0:17)
JAK inhibitors were introduced for the treatment of ulcerative colitis with the introduction of tofacitinib a few years ago, and then more recently with upadacitinib last year, and they certainly have made their way into the treatment paradigm, although in a perhaps an anticipated/limited, more limited way with the introduction of a boxed warning by regulatory agencies that these agents can only be used after a patient has tried an anti-TNF drug, at least in the US. And, really, that has placed the utilization of JAK inhibitors as second-line therapy behind anti-TNF or perhaps third-line therapy if a patient is not initially on an anti-TNF as an advanced drug, and that has, you know, somewhat limited the uptake of JAK inhibitors, unfortunately, in my opinion, because these drugs seem to have remarkable efficacy as well as overall very favourable safety profile for our younger patients with inflammatory bowel disease, specifically in this case ulcerative colitis.
What were the aims and design of your study comparing upadacitinib and tofacitinib? (1:32)
We performed a matching adjustment – matching adjusted – indirect comparison of clinical trials using clinical trial data for upadacitinib relative to tofacitinib and also looked at another drug ustekinumab in a separate study that we presented at DDW. What this study was about was really to utilize a technique of network meta-analysis, which allows for indirect comparisons across clinical trials, and by way of trying to normalize the control group, the placebo groups, utilizing specific patient characteristics and parameters that are matched. We try to establish the most homogeneous kinds of associations by comparing one trial to another and and being able therefore to draw indirect comparisons. If study A looks at one drug versus placebo and study B looks at a different drug versus placebo, and then we can somehow match and say that those placebo arms are relatively similar and the patient populations are relatively similar, we can draw then indirect comparisons both on the efficacy side and on the safety side between the two different drugs. That being said, you know, this is not an overall randomized controlled trial. It’s indirect comparisons with published data of different trials, and each trial certainly has its own unique nuances that in general make it more difficult to compare across trials, so this is one technique to try to overcome that bias.
What were the comparative safety and efficacy findings during induction treatment? (3:11)
So we found that upadacitinib had relatively greater efficacy compared to tofacitinib during induction as well as relative superiority relative to ustekinumab during induction. And so, we, again, we’re doing this using this matching adjusted indirect comparison using a network meta-analysis technique.
How will these insights optimise the use of JAK inhibitors in this indication? (3:41)
Well, I think one big question becomes when a patient is ready for a JAK inhibitor or when it’s appropriate to introduce a JAK inhibitor now that we have options for which JAK inhibitor to prescribe, we need to understand potential relative differences between them. There may be differences in cost, there may be differences in convenience in terms of, for example, how many pills a day, there may be differences in efficacy, there may be differences in safety and so what we are trying to do is try to parse out those differences with available data that, you know, to the best of our ability, given the lack of direct head to head comparison trials.
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