The Limitations of JAK Inhibitors When Treating IBS

In 2024, Pharmaceutical Executive reported on a survey that showed a significant number of patients suffering from irritable bowel disease (IBD) struggle to afford proper healthcare. According to the results, treatments became unattainable due to barriers such as financial challenges and insurance issues. Many patients also struggled with adverse health impacts.

At the time, the Crohn's & Colitis Foundation president and CEO Michael Osso said, “These findings underscore the urgent need to address healthcare disparities in IBD care. Despite our progress in IBD research and treatment options, many patients still struggle to access the care they need without facing undue burden. Our survey findings highlight the critical need for reforms to ensure that IBD patients can access the medications they need without undue financial hardship."

Recently, Pharmaceutical Executive spoke with Christian Thienel, director at Back Bay Life Sciences, about the ongoing issues with IBD treatments. While the original survey focused more on the financial barrers, Thienel’s conversation looked at treatment and R&D barriers which allow for persistent unmet needs to impact patients.

Pharmaceutical Executive: When treating IBD, what are the restraints with JAK inhibitors?
Christian Thienel: JAK inhibitors have been around for quite a while, and they are understood to be highly effective. The JAK-STAT pathway has a well-established role in autoimmune and inflammatory diseases — it is one of the most direct and well-characterized mechanisms in a space that attracts significant attention from large pharma.

Rinvoq — upadacitinib, AbbVie's product — has been very successful in IBD. It has strong data for inducing and maintaining clinical remission, and the oral delivery is a meaningful advantage. But what comes up consistently in our research is the safety concern — not just with Rinvoq specifically, which in many ways has a better safety profile than earlier JAK inhibitors, but with JAK inhibition as a class. There is a perception problem among physicians: JAK inhibition carries baggage from an adverse event standpoint that is difficult to separate from any individual product.

Rinvoq carries boxed warnings for cardiovascular adverse events, malignancy risk, and infection risk. And there have been other JAK inhibitors in this space that have faced regulatory challenges or significant labeling updates related to adverse events. That history colors how physicians think about the class as a whole.

What came through very clearly across our research is that if there were an oral product that matched Rinvoq's level of efficacy without those safety concerns, it would be a clear winner in this space. That said, Rinvoq is doing very well — it has grown tremendously in IBD, which speaks to the depth of unmet need for oral options in this space. Even with its limitations, it is used extensively and has an important clinical role. Virtually all of the KOLs we spoke with use it and are relatively satisfied with it. But awareness of the cardiovascular and broader safety risks remains acute, and that concern is consistently top of mind.