JAK inhibitors: ‘A valuable addition’ to the IBD treatment portfolio
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This month’s Healio Exclusive highlights the efficacy of Janus kinase inhibitors in the management of ulcerative colitis and Crohn’s disease.
For UC, we have here in the U.S. both Xeljanz (tofacitinib, Pfizer) and Rinvoq (upadacitinib, AbbVie), and for CD we have upadacitinib. Filgotinib is available for UC in Europe and Japan. These agents reduce inflammation via multiple effects.
As outlined in the article, they are orally delivered, potent and rapidly acting. The drugs seem to also be effective in patients who have already been exposed to advanced therapies. Those of us who utilize this class of drugs have stories of patients who have failed multiple lines of therapy and yet have had dramatic responses with a JAK inhibitor.
The high potency and rapid onset of action raise the possibility that these drugs can be used like corticosteroids to rapidly extinguish symptoms — if rapid access to the drug can be ensured, of course. There are emerging data that upadacitinib may also be effective in perianal fistula healing.
One potential barrier to the use of this class is safety. Most of us are familiar by now with the ORAL Surveillance study examining the comparative safety of tofacitinib and anti-TNF agents in older patients with rheumatoid arthritis and cardiovascular risk factors. The results of this study led to additional safety warnings by the FDA on the whole class of JAK inhibitors for all indications, regarding cardiovascular events, thromboembolism and malignancy. Furthermore, the use of this class was restricted to patients who had already been treated with an anti-TNF agent.
Secondary analyses of the ORAL Surveillance study suggest that in patients younger than 65 years who have never smoked cigarettes, there may be no increased risk for these side effects relative to anti-TNF agents.
Whether these safety concerns apply to inflammatory bowel disease patients, younger patients and those on JAK inhibitors other than tofacitinib remains unclear.
As is mentioned in the article, the efficacy and safety issues here are reminiscent of where we were over two decades ago with Remicade (infliximab, Janssen). My own take is that one only has to see the rapid onset and magnitude of efficacy a few times in patients to understand the power of this class.
Our group has been fortunate enough to be involved in clinical trials of three of these agents over the past 12 years or so, and we feel very comfortable prescribing these agents. My own anecdotal experience is that the drugs are well-tolerated in most patients. Complete blood count and hepatic panel monitoring every 3 months is a good idea, and periodic monitoring of the lipid panel is worthwhile. Recombinant zoster vaccine is also a good idea.
With time, one’s comfort level with prescribing this class of drugs will increase significantly, resulting in a valuable addition to your toolbox.
- Reference:
- Ytterberg SR, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2109927.
- For more information:
- Edward V. Loftus Jr., MD, is the Maxine and Jack Zarrow Family Professor of Gastroenterology at the Mayo Clinic and chief medical editor of Healio Gastroenterology. He can be reached at loftus.edward@mayo.edu.
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