JAK inhibitors show fast results, improved QOL, low adverse events in IBD
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MAUI, Hawaii — JAK inhibitors offer quick results, improved quality of life and lower serious adverse events for patients with inflammatory bowel disease, according to an expert at the GUILD Conference 2020.
“JAK inhibition represents a potent, fast-acting mechanism of action,” Edward V. Loftus Jr, MD, professor of medicine at the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minnesota, said during his presentation. “Tofacitinib [Xeljanz, Pfizer] is approved for moderate-to-severe UC in patients who have failed anti-TNFs. The selective JAK1 inhibitors appear very promising in [Crohn’s disease], upadacitinib [Rinvoq, AbbVie] specifically, we have data in UC and that appears to be advantageous.”
In two OCTAVE induction studies with patients with moderate-to-severe UC, tofacitinib did 10 percentage points better than the placebo-treated patients. In both studies, patients had higher clinical responses to tofacitinib (59.9% and 55%) than the placebo (32.8% and 29%).
Loftus said patients respond more quickly with tofacitinib, with a post-hoc analysis of individual patient-reported symptom scores showing differences in rectal bleeding and stool frequency as early as 3 days after being treated with tofacitinib. Patients treated with filgotinib (Gilead) had higher clinical remission (47%) and response reduction (59%) than placebo-treated patients (23% and 41%).
Health related QOL improved due to reduction of disease symptoms. Using the Inflammatory Bowel Disease Questionnaire, these studies showed the average score for patients treated with tofacitinib improved by 20 points in OCTAVE 1, 30 points in OCTAVE 2 and in OCTAVE Sustain, the tofacitinib cohort maintained health related QOL while the placebo cohort reported a diminished QOL score.
For safety, patients treated with upadacitinib reported lower incidence of serious adverse events (5% to 28%) and serious infections (0% to 8%). Tofacitinib had a low incidence of herpes zoster with an overall incidence of four per 100 person-years.
“In my practice, I would just make patients aware of the zoster vaccine,” Loftus said. “I would not require them to get the vaccine before they go on tofacitinib because in the induction trial there was no zoster risk for 8 weeks. That’s going to happen later on, so you have time to give the vaccine.”
Researchers are currently developing a phase 3 trial of Crohn’s disease and UC to obtain more data on filgotinib and upadacitinib JAK inhibitors. – by Erin T. Welsh
Reference: Loftus EV. JAK Inhibitors Users Guide. Presented at: GUILD Conference 2020; February 16-19, 2020; Maui, Hawaii.
Disclosures: Loftus reports consulting for AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Pfizer, Takeda and UCB Pharma; and research support from AbbVie, Amgen, Celgene, Genentech, Gilead, Janssen, MedImmune, Pfizer, Robarts Clinical Trials, Seres Therapeutics, Takeda, and UCB Pharma.