Spotlight on Janus kinase inhibitors

Recent studies assessed speed of response to upadacitinib in Crohn's disease, compared upadacitinib and tofacitinib for ulcerative colitis, and judged the effectiveness and safety of tofacitinib in older patients with ulcerative colitis.

Multiple recent studies looked at the efficacy of Janus kinase inhibitors in inflammatory bowel disease.

The first, published by Clinical Gastroenterology and Hepatology on March 14, was an industry-funded, post hoc analysis of multiple trials of upadacitinib. It assessed the rapidity of symptomatic improvement in patients with Crohn's disease who began therapy with upadacitinib, 45 mg once daily. AbbVie funded the trial and participated in its design, research, analysis, data collection, data interpretation, review, and publication approval. Based on daily diary data from 1,021 patients (674 on the drug, 347 on placebo), upadacitinib showed significant improvement in very soft/liquid stool frequency and abdominal pain score, providing relief by day 5 or 6, regardless of prior biologic exposure. Differences in these outcomes between the drug and placebo were significant at week 2 and maintained through week 12. Clinical remission began sooner with upadacitinib than with placebo (13 days vs. 32 days) and was more likely at week 2 (21.1% vs. 8.9%; P≤0.01). "In conclusion, patients with [Crohn's disease] may benefit from a convenient therapy that provides quick improvement and early symptom resolution without the consequences of excessive or prolonged corticosteroid use," the study authors said.

The second study, published by the American Journal of Gastroenterology on March 12, compared the effectiveness of upadacitinib and tofacitinib for ulcerative colitis. The retrospective cohort study compared rates of steroid-free clinical remission and endoscopic response or remission at a year between 81 patients who initiated upadacitinib (30% prior tofacitinib exposure) and 74 who initiated tofacitinib (0% prior upadacitinib exposure). They found that upadacitinib was associated with significantly higher odds of steroid-free clinical remission (odds ratio, 3.01; 95% CI, 1.39 to 6.55) and there was no difference between the drugs on endoscopic response or remission. Treatment persistence was higher in the upadacitinib group, and adverse event rates were consistent with the safety profiles of the two therapies, the study authors noted. "These findings suggest that upadacitinib may be more effective at achieving [steroid-free clinical remission] of [ulcerative colitis] through one year of therapy compared to tofacitinib, though these results should be confirmed in larger cohorts," they concluded.

Finally, a study published by the American Journal of Gastroenterology on March 14 looked at the effectiveness and safety of tofacitinib among elderly ulcerative colitis patients. The retrospective cohort study was funded by an unrestricted research grant from Pfizer and used Veterans Affairs data to compare 158 patients (53 patients ≥65 years of age, 105 <65 years of age) who initiated tofacitinib. At 12 months, effectiveness was 50.94% in the older group and 33.33% in the younger group (P=0.032). The study also found that the most common reason for discontinuation of the drug was loss of response (22.64% in the older group, 43.81% in the younger group). "In conclusion, tofacitinib appears to work well in the elderly, a finding that has clinical significance and warrants further investigation considering the large proportion of elderly [ulcerative colitis] patients," the study authors wrote.