Real-World Experience with Tofacitinib in IBD at a Tertiary Center

Abstract

Background and aims: Many inflammatory bowel disease (IBD) patients do not respond to medical therapy. Tofacitinib is a first in class, partially selective inhibitor of Janus kinase, recently approved for treating patients with ulcerative colitis (UC). We describe our experience with the use of tofacitinib for treatment of patients with moderate-to-severe IBD. Methods: This is a retrospective, observational study of the use of tofacitinib in IBD. Patients with medically resistant IBD were treated orally with 5 mg or 10 mg twice daily. Clinical response and adverse events were assessed at 8, 26, and 52 weeks. Objective response was assessed endoscopically, radiologically, and biochemically. Results: 58 patients (53 UC, 4 Crohn’s, 1 pouchitis) completed at least 8 weeks of treatment with tofacitinib. 93% of the patients previously failed treatment with anti-TNF. At 8 weeks of treatment, 21 patients (36%) achieved a clinical response, and 19 (33%) achieved clinical remission. Steroid-free remission at 8 weeks was achieved in 15 (26%) patients. Of the 48 patients followed for 26 weeks, 21% had clinical, steroid-free remission. Of the 26 patients followed for 12 months, 27% were in clinical, steroid-free remission. Twelve episodes of systemic infections were noted, mostly while on concomitant steroids. One episode of zoster infection was noted during follow up. Conclusions: In this cohort of patients with moderate-to-severe, anti-TNF resistant IBD, tofacitinib induced clinical response in 69% of patients. 27% were in clinical, steroid-free remission by one year of treatment. Tofacitinib is an effective therapeutic option for this challenging patient population.

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry

“…Several factors may contribute to this observation, including the relative shorter duration of follow‐up, the intention‐to‐treat design as well as corticosteroid taper for a subgroup of patients during follow‐up. Indeed, other real‐life cohort confirmed this finding (week 8 clinical remission 33%, week 26:25%) . To date, only two real‐world retrospective cohorts have reported the effectiveness and safety of patients receiving tofacitinib before market authorisation.…”

“…A single‐centre cohort study reported 58 patients (93% anti‐TNF and 81% vedolizumab exposed) treated with tofacitinib. After 26 weeks of treatment, 21% was in corticosteroid‐free clinical remission (physician global assessment) . In a compassionate early‐access programme in France, 38 patients received tofacitinib after failure of both anti‐TNF and vedolizumab treatment.…”

“…To date, only two cohort studies are available that describe the use of tofacitinib in daily practice . However, these cohorts are limited by the small population size and their retrospective nature.…”

COVID-19 and immunomodulation in IBD

“…15 Moreover, tofacitinib has an increased risk for certain viral infections (eg, herpes zoster infection). [59][60][61] Thus, treatment indication needs to be discussed in individual cases. At this point, no evidence for stopping these treatments in patients with remission exists.…”

Review article: prevention, diagnosis and management of COVID‐19 in the IBD patient

“…Of 4789 patients treated with tofacitinib in phase II, III and LTE studies, 259 patients had serious infections (3.09 events per 100 PY [95% CI 2.73, 3.49]), and the most common infection was pneumonia 92 . Higher doses of 10 mg twice daily as opposed to 5 mg twice daily, age >65 years, corticosteroids >7.5 mg/d and diabetes were also independent factors associated with increased serious infection risk 92,93 . Therefore, patients on tofacitinib should be maintained on the lower 5 mg twice daily dose compared to 10 mg twice daily where possible and weaned off corticosteroids.…”