Open Label Ustekinumab for the treatment of anti-TNFα refractory moderate-to-severe Crohnʼs disease: Follow up of a cohort of patients at an academic inflammatory bowel disease center

Abstract

Purpose: Ustekinumab is a monoclonal antibody against the shared p40 subunitof interleukin-12/23, which has been demonstrated to produce clinical responsein patients with moderate-to-severe Crohn's disease (CD) with induction dosing in a phase 2a study. Since its approval by the FDA in September 2009 for the treatmentof psoriasis, the drug has been used off-label as a treatment for anti-TNFarefractory CD outside the context of clinical trials. This series describes post-marketinguse of ustekinumab in patients with moderate-to-severe CD at an academicmedical center. Methods: Patients were identified who had received at least 2 doses of ustekinumabfor the treatment of moderate-to-severe Crohn's disease. Patients received45 mg or 90 mg subcutaneous doses at weeks 0 and 4 and then were dosed atintervals of 8 or 12 weeks at the physician's discretion. Baseline demographicswere recorded and Harvey Bradshaw Index (HBI) was prospectively recorded oneach patient. The primary endpoint was clinical response, defined by a decreasein HBI < 3 at week 12. Secondary endpoints included remission (HBI < 3) andability to taper steroids at week 12. Results: A total of 21 patients met inclusion criteria and 15 patients have been ontherapy >12 weeks. Prior infliximab use and subsequent failure was documentedin 18/21 (86%) of patients with 8/18 (44%) having had failed 10 mg/kg dosing. 4/18 (22%) were considered to be infliximab primary non-responders. Additionally, 16/21 (76%) had failure to two or more anti-TNFa formulations. None of thepatients were on concurrent immunomodulator therapy with ustekinumab. Meanduration of ustekinumab was 28.8 6 16.6 weeks. At week 12, clinical response wasfound in 11/15 (73.3%) patients. Clinical remission was achieved in 8/15 (53.3%) atweek 12. Five patients were on steroids prior to initiation of ustekinumab; all fivewere able to taper their steroids by week 12 and one was able to discontinue steroidscompletely by week 8. No adverse drug reactions were noted. Conclusion: Ustekinumab is a promising therapy for moderate-to-severe Crohn'sdisease in patients who have previously failed anti-TNFa therapy. Further studiesexploring optimal dosing regimens for induction and longer-term studies onmaintenance are needed