Background: Efficacy of ustekinumab (UST) in Crohn's disease (CD) has been demonstrated in clinical trials. Real world symptomatic and endoscopic response is lacking. As opposed to intravenous (IV) induction, high dose subcutaneous (SC) induction has been proposed while the IV formulation is unavailable.
Methods: A retrospective, observational study of 2 different induction regimens was conducted. Standard dosing was 90mg SC at Week 0, 1 and 2; higher dose induction 270mg SC at Week 0 and 180mg SC at Weeks 1 and 2. Maintenance dosing was 90mg SC every 8 weeks for both induction regimens. Response assessed after 3 months (short term), and if remaining on therapy, after 6–12 months (medium term) and at least 12 months (long term). Symptomatic response defined as physician documentation of improvement of CD-associated symptoms, withdrawal of steroids and continuation of therapy. Endoscopic or radiological response defined as resolution or improvement in extent and severity of lesions.
Results: Seventy-nine patients commenced UST for CD from September 2012 to November 2016.(Figure 1) Five patients were lost to follow-up, with 74 patients remaining, including 39 induced with higher dose (Table 1). Maintenance dose escalation occurred in 17 patients (90mg every 4 weeks), of whom 13 and 4 had received standard and high induction. Symptomatic response assessed in 66 patients; 51% (17/33) in standard and 67% (22/33) in higher induction groups had short term symptomatic response. Biochemical response was seen in 64% (9/14) and 58% (11/19) of patients in standard and higher induction groups. Within the first 3 months, 29% (10/35) of standard and 8% (3/36) of higher induction groups ceased therapy. Symptomatic response was reported in 68% (15/22) of standard and 57% (13/23) of higher induction groups who continued on UST in medium term; in long term, 64% (14/22) and 80% (4/5) have an ongoing response. Endoscopic or radiologic response or improvement was achieved in 50% (10/20) and 71% (12/17) of standard and high induction groups. Of primary and secondary anti-TNF non-responders, 88% (14/16) and 56% (18/32) had short term symptomatic response.
Conclusions: Fifty-nine percent of patients had short term symptomatic response, with greater proportion receiving higher induction strategy, while primary non-response to prior anti-TNF was also associated with response. Fewer patients receiving high dose induction required dose escalation. Endoscopic or radiologic assessment also demonstrated greater improvement or response within this novel induction group. Results provide further encouragement for therapeutic benefit of UST in CD.