Journal Article

Ustekinumab Reinduction for Loss of Response or Interruption of Treatment

Scoville, Elizabeth, Bennett, Audrey L, Beaulieu, Dawn B, Schwartz, David, Garrett, Ailish, Annis, Kim, Duley, Caroline, Wagnon, Julianne, Dalal, Robin, Horst, Sara N, Evers, Lauren

2018

Overview

Introduction: Ustekinumab (UST) has been shown to be an effective treatment for maintenance and remission in patients (pts) with moderate to severe Crohn's disease (CD). We aim to evaluate our single center experience with re-induction using subcutaneous (SQ) or intravenous (IV) UST to recapture response and maintain treatment in a subset of pts with refractory CD who had failed prior anti-TNF therapy. Methods: Most pts started UST prior to FDA approval and received induction of UST SQ using novel dosing with UST 90mg SQ at weeks 0, 4, and 12. A majority of pts also received a 270 mg dose at wk 8 of induction (insurance approval dependent). Standard maintenance therapy was 90mg SQ every 8 weeks. If pts had re-induction with UST prior to FDA approval of UST for CD they had a modified re-induction (270mg SQ). After FDA approval, pts received IV doses for re-induction. Statistical analysis was performed using Wilcoxon rank sum testing. Results: 34 pts with CD underwent re-induction with UST. Table 1 summarizes pt characteristics. All pts had been on prior anti-TNF. Total follow up available was 850 days (d) (range 359, 2309 d). Only 2 pts had started UST after FDA approval for use in CD and had IV induction. Reasons for re-induction are summarized in Table 2. 21 pts had a modified re-induction with 270mg SQ dose and 13 pts had IV re-induction. Pts were followed for a median 440 d (range 64, 2196 d) after re-induction. For those with IV re-induction (n=13), follow up was median 282 d (64, 605 d). Only 4 pts discontinued UST after SQ re-induction, at a median of 152 d (118, 210 d) after re-induction. No pts who had IV re-induction had stopped UST by the end of study. 13 pts went to every 4-6 week dosing (4 of those pts with IV re-induction). HBI, CRP decreased in all pts. In 11 pts with IV re-induction, HBI decreased significantly (p <0.05). (Table 3) Ustekinumab levels prior to IV re-induction (n=5) were 1.6ug/mL (0.4, 4.9). 2 pts had levels drawn after re-induction (0.7ug/mL and 3.6ug/mL). 5 pts who had endoscopic inflammation on prior endoscopy were found to be in endoscopic remission, 2 pts had improvement, and 7 pts had no change endoscopically. Conclusion: In summary, re-induction with UST in pts with moderate to severe CD with anti-TNF failure may be an option to recapture response if stopped for loss of response or another reason, such as surgery.

• Publisher: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Crohn's disease / Endoscopy / FDA approval / Gastroenterology / Monoclonal antibodies