Inflammatory Bowel Diseases, 2021, 27, 2031–2033 DOI: 10.1093/ibd/izab131 Advance access publication 18 June 2021 Brief Report - Clinical Received for publications: March 6, 2021. Editorial Decision: April 13, 2021 © 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Infiximab De-escalation in Patients With Crohn’s Disease in Clinical Remission Is Safe and Well-tolerated Jessica R. Allegretti, MD,* ,†, Andrew Canakis, MD, ‡ Emma McClure,* Jenna Marcus,* Beth-Ann Norton, NP,* Matthew J. Hamilton, MD,* ,† Rachel W. Winter, MD,* ,† Punyanganie S. De Silva, MD,* ,† Sonia Friedman, MD,* ,† and Joshua R. Korzenik, MD* ,† From the *Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, Massachusetts, USA † Harvard Medical School, Boston, Massachusetts, USA ‡ Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA Address correspondence to: Jessica R. Allegretti, 850 Boylston Street, Suite 201, Chestnut Hill, MA, 02467, USA. E-mail: jallegretti@bwh. harvard.edu. Key Words: infammatory bowel disease, Crohn’s disease, infiximab, dose de-escalation Introduction Infiximab—a chimeric monoclonal antibody that targets antitumor necrosis factor (TNF) alpha—is an effective bio- logical agent to treat infammatory bowel disease (IBD). 1 Infiximab has demonstrated long-term therapeutic bene- fts in moderate to severe Crohn’s disease (CD) with asso- ciated improvements in quality of life, endoscopic healing, and reduction in steroid use. 2 After induction, infiximab is administered as maintenance therapy to maintain clinical re- mission. Drug concentrations may vary based on disease se- verity, infammation, and other drug clearance mechanisms, 3 and therefore therapeutic drug monitoring (TDM) is often needed to optimize dosing while also monitoring for antidrug antibodies. 4 Infiximab dose escalation in patients with CD is recom- mended in the setting of waning clinical response and low drug trough levels. The need to dose escalate, however, does not necessarily represent a linear deterioration of disease but rather a transient process that requires a subsequent re-evaluation of the dose and frequency of drug administra- tion. Therefore, a dose decrease may be possible once remis- sion and therapeutic drug trough concentrations are achieved. However, there is uncertainty regarding the optimal use of proactive TDM in quiescent IBD as a means towards dose de-escalation. 3 Long-term outcomes have suggested that com- pared with a reactive approach, proactive TDM was associ- ated with better clinical outcomes while also reducing IBD related surgeries, hospitalizations, serious infusion reactions, and antibodies to infiximab (ATI). 5 We hypothesized that for patients with CD in clinical remis- sion infiximab de-escalation would be safe and well tolerated for patients with CD in clinical remission, with or without prior infiximab dose escalation and supr-therapeutic drug troughs (defned as >10 ug/mL). We aimed to determine if patients with CD in clinical remission with supratherapeutic infiximab troughs could be maintained in a sustained clinical remission despite dose de-escalation. Methods This was a prospective pilot trial of CD patients treated with infiximab (at a consistent dose) for at least 1 year at a tertiary IBD referral center in clinical remission. This was defned as a Harvey-Bradshaw Index (HBI) <2 for at least 6 months be- fore enrollment. Subjects had trough levels and ATIs meas- ured at baseline (Prometheus Labs). If the baseline trough was >10 ug/mL with undetectable ATIs, the dose was de-escalated either from 10 or 7.5 mg/kg to 5 mg/kg or from 5 mg/kg to 3 mg/kg. De-escalation only occurs once. Dose intervals were not adjusted. Patients were followed through 3 infusions after de-escalation. Harvey-Bradshaw Index, safety labs, infiximab trough levels, and antibodies were measured at each infusion. Both the patients and assessors were blinded to patient trough levels during evaluations. This protocol was approved by the institution review board at Brigham and Women’s Hospital. All patients signed written consent before study initiation. Results Fifty-two patients with CD in clinical remission on infiximab (all on Remicade, no biosimilars; mean HBI, 0.2) were screened, of which 55.7% (29) were found to have trough level >10 ug/mL at baseline. Ten patients de- clined de-escalation, therefore 19 patients underwent the de-escalation protocol. Among these, mean age was 34.7 ± 13.5, 8 (42.1%) were men, and 100% were white. With regard to disease location, 10 patients had ileocolonic disease, 4 had ileal disease, and 5 had colonic disease. Disease phenotype varied with 10 patients with infamma- tory disease, 4 patients had known structuring disease, and 5 had penetrating disease, of which 3 had perianal disease. Three patients were on concurrent azathioprine. All patients had been on infiximab for >2 years, and for 95% (18), infiximab was their frst biologic. Mean baseline trough was 24.6 ug/mL (range, 10.1–34), and 57.8% (11) were on 8 weeks of dosing. Thirteen patients were de-escalated Downloaded from https://academic.oup.com/ibdjournal/article/27/12/2031/6304577 by guest on 29 October 2023