IBD Shorts: High TNF levels, Biologics in Pregnancy, & Ileocolic Resection Outcomes in Pediatrics

M Zvuloni et al. JPGN 2021; 73: 717-721. Open Access PDF: High anti-TNFa Concentrations Are Not Associated With More Adverse Events in Pediatric Inflammatory
Bowel Disease

Key findings (retrospective study):

  • Higher trough concentrations (TCs) (>10 mcg/mL) of anti-TNFa were not associated with higher rate of anti-TNFa-related adverse events in 135 patients & >1500 TC measurements
  • Out of the 30 patients who presented with elevated transaminases, 27 (90%) patients had normalized transaminases values by the end of the follow-up
  • Adverse events were noted in 68 of 135 patients (see below)

OH Nielsen et al. Clin Gastroenterol Hepatol 2022; 20: 74-87. Open Access: Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis

Forty-eight studies were included in the meta-analysis comprising 6963 patients. Key findings:

  • Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% for early pregnancy loss, 9% for preterm birth, 0% for stillbirth, 8% for low birth weight, and 1% for congenital malformations.
  • These rates are comparable with those published in the general population.
  • Importantly, studies with newer biologics (eg. vedolizumab, ustekinumab) had small sample sizes. In addition, ongoing prospective multicenter registries are ongoing.

EA Spencer et al. JPGN 2021; 73: 710-716. Open Access PDF: Outcomes of Primary Ileocolic Resection for Pediatric Crohn Disease in the Biologic Era

Key findings (n=78, retrospective study, 2/3rds received biologic postoperative prophylactic therapy):

  • Endoscopic recurrence was 46% at 2 years (median time to recurrence: 10 months).
  • Histologic recurrence was present in 44% in endoscopic remission
  • At diagnosis and surgery, over a quarter met the criteria for growth failure.. Following surgery, height, weight and BMI z scores improved significantly both at 1 year and last followup

IBD Update -December 2020

DHW Little et al. Am J Gastroenterol 2020;115:1768–1774. Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review (Thanks to Ben Gold for this reference)

In this systematic review, a total of 995 adult patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial.

Key findings:

  • Biologic dose de-escalation was associated with relapse rates as high as 50% at 1 year. Overall, clinical relapse occurred in 0%–54% of patients who dose de-escalated biologic therapy (17 studies).
  • Lower rates of relapse (10%–25%) were reported in studies involving patients with endoscopic and/or histologic remission
  • These results are in agreement with a previous meta-analysis, which found a 1-year risk of relapse after discontinuation of anti-TNF therapy of 36% in CD and 28% in UC ( Gisbert JP, et al.. Am J Gastroenterol 2016;111:632–47).

My take: This study shows that dose de-escalation of biologic therapy in IBD
seems to be associated with high rates of clinical relapse

C Chapuis-Biron et al. Am J Gastroenterol 2020;115:1812–1820. Ustekinumab for Perianal Crohn’s Disease: The BioLAP Multicenter Study From the GETAID (Thanks to Ben Gold for this reference too)

In this national multicenter retrospective cohort study in 207 adult patients with either active or inactive perianal Crohn’s disease (pCD) who received ustekinumab (2017-2018). The majority had received multiple biologics (~85% had at least 2 anti-TNF agents, 28% had received vedolizumab) and prior anal surgeries (mean 2.8).

Methods: Success of ustekinumab was defined by (i) clinical success at 6 months of treatment assessed by the physicians’ judgment, with (ii) no need for dedicated medical treatment for perianal lesions (antibiotics and/or topics) nor (iii) unscheduled surgical treatment. For perianal disease evaluation, clinical success was defined in the study protocol, by the absence of draining pus for fistulas, and no anal ulcers

Key findings:

  •  In patients with active pCD, success was reached in 57/148 (38.5%) patients.
  • Among patients with setons at initiation, 29/88 (33%) had a successful removal.
  • In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively.
  • The absence of ustekinumab optimization was associated with upper odds of success (OR 2.74). “We can suppose in our present study that optimization of treatment was needed in severe refractory patients with no or insufficient response to ustekinumab. Thus, in these nonresponders, success was not achieved despite optimization.”

My take (partly borrowed from authors): “This large multicenter dedicated study adds
substantial evidence to the growing literature on ustekinumab effectiveness in refractory CD.” For pCD, optimization of ustekinumab has a low likelihood of improving response.

Related blog posts -De-escalation:

Related blog posts -Ustekinumab/Crohn’s Disease:

How Do Home Infusions Stack Up?

One of the advantages of infusions in the office (or hospital) compared to home infusions and home injections is close communication by those giving the infusion with the physician.  In addition, with each infusion, in these settings offers an opportunity to review the patient’s progress and adjust the patients orders.  A recent study (Fenster M, et al. Clin Gastroenterol Hepatol. 2019;10.1016/cgh.2019.03.030.) indicates that these advantages may make infusions more successful than infusions given at home.

A summary is offered by Healio Gastroenterology: Home biologic infusions in IBD suffer from lack of monitoring

Researchers conducted a matched retrospective cohort study of patients treated with infliximab or vedolizumab with home infusion (n = 69) compared with hospital infusion at a large, tertiary care IBD center.  The primary endpoint was a composite of adverse outcomes, including stopping biologic therapy, IBD-related emergency department visit or IBD-related hospitalization.

  • “Patients on home infusion were more likely to experience adverse outcomes compared with control patients (43.5% vs. 21.7%; P = .006), and they also had a shorter time to adverse outcomes than patients who got hospital infusions.”
  • “Patients with home infusions trended toward stopping therapy within 1 year (20.3% vs. 8.7%; P = .053) and stopping therapy within the complete follow-up window (27.5% vs. 15.9%; P = .099) compared with controls.”
  • Patients with home infusions had “more emergency department visits (30.4% vs. 7.2%, P < .001), they did not have significantly more hospitalizations (17.4% vs. 11.6%).”

The authors noted that the “increase in adverse events might have been related to a reduced level of monitoring observed in home infusion patients. In the year following home infusion initiation or matching, patients who persisted on home infusions had significantly fewer IBD clinic visits (1.23 vs. 1.75; P = .018) compared with controls.”

My take (borrowed from a previous post): In my experience, office-based infusions can be provided safely and in a cost-effective manner.  While the convenience and potential cost-savings of home-based infusion are desirable, before implementing broadly, issues regarding communication, safety protocols, and documentation to allow modifications in therapy need to be proactively addressed. These issues could affect a patient’s long-term response to biologic therapy.

Related blog posts:


Increasing Cost/Use of Biologic Therapies for Inflammatory Bowel Disease

As noted in a previous blog post (Changes in the Use of IBD Biologic Therapy), there has been an increased use of biologic therapy early in the course of patient’s with inflammatory bowel disease (IBD). Another retrospective study (H Yu et al AP&T 2018; 47: 364-70 -thanks to Ben Gold for this reference) examines the market share and costs of biologic therapy for IBD using the Truven Marketscan Commercial Claims and Encounters database (2007-2015).  This database consists of out-patient and in-patient pharmaceutical claims of approximately 40-50 million privately insured patients each year from patients from all 50 states (U.S.).

Key findings:

  • Among 415,405 patients with IBD (188,842 with Crohn’s, 195,183 with ulcerative colitis, 31,380 with indeterminate IBD), the proportion using biologics increased over the 9-year period (2007-2015); overall, the market share increase was from 7.1% (2007) to 20.5% (2015).
  • There were 28,797 pediatric patients with IBD (17,296 with Crohn’s, 9368 with ulcerative colitis, and 2133 with indeterminate colitis). The overall market share in pediatric patients was the highest, increasing from 19.1% to 45.9%.
  • For all patients with Crohn’s disease (CD) the proportion receiving biologic therapy increased from 21.8% to 43.8%.  For patients with ulcerative colitis (UC), the proportion increased from 5.1% to 16.2%.
  • Per-member per-year (PMPY) costs increased. “The average biologic-taking patient accounted for $25,275 PMPY in 2007 and $36,051 PMPY in 2015.”  This was similar in the pediatric population, going from $23,616 PMPY in 2007 to $41,109 PMPY in 2015.
  • The share of costs of medicines: the costs of biologics as a share of the total increased from 72.9% in 2007 to 85.7% in 2015. 95% of the pharmacy costs in children with IBD are attributed to biologics.

My take: This trend of increasing use of biologics and their associated costs is going to continue due to their effectiveness. While there are direct costs related to these medications, the net cost is unclear as they can prevent hospitalizations and surgeries. In addition, by helping to spare corticosteroids and increasing response rates, biologic therapies improve quality of life, minimize opportunity loss, and optimize long-term health outcomes.

Bright Angel Trail, Grand Canyon