Greater endoscopic healing at 1 year might be achieved in people with Crohn’s disease if they are treated with anti–tumor necrosis factor (TNF) drugs than if they are treated with certain other biologics it appears.
In a pooled analysis of data from four different clinical trial programs, which altogether included 344 patients with Crohn’s disease, both an infliximab biosimilar and adalimumab were associated with better endoscopic healing rates of both the ileum and colon than were either vedolizumab or ustekinumab.
The difference disappeared for ileal not colonic involvement, however, if patients had been biologic naive before receiving any of the four drugs that were compared.
“Recent studies have suggested that the ileum and colon differ with regards to their ability to achieve healing in Crohn’s disease,” Neeraj Narula, MD, said in reporting the analysis at the 17th congress of the European Crohn’s and Colitis Organisation.
“Our group has shown that larger ulcers in the ileum and rectum in particular do not heal as well as other areas of the colon when using infliximab therapies,” added Narula, who is an assistant professor of medicine at McMaster University, Hamilton, Ont., and the director of the IBD clinic and staff gastroenterologist at Hamilton Health Sciences.
Whether there are differences in how the ileal and colonic regions heal in response to biologic therapy is not known, which is why Narula and colleagues carried out their analysis.
Pooling Pivotal Trial Program Data
“Our primary aim was to evaluate the efficacy of four approved biologic therapies for Crohn’s disease with regards to their ability to achieve endoscopic healing after continuous use for 1 year,” he noted.
For their analysis, original data from the EXTEND, UNITI, VERSIFY, and infliximab biosimilar CT-P13 clinical trial programs were obtained and pooled.
The extent of mucosal inflammation and thereby healing were determined using a modified version of the Simple Endoscopic Score for Crohn’s disease (SES-CD), which is a measure often used in clinical trials.
At inclusion, patients had to have had an SES-CD score of 3 or more in at least one segment of the ileum or colon and confirmed ulceration. The primary endpoint was endoscopic healing defined as an SES-CD score of 0 after 1 year’s continuous treatment.
Multivariate logistic regression was used, and adjustments were made for potential confounding factors, such as how long people had had Crohn’s disease, the use of steroids, and if there had been prior anti-TNF failure.
Main Results
Overall, 299 patients were in the final analysis; most (n = 141) had been treated with the infliximab biosimilar, with 61 treated with adalimumab, 56 vedolizumab, and 41 ustekinumab.
The highest rate of endoscopic healing at 1 year for ileal involvement was seen with the infliximab biosimilar (36.7% of patients) and the lowest rate with vedolizumab (18.6%), with rates of 30% and 22.7% for adalimumab and ustekinumab, respectively. Only the comparison between the infliximab biosimilar and vedolizumab was statistically significant (P = .038).
As for ileal ulcers, there were fewer seen with both anti-TNF treatments than with either ustekinumab or vedolizumab, at 40.8% for the infliximab biosimilar, 30% for adalimumab, 17.7% for ustekinumab, and 8.7% for vedolizumab. Rates of ileal ulcer absence in biologic-naive patients were a respective 36.7%, 37.5%, 40%, and 21.9%.
In terms of colonic involvement, the lowest rate of endoscopic healing occurred in patients treated with ustekinumab, at 29%, and the highest for adalimumab (62.5%), followed by the infliximab biosimilar (52.4%) and then vedolizumab (31.3%).
Absence of colonic ulcers was similarly low for ustekinumab (29.6%) and higher for the other three groups (64.9%, 70.5%, and 41.2%, respectively). When considering biologic-naive patients, there was a significant difference in the absence of colonic ulcers comparing adalimumab (66.7; P = .004) and the infliximab biosimilar (52.4%; P = .022), but not vedolizumab (37.1%) versus ustekinumab (29.4%).
Lots of Questions and Limitations
Narula’s presentation garnered a lot of questions, with viewers noting that the number of patients was too small or methodologically too flawed to be able to draw any sound conclusions.
“We acknowledge that our study cannot substitute for head-to-head trials of biologics in Crohn’s disease since we cannot account for all confounding variables,” said Narula.
“We did try to account for this limitation by performing some subgroup analyses to account for biologic-naive patients only,” he added, alongside the multivariate analyses.
Also, there might be a difference in the duration of treatment needed before endoscopic healing is seen, as the biologics studied all have a different duration of onset. The dosages used may also be important, and Narula conceded that their analyses were done assuming standard doses, which may not have been optimized.
There were several demographic differences between the infliximab arm and the other treatments. Of note, 76% of patients had been given immunomodulators at the same time, which is known to enhance the effects of infliximab.
Narula pointed out, however, that baseline characteristic were pretty similar in the other three study arms, and adalimumab still showed superiority in the analyses that were performed.
So Are Anti-TNFs the Best Choice?
“Ultimately, we always factor in the therapeutic index of therapy, trying to weigh benefit versus risk,” Narula said in answering a question from the chair of the session on the risks associated with anti-TNFs.
“We didn’t compare risk within this clinical trial, but certainly risk can be compared, and there’s things like number needed to treat versus number needed to harm to ultimately come at a best answer for the patient,” he added.
Narula disclosed receiving grants from Takeda and Pfizer; personal fees from AbbVie, Janssen, Takeda, Pfizer, Merck, Amgen, and Sandoz; and nonfinancial support from AbbVie, Janssen, Takeda, Pfizer, Ferring, and Lupin. The data used in the analysis were obtained through YODA Project #2021-4778 which has an agreement with Janssen Research & Developmen and via Vivli, which has access to data from AbbVie and Takeda. Data were also obtained with permission from Celltrion.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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