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New ACG Crohn’s guideline reflects ‘cross-fertilization’ of knowledge
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The American College of Gastroenterology released an updated clinical guideline on the management of adults with Crohn’s disease, informed by the most recent medical research and expert opinion.
According to guideline co-author Gary R. Lichtenstein, MD, FACG, of the Perelman School of Medicine at University of Pennsylvania in Philadelphia, this new guideline represents a timely update for practitioners, as much has evolved in the management of inflammatory bowel disease since the last published practice guideline on Crohn’s disease.
One major change is the move from the “step-up” approach to choosing an appropriate therapy based on a patient’s prognosis, he said.
“In the past, we used to treat based on symptoms and we didn’t really prognosticate, whereas now we can look at patients and determine whether they have a good or bad prognosis and use appropriately aggressive therapy at the outset if needed,” he told Healio Gastroenterology and Liver Disease. “So rather than use what was termed the ‘step-up’ approach like we have in the past, now if a patient has adequately significant disease, they can go right to a biologic.”
Additionally, physicians have now incorporated the “treat-to-target” approach when treating patients with Crohn’s disease.
“This involves setting targets for subjective and objective points of remission in an effort to optimize care, and in doing so we get baseline assessment, choose a therapy, and then we try to optimize the therapy,” he said.
This treatment approach has been used in other diseases like diabetes, hypertension and rheumatoid arthritis, he noted. The SHARP score, for example, has been used to define joint damage in rheumatoid arthritis, and similarly, the LEMANN score, while not widely used in clinical practice, can be used to help quantify the damage to the bowel in a similar effort.
“We also look at targets such as mucosal healing, and we adjust the agents based on different parameters, like the biomarkers calprotectin and CRP,” he said. “By healing mucosa, we now recognize there are positive outcomes for patients including less surgery, less hospitalization, and better quality of life.”
Finally, therapeutic drug monitoring has become better established in the management of patients with Crohn’s disease, he said.
“Therapeutic drug monitoring is something we strongly advocate,” he said. “It’s been better established for patients who have a secondary loss of response ... and it has enabled us to better treat our patients and really understand the pharmacokinetics as it relates to care. It’s also been shown to be a cost-effective maneuver. Our goal is to give patients the best treatments available for their disease state, and to modify them accordingly to their response or lack thereof — a precision medicine approach.”
Key diagnostic updates
The updated guideline includes 60 recommendations based on GRADE criteria, and 53 summary statements.
According to Lichtenstein, the updated diagnostic recommendations are especially important.
“When it comes to diagnosis, we now advocate use of biomarkers such as fecal calprotectin in helping with the differential diagnosis in patients for whom it is unclear whether they have IBD or irritable bowel syndrome,” he said.
Additionally, the guidelines recommend against the universal use of chromoendoscopy for IBD colorectal neoplasia surveillance.
“We believe HD white light endoscopy is adequate, with the caveat that we suggest that those with prior dysplasia or primary sclerosing cholangitis might be considered for chromoendoscopy, but these two subsets are not well studied,” he said.
Further, the guideline recommends that endoscopists consider foregoing random surveillance biopsies if they are adequately trained and comfortable performing chromoendoscopy.
Treatment updates
A key update in the treatment of Crohn’s disease is based on recent data showing that oral mesalamine is not effective for induction of remission.
“Oral mesalamine has not consistently been shown to be effective compared with placebo for induction of remission, and certainly there is not significant data to show mucosal healing in patients with Crohn’s disease, so we suggest this not be used to treat patients with active Crohn’s,” Lichtenstein said. “This is something that’s currently used very widely.”
Another update, which is quite unique, he noted, is that patients with a low risk of progression may manage their disease with non-specific medications, diet and careful observation.
“For those who have a low risk of progression, treatment of active symptoms with non-specific medications like antidiarrheals, as well as dietary manipulation along with just careful observation for inadequate symptom relief, worsening inflammation, or disease progression is totally acceptable,” he said. “In other words, no anti-Crohn’s directive medical therapy for those with low risk of progression, but re-evaluation is something that needs to be done over time because they may then have a change in the trajectory of their disease course. This has never been recommended in the past, although it’s been practiced in that fashion and certainly there’s been supportive data to advocate for it.”
Another change from the prior guideline is the recommendation against the use of azathioprine for achieving short-term remission, Lichtenstein noted.
“Azathioprine is really not more effective than placebo to induce short-term symptomatic remission and shouldn’t be used in that fashion, and we have at least two studies that support this,” he said. “However, thiopurines are effective and should be considered for their steroid sparing effect in Crohn’s, and that’s where they may be beneficial.”
An important use of antimetabolites, he added, includes combining them with biologics in order to help increase biologic drug levels.
“This has been shown mainly with infliximab with either methotrexate or with azathioprine or 6MP,” he said. “They’ve been shown to boost the levels, and we perceive that the drug levels are one of the strongest drivers of benefit. In other words, patients with higher drug levels do better in aggregate than those with low drug levels.”
The guideline also includes an important group of recommendations concerning biologic therapy. Of note, patients should no longer have to fail one biologic to get to another, Lichtenstein said.
“In other words, one does not have to start with anti-TNF as the primary agent; it is appropriate to initiate therapy with an anti-integrin (vedolizumab) or an anti-interleukin 12/23 agent (ustekinumab). In general, we choose an appropriate biologic class based on their disease activity and their disease course,” he said. “We divide up disease course and disease activity in the guidelines, and that’s a major change from the past because we really never considered the prognosis of the patient when assessing Crohn’s disease activity.”
The management of postoperative Crohn’s disease has also evolved, and the guidelines thus include several recommendations in this area, he said.
“Smoking cessation is very important because this is beneficial for many different reasons,” he said. “Additionally, mesalamine has limited benefit, but certain antibiotics — imidazole derivatives such as metronidazole and ornidazole — do help to prevent recurrence. Similarly, thiopurines have been shown to prevent clinical and endoscopic recurrence but they’re not effective at preventing severe endoscopic recurrence.”
Finally, high risk patients on anti-TNF therapy should be started within 4 weeks of surgery to prevent post-op Crohn’s disease, he said.
“This is based on the best evidence we have to date,” he said. “Also, we note that although there’s lack of data for postop Crohn’s disease, anti TNF therapy should be considered in combination with an immunodulator post-operatively to decrease immunogenicity and to decrease loss of response. There’s not a lot of data for that particular statement but it makes intuitive sense based on other IBD studies.”
Lichtenstein concluded that the guideline does carry a substantial amount of change and noted this has been made possible by learning from clinical studies and clinical practice in other specialties.
“There’s a ‘cross fertilization’ that’s really enhanced our knowledge and enabled us to assimilate these guidelines,” he said. “They should help the practitioner make educated and evidence-based treatment decisions with the patient as the central focus.” – by Adam Leitenberger
Disclosures: Lichtenstein reports financial relationships with AbbVie, Actavis, Alaven, CellCeutrix, Celgene, Ferring, Gilead, Hospira, Janssen, Orthobiotech, Ironwood, Luitpold/American Regent, Merck, Pfizer, Prometheus Laboratories, Romark, Salix Pharmaceuticals/Valeant, Santarus/Receptos/Celgene, Shire Pharmaceuticals, Takeda, UCB. Please see the full guideline for a list of all other co-authors’ relevant financial disclosures.
Editor's Note: This article was updated on March 28 with clarifications from Lichtenstein.
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