IOIBD Issues EXTRA Consensus on Assessing EIMs in Trials

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has issued an expert consensus document on how to assess extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) in clinical trials.

The authors observed in Lancet Gastroenterology & Hepatology that “the documentation of extraintestinal manifestations and of the effect of drugs on their treatment is still not standardized in IBD clinical trials. This lack of standardization leads to difficulty in interpreting data from clinical trials, because most information is of poor quality and is gathered from post-hoc analyses.”

They continued, “The objective of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative, from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), was to achieve an international expert consensus to provide clear recommendations for homogenizing and standardizing the assessment of extraintestinal manifestations in IBD clinical trials.”

In clinical practice, the authors noted, “extraintestinal manifestations are challenging conditions that require a multidisciplinary approach and specific tools for diagnostic investigations and follow-up to enable the best approach to care.”

A panel of 41 attendees, including gastroenterologists and referral specialists, met in 2021 to begin the process of creating this guideline. The participants identified endpoints that are easy to establish for assessing the response of EIMs to treatment without specialist involvement, agreeing that uveitis, peripheral spondyloarthritis, and arthralgia required the involvement of specialists to create endpoint measurements.

The EXTRA consensus has now proposed guidelines “on how to thoroughly evaluate extraintestinal manifestations within IBD trials and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.”

The panel noted that EIMs comprise a broad range of conditions, from arthralgias and both axial and peripheral spondyloarthritis to ocular conditions such as uveitis and scleritis, cutaneous manifestations such as pyoderma gangrenosum, erythema nodosum, and Sweet syndrome, and hepatopancreatobiliary conditions including primary sclerosing cholangitis, hepatitis, and pancreatitis. EIMs may also be associated with other immune-mediated inflammatory diseases, such as psoriasis, psoriatic arthritis, and hidradenitis suppurativa. 

“Depending on definition, the prevalence of extraintestinal manifestations ranges from 19% to 40% in patients with IBD,” the authors wrote, and “have a substantial effect on patients' quality of life.”

In the systematic literature review conducted for this initiative, the panel found, “Most papers stated that the management of extraintestinal manifestations requires collaboration between different referral specialists. Dedicated specialists were involved in 60–100% of studies depending on the extraintestinal manifestation. Our review highlighted that the diagnostic approach for extraintestinal manifestations, the response to treatment, and the timing of assessment are not standardized in IBD trials. These findings show the need for a consensus to homogenize practices.”

To provide that consistency, the EXTRA IOIBD consensus established 21 recommendations for assessing EIMs in IBD clinical trials, providing a framework to ensure appropriate proper diagnosis and evaluation at baseline and standard measures for assessment of outcomes.  

“Adherence to these recommendations should homogenize the assessment of extraintestinal manifestations in IBD trials. Referral specialists will have a crucial role in future studies to ensure the best approach for the diagnosis and the follow-up of extraintestinal manifestations. These recommendations should be adopted in upcoming clinical trials to enable the field to move forward.”

—Rebecca Mashaw

Reference:
Guillo L, Abreu M, Panaccione R, et al. Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases. Lancet Gastro & Hep. Published online first January 17, 2022. DOI:https://doi.org/10.1016/S2468-1253(21)00297-1