The Impact of Vedolizumab and Ustekinumab on Articular Extra-Intestinal Manifestations in Inflammatory Bowel Disease Patients: A Real-Life Multicentre Cohort Study.

BACKGROUND AND AIMS: Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS: An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS: In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS: Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.

Practical Approaches to "Top-Down" Therapies for Crohn's Disease.

Crohn's disease (CD) is a chronic, progressive, and disabling disease that leads in most cases to the development of bowel damage presenting as a fistula, abscess, or stricture. For years, therapy for Crohn's disease has been based on a "step-up" approach, in which anti-TNF agents are administered after the failure of steroids and immunosuppressants. However, recent studies have suggested that early introduction of anti-TNF agents combined with immunosuppressants can modify the natural history of the disease. Patients who could benefit more of this "top-down" strategy would be those at elevated risk of a complicated or severe inflammatory bowel disease or with factors that can predict an aggressive disease course. Therefore, the management of a patient with CD should be personalized, taking into account the patient's specific characteristics and comorbidities, disease activity, site and behavior of the disease, and predictable factors of poor prognosis. A balance between medication and potential adverse effects should be achieved, trying to avoid under or overtreatment, always discussing the different therapeutic options with the patient. The natural history of ulcerative colitis differs from CD and, to date, there is not much scientific evidence on the use of early combined immunosuppression.