Vedolizumab‐associated pulmonary manifestations in children with ulcerative colitis

Abstract

Vedolizumab (VDZ) is a humanized monoclonal antibody and an antiintegrin molecule which interferes with lymphocytes trafficking in the inflamed gastrointestinal tract, therefore reducing immune cell infiltration and local inflammation. 1 In particular, VDZ is characterized by a gut selectivity thanks to its interaction with a4b7-integrin, which is expressed specifically by a subset of gastrointestinalhoming T lymphocytes. Such a blockade prevents the binding of a4b7-integrin-positive leukocytes to the mucosal addressing cell adhesion molecule-1 (Mad-CAM-1) and their translocation from the blood into the inflamed gastrointestinal submucosa. 1 Integrin antagonists represent a relatively new class of therapy and an attractive option for the treatment of inflammatory bowel disease (IBD) as they target different inflammatory pathways in patients who are refractory or intolerant to tumour necrosis factor (TNF)α inhibitors.In addition, they are reported to show reduced systemic side-effects due to gastrointestinal selectivity. 1 Pivotal phase-3, double-blind, placebo-controlled studies, i.e.GEMINI studies 1 and 2, have shown VDZ to be effective in inducing and maintaining clinical remission in adult ulcerative colitis (UC) and Crohn's disease (CD), respectively. 2,3 Based on these results, VDZ has been approved for the treatment of moderate-to-severe CD and UC in patients of 18 years and older who are refractory or intolerant to either conventional treatments or anti-TNFα agents. [3][4][5] The effectiveness and safety of VDZ has been assessed in several real-world studies, displaying promising results both in adult and paediatric settings. 1 Moreover, beyond clinical remission, VDZ has been shown to induce endoscopic and histologic healing, with higher rates in UC than CD. 4,6 Overall rates of adverse events, serious adverse effects, and serious infections were not different between patients treated with placebo and those who received VDZ. 5,7 AEs reported from pooled data of clinical trials were approximately 30.6%, and mostly minor, including myalgia and arthralgia, followed by nasopharyngitis, infection, and skin infections. 8 The exposure-adjusted incidence rates of infections

Pathophysiological Concepts and Management of Pulmonary Manifestation of Pediatric Inflammatory Bowel Disease

“…These cells consequently remain in the pulmonary parenchyma, leading finally to tissue damage [169]. Recently, a case of a child experiencing VED-associated pulmonary disease was published, probably based on an integrin shift leading to proliferation of CD29 + lymphocytes (β1-integrin), which amplifies lymphocyte homing to the lung [170]. Mitchel et al reported the case of a child with non-infectious bilateral pneumonia after the initiation of immunosuppressive therapy with UST [171].…”

Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease – Data from the multicenter CEDATA-GPGE registry study

“…More serious adverse events have been reported in single case studies. In two patients with UC, Pott’s puffy tumor ( 26 ) or persistent and productive cough ( 27 ) was described in response to treatment with vedolizumab.…”