P617 Extraintestinal autoimmune phenomena during treatment with vedolizumab

Abstract

Background Extraintestinal side effects in patients receiving Vedolizumab, especially skin and joint reactions, have been described. Underlying mechanisms are unclear. Methods Four patients with extraintestinal symptoms under therapy with Vedolizumab were identified and clinical characteristics were analysed. In one patient with pulmonary symptoms, peripheral blood mononuclear cells (PBMC) were isolated, stained with anti-CD45, anti-CD3, anti-CD29 and anti-49d and assessed by flow cytometry. Results All patients developed extraintestinal symptoms between the first and sixth dose, and the three patients receiving more than three infusions all responded well to the therapy regarding to their intestinal symptoms (decline in Harvey-Bradshaw-Index or modified Mayo-Score). One female patient with ulcerative colitis was diagnosed with thyreoiditis de Quervain, a granulomatous inflammation of the thyroid, based on pathognomic ultrasound features after six doses. The second female patient developed vasculitis of the eye after receiving one dose of Vedolizumab for Crohn's disease (CD). Two male patients, both with Crohn's colitis, presented predominantly with pulmonary symptoms: One suffered from rapidly progressive acute respiratory distress syndrome requiring mechanical ventilation after receiving the fourth infusion; the other presented with dyspnoea and dry cough after the third dose. In both cases, CT-scan showed bilateral infiltrates and hilar lymphadenopathy. Extensive work-up identified no infectious or other specific cause (including repeat cultures and PCR for Mycobacterium tuberculosis complex DNA, Quantiferon assay, urine histoplasmosis antigen, HIV testing, negative autoantibodies; and soluble IL-2 receptor, ACE and CD4/CD8-ratio within normal range). In the latter case, lung tissue obtained during thoracoscopic wedge resection showed multiple characteristic noncaseating epithelioid-granulomas, highly suspicious for pleural and pulmonary manifestation of CD. Analysis of integrin-expression on PBMCs demonstrated a distinct CD29+ (i.e. integrin β 1+) population, an integrin necessary for lymphocyte homing into the lung. After treatment with prednisolone, both the β 1+ cells as well as pulmonary infiltrates vanished, along with complete resolution of clinical symptoms. Likewise, the other patients fully recovered after cessation of Vedolizumab plus administration of steroids, if needed. Conclusion Shifts in integrin-expression triggered by Vedolizumab and consequently altered migrational behaviour of immune cells into other organs than the gut might explain the excellent intestinal response to the drug accompanied by extraintestinal manifestation of the disease in our patients.