Summary Background Subcutaneous (SC) vedolizumab is effective in inflammatory bowel diseases (IBD) when administered after induction with two infusions. Aim To assess the effectiveness, safety and pharmacokinetics of a switch from intravenous (IV) to SC maintenance vedolizumab in patients with IBD Methods In this prospective cohort study, patients with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. We studied the time to discontinuation of SC vedolizumab, adverse events (AEs), changes in clinical and biochemical outcomes and vedolizumab concentrations at baseline, and weeks 12 and 24. Results We included 82 patients with Crohn's disease (CD) and 53 with ulcerative colitis (UC). Eleven (13.4%) patients with CD and five (9.4%) with UC discontinued SC vedolizumab after a median of 18 (IQR 8–22) and 6 weeks (IQR 5–10), respectively. Four patients with CD switched to a different drug due to loss of response, nine switched back to IV vedolizumab due to adverse events, and three due to needle fear. Common AEs were injection site reactions (n = 15) and headache (n = 6). Median clinical and biochemical disease activity remained stable after the switch. Median serum vedolizumab concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005). Conclusions Switching from IV to SC vedolizumab maintenance treatment is effective in patients with CD or UC. However, 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.

Cytoimmunological monitoring and quantitative birefringence measurements were used as potential aids in diagnosing acute rejection after heart transplantation instead of histopathological assessment of the endomyocardial biopsy specimen alone. Cytoimmunological Acute rejection is one of the first life threatening complications to occur after heart transplantation. The diagnosis of acute rejection is based primarily on histopathological assessment of the endomyocardial biopsy specimen.' New methods for the diagnosis of acute rejection have now been introduced.2 Noninvasive cytoimmunological monitoring is based on morphological inspection of mononuclear cells combined with phenotype assessment of lymphocyte subpopulations.'" The results of cytoimmunological monitoring, that is, the determination of the number of activated lymphocytes, permits the differentiation between graft acceptance, rejection, and infection (table 1).9 To estimate myocyte contractile function, quantitative birefringence measurements were performed on endomyocardial biopsy specimens. Quantitative birefringence measurements give a quantitative assessment of both the relaxation of the myocytes and their ability to contract after the addition of adenosine triphosphate and calcium. Quantitative birefringence measurements are a reliable monitor for myocardial protection during cardiopulmonary bypass surgery and give an indication of the postoperative condition of the patient.12" In assessing the quality of donor hearts for heart transplantation, quantitative birefringence measurements also provide reliable indices of the graft's viability and its functional state.'5In our heart transplantation programme, cytoimmunological monitoring and quantitative birefringence measurements were introduced to diagnose acute rejection. We compared these methods with the histopathological assessment of the endomyocardial biopsy specimens. The diagnostic usefulness of both assays was expressed in terms of sensitivity, specificity, and predictive value. For cytoimmunological monitoring we determined the best way to express the data-that is, relative proportions v absolute numbers of activated lymphocytes-and the results of the standard immunosuppressive treatment were registered accordingly. Furthermore, a correlation between cytoimmunological results expressed in relative proportions and absolute numbers and the period after transplantation during which cytoimmunological monitoring could best be used was analysed. We measured the quantitative birefringence measurements of biopsy specimens to compare the outcome of histopathological assessment in terms of rejection (Billingham scale') with a functional variable.

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We performed immunological phenotyping of mononuclear cells in tissue sections of 84 endomyocardial biopsies (EMB) showing infiltrates, which were taken from 21 patients after heart transplantation. Data were correlated with histology (grading following Billingham) and cyto-immunologic monitoring (CIM) on blood samples (grading into negative, rejection, or infection, based on leukocyte morphology and T-cell phenotype). Few T lymphocytes were observed in 35 biopsies, and many in 49 biopsies. The semi-quantitative estimate of T cells and CD4/CD8 ratio did not correlate with EMB histology but was related to CIM data. For example, 31 out of 42 cases with a CIM indicative of infection (14 of which showing no rejection on histology) manifested large numbers of T cells. In most cases, the CD4/CD8 ratio was less than 1. The presence of activated cells (bearing interleukin-2 receptors or the CD30 antigen) was not related to EMB histology or to CIM data. The number of T cells (subsets) in EMB was not related to relative or absolute numbers in the blood.

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