Real-life experiences of switching from intravenous to subcutaneous vedolizumab maintenance therapy in patients with inflammatory bowel disease.

BACKGROUND: A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking. OBJECTIVE: The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations. METHODS: We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres. RESULTS: Altogether, 103 patients (26 Crohn's disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients (P = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml). CONCLUSION: Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study.

BACKGROUND AND AIMS: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. MATERIALS AND METHODS: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. RESULTS: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). CONCLUSION: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Benefit of measuring vedolizumab concentrations in inflammatory bowel disease patients in a real-world setting.

OBJECTIVES: We set out to determine the reasons for serum vedolizumab (VDZ) trough concentration (TC) measurements in inflammatory bowel disease (IBD) patients and to evaluate treatment modifications after therapeutic drug measurement (TDM). We also evaluated the effect of increased dosing on patients' response to VDZ therapy. METHODS: We performed a retrospective cohort study of IBD patients who received VDZ therapy at Helsinki University Hospital and whose VDZ levels were measured between June 2014 and December 2018. RESULTS: Altogether, 90 patients (32 Crohn's disease and 58 ulcerative colitis) and 141 VDZ TC measurements were included. 24.1% of measurements took place during induction and 75.9% during the maintenance phase. During induction, 64.7% reached the target TC >20µg/ml. During maintenance therapy, 82.2% of VDZ TCs were within or exceeded the suggested target range of 5-15µg/ml. Reasons for TDM were: secondary nonresponse (44.0%), assessment of adequate VDZ TC (25.5%), primary nonresponse (12.8%), adverse events (6.4%), and other (11.3%). No treatment changes occurred after 60.3% of VDZ measurements. Increased dose frequency was used after 25.5% of VDZ measurements and 33.3% of these patients experienced improvement. Altogether, 31 (34.4%) patients discontinued the therapy due to inadequate treatment response. No anti-vedolizumab antibodies were detected. CONCLUSIONS: During the maintenance of VDZ therapy, the majority of VDZ TCs were within the suggested range. Measurement of VDZ TC did not lead to any treatment changes in two-thirds of patients. Dose optimization occurred in a quarter of patients and a third of them benefited from it.

Impact of anti-TNF-alpha therapy on colectomy rate and indications for colectomy in ulcerative colitis: comparison of two patient cohorts from 2005 to 2007 and from 2014 to 2016.

Objectives: The aim of this study is to assess the impact of biological therapy on the colectomy rate and indications for colectomy in ulcerative colitis (UC) at Helsinki University Hospital (HUH) catchment area in Finland. Methods: This study was conducted retrospectively by comparing two cohorts of UC and indeterminate colitis patients that underwent colectomy in a single centre in HUH during the years 2005-2007 and 2014-2016. All patient data were collected from hospital patient records. Results: In 2005-2007 and 2014-2016, respectively, 2.3 and 18.8% of patients had received biological therapy and more specifically 2.3 and 10.5% infliximab within 3 months prior to colectomy. Colectomy rates were 8.6 (7.2-10.2) and 5.1 (4.3-6.1)/1.000 patient-years (p < .001). During 2005-2007 and 2014-2016, the indications for colectomy were: refractory disease 79.1 and 79.7%, dysplasia 16.3 and 12.8%, cancer 2.3 and 3.0% and other reasons 2.3 and 4.5%, respectively. Emergency colectomy covered 8.5 and 9.8% of the operations. Conclusions: In addition to the markedly increased use of biological therapy during the time preceding colectomy, we noticed a significantly decreased rate of surgery but no changes in the indications for colectomy. Biological therapy seems to have had a favourable effect on the colectomy rate. Even so, the main indication for surgery is still a refractory disease, suggesting urgent need for better treatment options.