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BackgroundTreatments for ulcerative colitis (UC) and Crohn’s disease (CD) include conventional agents and tumour necrosis factor-alpha inhibitors (anti-TNFα). A substantial proportion of patients do not respond, are intolerant to both therapies or these drugs are contraindicated. Vedolizumab, a monoclonal antibody directed against α4β7-integrin that inhibits lymphocyte recruitment to the gastrointestinal tract, provides another therapeutic option.PurposeTo assess the efficacy, safety and economic impact of vedolizumab treatment in UC and CD patients in clinical practice.Material and methodsRetrospective, observational study of patients treated with intravenous vedolizumab from September 2015 to September 2017. Variables: age, sex, diagnosis, previous anti-TNFα therapy, duration, dose variation and analytical parameters: haemoglobin (Hb), C-reactive protein (CRP) and faecal calprotectine (FCP). Clinical response was measured by haemoglobin and CRP variation during induction and maintenance, and FCP reduction. Safety was assessed by reported treatment-emergent adverse events, and economic impact by drug patient-year cost.ResultsForty-one patients, 63% men, mean age 46.6 years (19–76), were included. Indications: 16 patients (39%) UC and 19 (61%) CD. Most of the patients had previously been treated with anti-TNFα therapies (85%), mostly infliximab (88%), while 15% had never had biotherapy. Mean duration was 10.4 (1–30) months. Fourteen patients (34%) required a maintenance dose modification every 4 to 6 weeks instead of every 8 weeks. Mean Hb and CRP levels before vedolizumab administration were 13.3 mg/dl and 18.5 mg/L respectively, improving at the end of the induction in 0.2 mg/dl and 6.4 mg/L, and 0.3 mg/dl and 7.7 mg/L in the maintenance phase. Average FCP reduction was 22.4% from baseline levels to values at the end of the study. With regard to adverse events, 16 patients (39%) reported gastrointestinal events and seven (17%) arthralgias. Treatment was discontinued in two patients due to lack of efficacy. Estimated patient-year cost in our hospital was €18 259 the first year, and €14 202 the following year.ConclusionVedolizumab provides an additional therapy for patients with an inadequate response or were intolerant to anti-TNFα. Effectiveness outcomes in our clinical setting were within the percentages presented in clinical trials either in induction or maintenance, showing a similar safety profile to other biological treatments and to that described in clinical trials.References and/or AcknowledgementsVedolizumab: EPAR-Summary for the public. EMA.No conflict of interest

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Aim and objectives The objective of this study was to perform a preliminary pharmacokinetic (PK) model of adalimumab to evaluate covariates potentially responsible for the PK variability in paediatric patients with IBD. Material and methods A 3 year retrospective multicentre study was performed including children and adolescent (£ 18 years) diagnosed with IBD and treated with adalimumab. Demographic and clinical data were collected, including serum albumin, C reactive protein and faecal calprotectin. Pre-dose serum samples were carried out before administration. Adalimumab concentrations and anti-adalimumab antibodies (AAA) were determined by ELISA. The model was developed in NONMEM V.7.4 by approximating the non-linear mixed effects models. The first order conditional estimation method with interaction (FOCEI) was used for model building. Concentrations below the lower limit of quantification (LLOQ) were set to LLOQ/2. Body weight (WGT) was included in the PK parameters following an allometric relationship. Results Twenty-three paediatric patients (10 women) were included, 3 were diagnosed with ulcerative colitis and 20 with Crohn disease. Median age (range) was 14.0 (5-18) years and weight 55.9 (20.4-80) kg. A total of 75 concentrations (2< LLOQ) were determined, with a medium concentration of 10.72 (0.1-24.7) mg/mL. Median (range) serum albumin level was 4.0 (2.8-5.0) g/dL. Only one patient developed AAA. Population PK model (PopPK): a one compartment with first order absorption and elimination described adequately the serum adalimumab concentration-time data. The absorption rate constant was fixed (Ka=0.008/hour) according to Sharma et al. Among the clinical variables analysed, only albumin was significant on the apparent clearance (CL/F). The final PopPK model in the absence of AAA was as defined as: V/ F=11.30×(WGT/56 kg) and CL/F (L/day)=0.42×(albumin/4 g/ dL)-2.32 × (WGT/56 kg) 0.75. Covariate analysis reduced the interindividual variability associated with CL (IIVCL) from 34.1% to 21.3%. Proportional residual error estimated was 28.4%. Conclusion and relevance Adalimumab PK in paediatric patients with IBD was best described by a one compartment model with first order absorption and elimination. WGT was included in the PK parameters following an allometric relationship. Albumin showed statistically significant differences on adalimumab CL/F, explaining 62.5% of its variability.