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Background Vedolizumab (VDZ) is a gut-selective, anti-lymphocyte trafficking drug inhibiting α4β7-integrin approved for treatment of moderately to severely Crohn's disease (CD) and ulcerative colitis (UC). Methods This was a retrospective cohort study based on review of patients charts from sites in Spain and Portugal. The primary objectives are to compare real-world clinical effectiveness and treatment patterns data on the use VDZ vs. anti-TNFα in UC patients, either as the first biologic or after failure to a single anti-TNFα. Inverse probability treatment weights (IPTW) were used to balance both cohorts on the baseline demographic and clinical characteristics. Results 199 UC patients were included with a median follow-up of 24 months. One hundred and two (51%) patients started treatment with VDZ, and 44% of them were bio-naïve. In the anti-TNFα cohort, 77% of patients were bio-naïve. Clinical response rates were similar in both groups at week 14, 81% in VDZ cohort vs. 80% in anti-TNFα cohort (p=0.91) and at week 52, 76% in VDZ treated patients vs. 73% anti-TNFα treated patients (p=0.72). Clinical remission rates at week 14 were 52% for VDZ group vs. 55% in anti-TNFα group (p=0.76). At week 52, clinical remission rates were 57% for VDZ vs. 62% for anti-TNFα (p=0.49). Treatment intensification was needed in 44% of VDZ treated patients vs. 40% in the anti-TNFα group (p=0.58), and median time (months) to first treatment intensification was 6.4 in the VDZ group vs 5.8 in the anti-TNFα group (p=0.96). Discontinuation rates during the follow up were 40% for VDZ treated patients vs. 50% for anti-TNFα treated patients (p=0.17) (Fig.1). Among patients with endoscopic assessments available at week 52, endoscopic remission rates were 36% in VDZ cohort (n=9/25) vs. 36% in anti-TNFα cohort (n=9/25) (p=0.95). And among those patients with biochemical assessment available, biochemical remission (fecal calprotectin Conclusion Overall, these findings show similar effectiveness with VDZ and anti-TNFα when used as the first or second biologic for UC patients after 1 year, but a safety advantage in favor of VDZ, supporting a favorable benefit-risk ratio in favor of VDZ.

Background Vedolizumab (VDZ) is a gut-selective, anti- lymphocyte trafficking drug inhibiting α4β7-integrin approved for treatment of moderately to severely Crohn's disease (CD) and ulcerative colitis (UC). Methods Medical charts from CD patients were retrospectively reviewed in sites from Spain and Portugal. The primary objectives are to compare real-world clinical effectiveness and treatment patterns data on the use VDZ vs. anti-TNFα in CD patients, either as the first biologic or after failure to a single anti-TNFα. Inverse probability of treatment weights (IPTW) were used to balance both study cohorts for the baseline demographic and clinical patient characteristics. Results 210 CD patients were included with a median follow-up of 26.0 months. Eighty-three (40%) patients started treatment with VDZ, being 57% of them bio-naïve. In the anti-TNFα cohort, 76% of patients were bio-naïve. Clinical response rates at week 14 were higher for anti-TNFα group (88%) vs. VDZ group (68%) (p=0.007). However, at week 52, clinical response rates were comparable with 75% in the VDZ group and 70% in the anti-TNFα group (p=0.48). Clinical remission rates at week 14 were higher for anti-TNFα group (79%) vs. VDZ group (56%) (p=0.005). However, at week 52, clinical remission rates were comparable among VDZ and anti-TNFα cohorts, 51% vs. 67%, respectively (p=0.07). The rate of treatment intensification was 31% in VDZ vs. 42% in the anti-TNFα group (p=0.13). Median time (months) to first treatment intensification was 8.8 in the VDZ group vs. 6.3 in the anti-TNFα group (p=0.83). The overall discontinuation rates were 39% with VDZ vs 49% with anti-TNFα (p=0.16) (Fig.1). Among patients with endoscopic assessments available, endoscopic remission occurred in 47% of patients in the VDZ group (n=7/15), and in 42% of patients in the anti-TNFα arm (n=10/24) (p=0.86) at week 52. And among those patients with biochemical assessment available, biochemical remission (CRP Conclusion This real-world study supports the long-term use of VDZ as the first or second biologic for CD patients, showing similar effectiveness than anti-TNFα after 1 year, but better safety outcomes.

Limited data exist regarding sex bias and viral decay in children with HIV. We investigated the sex differences in viral decay in 25 perinatally HIV-infected children. Females presented faster phase I viral decay regardless of their age at antiretroviral therapy (ART) initiation, baseline CD4 percentages, or baseline RNA levels. Also, for each month elapsed under ART, females had faster viral decay than males.

Background and Aims Mycophenolic acid (MPA) is one of the most used immunosuppressive drugs. It is teratogenic in women with a typical embryopathy profile. Regarding its effect on the children of male kidney transplant recipients, although clinical evidence does not indicate a greater risk of malformations, the European Medicines Agency and the Spanish Agency for Medicines and Health Products introduced in 2015 the recommendation to use contraceptive methods because of their genotoxic potential. For this reason, we propose to study the results of the Spanish Kidney Transplant Centers. Method Multicenter retrospective observational study in which 15 Kidney Transplant Centers have participated. Of 3934 men ≤ 60 years old that received a kidney transplant between 2000 and 2015, 3023 were contacted, and 159 men who fathered at least one post-transplant pregnancy (total 252 fetuses) were included. We compared the incidence of abortions and live births with malformations among those who received MPA at the time of conception vs. those who did not. Results In the 252 fetuses (characteristics in table 1) there was an exitus and no differences were detected in the incidence of abortions between the group exposed to MPA (n = 230) and the unexposed group (n = 22), 11.3% vs 18.2%, p = 0.31. Among the 221 live-born fetuses, no differences were found in congenital malformations between the group exposed to MPA (n = 203) and the unexposed (n = 18) 4.9% vs. 16.7%, p = 0.07. Among the malformations described, the typical embryopathy profile of the MPA was not found. Conclusion According to the data of this retrospective national multicenter study, the use of MPA in male kidney transplant recipients does not cause a greater number of abortions or congenital malformations. For these reasons, and given the evidence also published by other groups, it seems necessary to reevaluate the recommendation given on contraception in men treated with MPA.

Background and Aims Extracorporeal photopheresis (ECP) is an apheresis modality that in the field of solid organ transplantation (SOT) has an indication in the treatment or prophylaxis of pulmonary, cardiac or hepatic graft rejection. The usefulness of ECP in renal transplantation (RTx) remains contradictory because of the few studies that evaluate the effectiveness and safety of this technique. Method Case series study of kidney transplant patients with histological diagnosis of rejection who have been treated with ECP during the 2013-2018 period (n = 8 patients). The technical characteristics of the ECP sessions (n = 89) were studied, including tolerance and complications in each of them. Results Demographic and clinical characteristics are shown in Table 1. The indication of FEC was the contraindication to conventional treatment (n = 4), mainly due to concomitant infection (50%), or refractoriness (n = 4) to the treatment prescribed in each case and it is specified in Table 1. The initial schedule was 2 consecutive weekly sessions for 5 weeks, with additional sessions depending on the evolution at the end of the first batch. The scheduled sessions could be completed in most patients (n = 5). The 3 reasons for discontinuation were the lack of response to treatment, hospital admission and thrombosis of the arteriovenous fistula (AVF). The improvement of graft function in terms of creatinine reduction at the end of therapy occurred among patients presenting with acute cellular rejection (ACR) (n = 4) and it remained 3 months after the end of the treatment. The only late ACR (> 3 months post-transplant) could not complete the initial programming. No graft with humoral component showed improvement in renal function. Graft loss and dialysis restart occurred in a patient with chronic active antibody-mediated rejection (cAMR). The other patient with cAMR is in a pre-dialysis situation. A total of 89 procedures were studied, all performed with the THERAKOS® CELLEX® Photopheresis System, with the administration of the methoxsalen solution (UVADEX®) and photoactivation with ultraviolet A light. Vascular access per session was the AVF (76% ) or the central vascular catheter (CVC) (24%), under no circumstances was peripheral access used. Each procedure lasted on average 112.72 +/- 13.85 minutes (range, 86-145). The volume of treatment (“buffy coat”) was 189.11 +/- 28.67 mL per session, and the total volume of fluids administered (NaCl and anticoagulation) was 559.40 +/- 41.17 mL. The complications observed during the sessions were fever (n = 2), thrombosis of the AVF (n = 1), coagulation of the extracorporeal system (n = 1) and anemization (n = 1). Interprocedure there was a case of urinary infection that conditioned hospital admission and discontinuation of therapy. One patient died of cardiovascular cause with a functioning graft 4 years after therapy. Conclusion The utility of the ECP seems to be in cases of cell rejection, probably related to the triggering of an immunomodulatory response of lymphocytes. It can be considered a well-tolerated and safe treatment. Special care should be taken with patients who require water restriction (infusion of 560 mL on average per session). We need more studies with a greater number of patients and a control group to be able to confirm the effectiveness and safety of PEC in RTx and to be considered a useful therapeutic tool as in other SOT.

Objective. The objectives of the study were to determine the absolute bioavailability of fentanyl from fentanyl buccal soluble film, estimate the percentage of a fentanyl dose absorbed through the buccal mucosa, and compare the bioavailability of equivalent doses administered either as single or multiple dose units. Design. Open-label, randomized, four-period, Latin-square crossover pharmacokinetic study. Setting. Inpatient phase 1 unit. Patients. Twelve healthy volunteers. Interventions. Injectable fentanyl citrate (200 µg) administered by intravenous infusion, injectable fentanyl citrate (800 µg/16 mL) administered orally, and fentanyl buccal soluble film (800 µg) administered as a single film and as four separate 200 µg films simultaneously. Outcome Measures. Plasma concentrations after fentanyl dosing; pharmacokinetic parameters. Results. The two buccal film treatments were bioequivalent and both had an absolute bioavailability of 71%. The percentage of an administered dose absorbed through the buccal mucosa was calculated to be 51%. Conclusions. Fentanyl buccal soluble film effectively delivers a high percentage of the administered fentanyl dose and nearly identical plasma profiles are obtained when equivalent doses are delivered by single or multiple dosage units.