Tacrolimus Exerts Only a Transient Effectiveness in Refractory Pediatric Crohn Disease: A Case Series.

OBJECTIVES: Tacrolimus is an immunosuppressive agent that has been proposed in the treatment of severe ulcerative colitis. The present study examined the effectiveness and safety of tacrolimus in treating refractory Crohn disease (CD) colitis in children. METHODS: All children treated by oral tacrolimus for CD colitis at a tertiary pediatric center were included in the study. All patients were refractory to steroids and infliximab. Clinical response (decreased pediatric CD activity index [PCDAI] >15 and PCDAI <30) and remission (PCDAI <10) were monitored at 2, 4, 6, 12, and 24 months after induction. Tacrolimus blood levels and adverse effects were also noted. RESULTS: Among 220 patients with CD, 8 children (including 3 girls, median age 14 [9.5-18] years) were registered with a median PCDAI of 58.7 (32.5-65) before tacrolimus initiation. In patients treated with tacrolimus, the overall clinical response rates were 6/8, 3/8, 2/8, 2/8, and 1/8 with a remission rate of 4/8, 0/8, 0/8, 2/8, and 0/8 at 2, 4, 6, 12, and 24 months, respectively. At 2 months, the PCDAI scores were lower than those at induction (median 11.2; P = 0.004) with the mean whole plasma level of tacrolimus being 8.75 ng/mL (5.9-10 ng/mL). Adverse events occurred in 6 of 8 patients, including renal dysfunction, insulin-dependent diabetes, paresthesia, and tremor. Tacrolimus interruption was required in 2 cases. CONCLUSIONS: Tacrolimus could be considered to transiently treat refractory CD colitis. Tacrolimus could be used as a "bridge" toward another medical option in pediatric CD, although its adverse events are frequent.

Unexpected overestimation of methotrexate plasma concentrations: analysis of a single center pediatric population.

BACKGROUND: At this center, therapeutic drug monitoring of methotrexate (MTX) used to be performed by fluorescence polarization immunoassay (FPIA). We observed an increasing number of unusual high MTX concentrations at 48 and 72 hours during a couple of years. This study aimed to identify the causes of this variation. METHODS: A retrospective analysis was conducted on 272 patients hospitalized between January 2008 and October 2012. The whole MTX use system was analyzed using Ishikawa's method. The proportion of MTX concentrations ≤0.2 µmole/L at 48 (P48h) and 72 hours (P72h) was recorded and compared between both FPIA and EMITSiemens assays. A χ or a Fisher exact test was used (α = 0.05). RESULTS: Because of an announced withdrawal of the FPIA reagent, the method was switched in 2009 to an immunoenzymatic technique (EMITSiemens). Both P48h and P72h dropped significantly after 2009 (P48h: 45% versus 5% and P72h: 91% versus 47%; P < 0.0001). The replacement of the EMITSiemens reagent by the EMITARK Diagnostics reagent in 2012 led to an increase in both P48h and P72h. No significant difference was found in the proportions of MTX ≤0.2 µmole/L concentrations between FPIA and EMITARK Diagnostics at 48 (45% and 40%; P = 0.556) and 72 hours (91% and 100%; P = 0.231). Both internal and external quality control assessments gave regular satisfactory results during the study period. Furthermore, the interassay comparisons that were performed with internal quality controls and spiked serum samples showed similar results at the time of both shifts. The other changes observed in the MTX circuit were not associated with MTX concentration variations. CONCLUSIONS: The overestimation of the plasma concentration of MTX was concluded to be because of the assay reagent. A further study is consequently necessary to assess the impact of this analytical pitfall on the patients' survival.

In-line filtration in very preterm neonates: a randomized controlled trial.

In-line filtration is increasingly used in critically-ill infants but its benefits, by preventing micro-particle infusion in very preterm neonates, remain to be demonstrated. We conducted a randomized controlled trial among very preterm infants allocated to receive either in-line filtration of all the intra-venous lines or standard care without filters. The primary outcome was differences greater than 20% in the median changes in pro-inflammatory cytokine serum concentrations measured at day 3 and day 8 (+/-1) using a Luminex multianalytic profiling technique. Major neonatal complications were analyzed as secondary predefined outcomes. We randomized 146 infants, assigned to filter (n = 73) or control (n = 73) group. Difference over 20% in pro-inflammatory cytokine concentration between day 3 and day 8 was not found statistically different between the two groups, both in intent-to-treat (with imputation) and per protocol (without imputation) analyses. The incidences of most of neonatal complications were found to be similar. Hence, this trial did not evidence a beneficial effect of in-line filtration in very preterm infants on the inflammatory response syndrome and neonatal morbidities. These data should be interpreted according to local standards in infusion preparation and central line management.