Pharmacokinetic and clinical monitoring through posologic changes in adalimumab intensification regimen from 40 mg every week to 80 mg every other week

Background: adalimumab dose escalation is often recommended for inflammatory bowel disease (IBD) patients incases of loss of response (LOR). The usual adalimumabintensification regimen was 40 mg every week. Recently,the pharmaceutical companies commercialized the 80 mginjection pen. In the biosimilars era, this pen was sold atthe same price as the 40 mg pen. Due to this and for patientcomfort, we proposed that our stable intensified adalimumab patients on a 40 mg every-week (ew) regimen change toa dose of 80 mg every-other-week (eow).Aim and methods: an observational study was performedto monitor outcome through this posologic change. Clinical,analytic parameters and adalimumab trough levels wereprospectively obtained at baseline, four and 12 monthsafter posologic change. The evolution of this cohort andcalculates savings were described.Results: thirteen patients were included in the study and themedian time of adalimumab intensification prior to posologic change to 80 mg eow was 32 months (IQR 29-63). Atfour months, all patients maintained adalimumab 80 mgeow. After month 4, two patients returned to the previousregimen after mild worsening, without significant changes in C-reactive protein (CRP), calprotectin or adalimumab-trough-levels. At one year, adalimumab was stoppedin one patient in remission with undetectable levels andpositive adalimumab-antibodies. No significant differencesin adalimumab-trough-levels were noted before and afterthe posologic change. Costs fell from 16,276 €/patient/yearof treatment to 8,812.15 €/patient/year of treatment.Conclusion: in IBD patients with stable response to adalimumab intensification regimen of 40 mg ew, changingto 80 mg eow seems to maintain response and similaradalimumab-trough-levels. Furthermore, it is cost-saving,although some patients may perceive mild symptoms. (AU)

Pharmacokinetic and clinical monitoring through posologic changes in adalimumab intensification regimen from 40 mg every week to 80 mg every other week.

BACKGROUND: Adalimumab dose escalation is often recommended for inflammatory bowel disease patients in cases of loss of response. The usual adalimumab intensification regimen was 40 mg every week. Recently the pharmaceutical companies commercialized the 80mg injection pen. In the biosimilars era, this pen was sold at the same price as the 40mg pen. Due to this and for patient comfort, we proposed that our stable intensified adalimumab patients on a 40mg every-week regimen, change to a dose of 80mg every-other-week. AIM AND METHODS: an observational study was performed to monitor outcome through this posologic change. Clinical, analytic parameters and adalimumab trough levels were prospectively obtained at baseline, 4 and 12 months after posologic change. The evolution of this cohort and calculates savings were described. RESULTS: 13 patients were included in the study and the median time of adalimumab intensification prior to posologic change to 80mg eow was 32 months (IQR 29-63). At 4 months, all patients maintained adalimumab 80mg every-other-week. After month 4, two patients returned to the previous regimen after mild worsening, without significant changes in CRP, calprotectin or adalimumab-trough-levels. At 1 year, adalimumab was stopped in one patient in remission with undetectable levels and positive adalimumab-antibodies. No significant differences in adalimumab-trough-levels were noted before and after the posologic change. Costs fell from 16276 €/patient/year of treatment to 8812.15 €/patient/year of treatment. CONCLUSION: In IBD patients with stable response to adalimumab intensification regimen of 40 mg every-week, changing to 80mg every-other-week seems to maintain response and similar adalimumab-trough-levels. Furthermore, it is cost-saving, although some patients may perceive mild symptoms.

Management of Everolimus and Voriconazole Interaction in Lung Transplant Patients.

BACKGROUND: To analyze the impact of voriconazole administration on everolimus dose, trough concentrations and concentration/dose (C0/D) ratio in order to determine the appropriate management of this interaction in lung transplant patients. METHODS: A retrospective study of 16 of consecutive lung transplant patients on a stable everolimus-based regimen to which oral voriconazole was added from January 2013 to February 2014. Everolimus blood levels were measured using the Thermo Scientific QMS Everolimus Immunoassay on an ARCHITECT-C8000 analyzer. The Wilcoxon signed-rank test was used to assess the exposure parameter variations before, during, and after azole withdrawal. A statistical analysis was performed using SPSS version 19.0. P-value < 0.05 was considered statistically significant. RESULTS: Sixteen patients were included. Voriconazole treatment led to a significant 8.7-fold increase in the everolimus C0/D ratio. Although initially the daily dose was reduced to 48.5% ± 20.5%, and subsequently to 79.5% ± 7.1%, the desired therapeutic levels were achieved in all patients when it was decreased to 86.6% ± 3.9%. After its withdrawal, the C0/D ratio returned to values similar to the baseline situation. The comparison of exposure parameters studied at stable moments, before and after the completion of azole treatment with the cotreatment period, revealed significant changes (P < 0.05). CONCLUSIONS: Oral voriconazole is a strong inhibitor of everolimus metabolism, requiring a dose reduction of around 87%. At the time of azole withdrawal, the dose should be increased to achieve C0/D ratio values similar to the initial situation. In our clinical practice, for a safe coadministration, a preemptive decrease to 75% of everolimus dose with the first azole prescription is recommended. Close monitoring of the everolimus concentrations and corresponding dosage adjustments are necessary until the target levels are achieved during both periods.

[Pharmacokinetic monitoring as a new tool to individualize anti-TNF therapy]. / La monitorización farmacocinética como nueva herramienta para individualizar la terapia anti-TNF.

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