Efficacy of a reduced pill burden on therapeutic adherence to calcineurin inhibitors in renal transplant recipients: an observational study

Abstract

Purpose: The aim of this study was to determine the prevalence of nonadherence in a cohort of renal transplant recipients (RTRs) and to evaluate prospectively whether more intense clinical surveillance and reduced pill number enhanced adherence.

Patients and methods: The study was carried out in 310 stable RTRs in whom adherence, life satisfaction, and transplant care were evaluated by specific questionnaires (time 0). The patients under tacrolimus (TAC; bis in die [BID]) were then shifted to once-daily TAC (D-TAC) to reduce their pill burden (Shift group) and were followed up for 6 months to reevaluate the same parameters. Patients on cyclosporin or still on BID-TAC constituted a time-control group.

Results: The prevalence of nonadherence was 23.5% and was associated with previous rejection episodes (P<0.002), and was inversely related to Life Satisfaction Index, anxiety, and low glomerular filtration rate (minimum P<0.03). Nonadherent patients were significantly less satisfied with their medical care and their relationships with the medical staff. A shift from BID-TAC to D-TAC was performed in 121 patients, and the questionnaires were repeated after 3 and 6 months. In the Shift group, a reduction in pill number was observed (P<0.01), associated with improved adherence after 3 and 6 months (+36%, P<0.05 versus basal), with no change in controls. Decreased TAC trough levels after 3 and 6 months (-9%), despite a slight increase in drug dosage (+6.5%), were observed in the Shift group, with no clinical side effects.

Conclusion: The reduced pill burden improves patients' compliance to calcineurin-inhibitors, but major efforts in preventing nonadherence are needed.

Keywords: adherence; calcineurin inhibitors; once-daily tacrolimus; renal transplant.

Figure 1

Flowchart of the study. Abbreviations: BID-TAC, twice a day; CYA, cyclosporine; C-S, cross-sectional; PR, prospective; Shift, patients shifted from BID-TAC to once-daily TAC; Control, time-control group.

Figure 2

Prevalence of nonadherence in the two groups under study throughout the observation period, expressed as percentage value; the absolute number of patients is reported in columns (T0 = basal; T3 and T6 = after 3 and 6 months of follow-up, respectively). Note: *P<0.05 versus T0.

Figure 3

Doses (blue line) and trough levels (red line) of once-daily tacrolimus (D-TAC) throughout the observation period in patients of the Shift group. T0 represents the mean value of the last three bis in die TAC trough levels and doses before the shift; 1W and 2W represent the determinations of trough levels 1 week and 15 days after the shift and the consequent changes in D-TAC doses; T3 and T6 represent the modifications in D-TAC trough levels after 3 and 6 months of follow-up, when the doses of D-TAC were fixed. Notes: *P<0.003, T3 and T6 versus T0, †P<0.003 versus T0.