Interventions to Increase Adherence in Patients Taking Immunosuppressive Drugs After Kidney Transplantation: a Systematic Review of Controlled Trials

Background: Immunosuppressive drugs have to be taken through the whole duration of kidney transplant survival to avoid rejection. Low adherence can increase the risk of allograft rejection. The objective was to evaluate the effectiveness of adherence-enhancing interventions (AEI) in kidney transplantation recipients taking immunosuppressive drugs.

Methods: A search was performed in Medline, Embase, CINAHL, and PsycINFO. The search was performed in May 2016. We included comparative studies on AEI for kidney transplant recipients taking immunosuppressive drugs. The primary outcome was medication adherence. All identified articles were screened according to the predefined inclusion criteria. The risk of bias was assessed with the Cochrane risk of bias tool. Study selection and risk of bias assessment were performed by two reviewers independently. Data were extracted in standardized tables. Data extraction was verified by a second reviewer. All discrepancies were resolved through discussion. Data were synthesized in a structured narrative way. There is no registered or published protocol for this systematic review.

Results: We identified 12 studies. The number of participants ranged from 24 to 1830. Nine studies included adults, two children, and one adults and children. Risk of bias was high. The main reasons for high risk of bias were inadequate allocation sequence (confounding) and that studies were not blinded. Eleven studies evaluated AEI consisting of educational and/or behavioral components. All these studies showed an effect direction in favor of the intervention. Intervention effect was only moderate. Most adherence measures in studies on educational and behavioral interventions showed statistically significant differences. Studies that combined educational and behavioral intervention components showed larger effects. All studies that were statistically significant were multimodal. Studies that included an individualized component and more intensive interventions showed larger effects. One study evaluated a reminder system. Effect size was not reported. This study showed no statistical significant difference (p > 0.05).

Conclusion: Educational and behavioral AEI can increase adherence. In particular, multimodal and individualized interventions seem promising. However, because of the small effect, the high risk of bias, and the invalidity of adherence measures, the actual benefit of adherence interventions for an unselected patient population (i.e., including also adherent patients) seems limited. No conclusion is possible for interventions combining adherence-enhancing components that address intentional (behavioral) as well as unintentional adherence (reminder).