Predictors of non-adherence with oral bisphosphonates: an Italian retrospective cohort study on administrative databases

Background. In clinical trials, adherence with oral anti-osteoporotic therapies is generally high, in contrast with the clinical practice post-authorization. Poor adherence to oral bisphosphonates leads to reduced medication efficacy, exposure to unjustified adverse reactions and raised the health expenditure. Reasons for non-adherent behaviour could include: difficulty taking medication as prescribed, experience of adverse effect and worry of long term harm, scepticism of drug effectiveness and poor perception of the disease consequences (Silverman et al. 2011). The objectives of this study were to quantify the proportion of non-adherent subjects and to define predictors of non-adherence with bisphosphonates in order to develop possible interventions to improve compliance. Methods. A retrospective cohort study has been conducted using administrative database of 13 units joined in the Italian BEST (Bisphosphonate Effectiveness Safety Trade-off) study, accounting for 18 million inhabitants. Patients with at least 2 prescriptions of oral bisphosphonates through 2003–2007 were selected. Exclusion criteria were age <40, Paget’s disease and cancer. Demographic details, hospitalization and co-medication data were obtained by a record linkage methodology. Adherence was measured for each patient over the entire observation period (from the first bisphosphontate prescription to the end of observation for death, switch to other anti-osteoporotic therapies or end of the study) by Medication Possession Ratio (MPR). The MPR was defined as the sum of days of supply of all oral bisphosphonates divided by the potential number of days of therapy in that period (Steiner et al. 1997). A subject was defined adherent when MPR was ³80% in each year. The primary outcome of the study was the lack of adherence. A multiple logistic regression model was performed by SAS 9.2, in order to identify potential predictors of non-adherent regimen. Results. Among 191,829 users of oral bisphosphonates, 142,972 (74%) were non-adherent to drug therapy. The multivariable analysis showed that the risk of non-adherence was higher with daily dosing formulation in comparison to weekly dosing (OR 1.25; CI95% 1.18-1.31) and was also increased with alendronic acid plain preparation as compared with its fixed combination with colecalciferol (1.26; 1.21-1.31). The co-medication with the following therapeutic classes showed an increased non-adherence risk: FANS (1.09; 1.06-1.13), PPI (1.13; 1.10-1.15), antiepileptics (1.07; 1.04-1.11), antidepressants (1.15; 1.12-1.17) or antithrombotic agents (1.06; 1.04-1.09). Moreover hospitalization for any reasons increased the risk of non-adherence (1.12; 1.09-1.15). Determinants for decreased non-adherence odds were: higher age and previous spine, femur, wrist and ribs fractures; instead, hip fractures were associated with increased risk of non-adherence (1.07; 1.01-1.14). Conclusion. This study found a suboptimal adherence in oral bisphosphonate users and revealed several predictors of non-adherent behaviour. Future interventions could be addressed to modify these determinants in order to improve adherence and consequently effectiveness of oral bisphosphonates in osteoporosis.