Risk Of Non-persistence Research Articles

Early discontinuation of tamoxifen and aromatase inhibitors (AIs) by postmenopausal women with early-stage breast cancer.

524 Background: In women with early stage, hormone responsive breast cancer, compliance with adjuvant endocrine therapy is important for optimal outcomes. Prior studies, focused mostly on tamoxifen, have suggested suboptimal compliance, but compliance to AI therapy is little studied. We studied rates and predictors of nonpersistence in women aged 65 years and older who were treated with tamoxifen and/or AIs. Methods: A series of four telephone surveys were administered to community-dwelling women (age 65 to 89 years, median age 72) residing in 4 large states, who had initial treatment for early-stage breast cancer in 2003. The surveys, administered from 2005 to 2008, assessed demographic, socioeconomic and health factors, along with cancer treatment details, including use of adjuvant endocrine therapy. Nonpersistence was defined as a gap in adjuvant endocrine therapy of more than 60 days. Medication stop, start and switch dates were determined from survey responses. Cox proportional hazards models were used to identify patient and treatment factors that predicted nonpersistence. Results: In our cohort of 1,402 women, 55% were initially prescribed AIs, 45% tamoxifen. With median followup 59 months, 325 women (23%) discontinued treatment early (prior to 5 years). Among the 325 nonpersistent subjects, 27% discontinued therapy in the first year. Age over 80 years predicted non-persistence, risk ratio (RR) of 1.61 (p < 0.05), with a trend toward nonpersistence in women over 75 – RR 1.36 (p = 0.07). Patients in the lowest quartile of income (< $15K) had higher risk of nonpersistence (p = 0.002). Initial endocrine therapy (tamoxifen vs. AIs) was not predictive of nonpersistence. However, patients on AI's at censoring had lower nonpersistence risk, of borderline statistical significance (RR 0.80, p = 0.06). Race, marital status, education, stage, comorbidity, and type of surgery were not predictive of nonpersistence. Conclusions: Our study shows that noncompliance with standard adjuvant endocrine therapy is common in the current treatment environment. Older age and lowest income levels are associated with non-persistence. Women on AIs may be at less risk for nonpersistence. No significant financial relationships to disclose.

Comparing adherence and persistence across 6 chronic medication classes.

The National Quality Forum recently endorsed the proportion of days covered (PDC)-a measure of medication adherence-as an indicator of quality in drug therapy management. To inform initial efforts to improve the quality of drug therapy management, we compared PDC and persistence among new users of 6 commonly used chronic medication categories. A retrospective analysis of pharmacy claims in a database of more than 64 million members enrolled in 100 health plans assessed persistence and adherence to drug therapy in 6 chronic conditions. Patients were included in the analysis if they initiated a prescription drug of interest in any of 6 drug classes-prostaglandin analogs, statins, bisphosphonates, oral antidiabetics, angiotensin II receptor blockers (ARBs), and overactive bladder (OAB) medications-between January 1 and December 31, 2005. The first claim for a drug of interest during this period was considered a patient's index date. Patients were required to have a minimum of 12 months of continuous enrollment both preceding and following their index date. New users of a treatment were identified by excluding patients who filled a prescription for any drug in the same class during the previous 12 months and were followed for a minimum of 12 months. Nonpersistence was defined as discontinuation of the therapy class following an allowed gap between refills-30-, 60-, and 90-day refill gaps were used. Adherence was defined as a continuous measure of the proportion of days covered (PDC) during the 12-month post-index period. Logistic regression analyses predicted (a) nonpersistence during the 12-month post-index period and (b) adherence (PDC) of at least 80%, with drug class as the predictor variable of interest, controlling for demographic variables, insurance and plan type, history of hospitalization, Charlson comorbidity score, copayment for index medication, and number of medications at index. A total of 167,907 patients were identified across 6 cohorts. Using the 60-day gap, 6-month persistence rates were prostaglandin analogs 47%, statins 56%, bisphosphonates 56%, oral antidiabetics 66%, ARBs 63%, and OAB medications 28%. After the first 90 days of therapy, relative persistence was stable across cohorts, and rates declined consistently from 6 months post-index to study end. Logistic regression models showed that oral antidiabetic users had a 59%, 36%, 37%, and 79% decreased risk of nonpersistence in a 12-month follow-up period compared with patients taking prostaglandin analogs, statins, bisphosphonates, or OAB medications, respectively. Risk of nonpersistence decreased with increasing age. Mean (SD) 12-month adherence rates were: prostaglandin analogs 37% (26%), statins 61% (33%), bisphosphonates 60% (34%), oral antidiabetics 72% (32%), ARBs 66% (32%), and OAB medications 35% (32%). Logistic regression indicated that oral antidiabetic use was a significant predictor of adherence (PDC) of at least 80% compared with other therapy classes. Adjusted odds ratios for oral antidiabetics were 17.60 (95% confidence interval [CI] = 15.38-20.14) versus prostaglandin analogs, 2.06 (95% CI = 1.99-2.12) versus statins, 1.92 (95% CI = 1.83-2.02) versus bisphosphonates, 1.29 (95% CI = 1.24-1.34) versus ARBs, and 5.77 (95% CI = 5.38-6.19) versus OAB medications. This analysis of adherence (PDC) and persistence across a sample of 6 chronic therapies found variable but uniformly suboptimal medication use. Adherence to prostaglandin eye drops and OAB medications was lower than to cardiovascular, oral antidiabetic, and oral osteoporosis therapies. These findings provide useful baseline information for the development of initiatives to improve the quality of drug therapy management.

Risk of discontinuation of risperidone after exposure to potentially interacting drugs: A nested case-control study in patients with schizophrenia

Background: The cytochrome P450 (CYP) 2D6 and 3A4 isozymes play an important role in the metabolism of risperidone. Concurrent use of drugs that inhibit or induce the action of these enzymes may increase or decrease levels of risperidone, thereby increasing the risk for discontinuation of risperidone or the need for supplemental treatment to control disease symptoms. Objective: This study examined the association between exposure to potentially interacting drugs and nonpersistence in a cohort of patients with schizophrenia newly starting treatment with risperidone. Methods: The data for this nested case-control study were obtained from the administrative health databases of the Régie de l'Assurance Maladie de Québec. The base cohort included patients aged ≥15 years who began treatment with risperidone between July 2001 and December 2004. Cases consisted of those who were nonpersistent with risperidone either through drug discontinuation or the addition of/switch to a different atypical antipsychotic; noncases were those who persisted with risperidone through the end of their follow-up period. Exposure to CYP-inhibiting or CYP-inducing medications in the 1-, 3-, and 6-month windows before nonpersistence was compared between cases and noncases. The association between exposure to interacting medications and nonpersistence was analyzed using conditional logistic regression models to account for matching by time on treatment. Results: The base cohort included 20,840 patients, of whom 59.2% were female and 57.7% were aged ≥65 years. Nonpersistence occurred in 10,913 patients (52.4%) during the study period. Between 40% and 50% of patients were exposed to potential CYP inhibitors, and 6% to 10% were exposed to potential CYP inducers. Exposure to CYP inhibitors over 3 and 6 months was associated with an increase in risk for nonpersistence of ~10% (odds ratio [OR] for 3-month exposure = 1.10 [95% CI, 1.06-1.14]; OR for 6-month exposure = 1.11 [95% CI, 1.07-1.15]), whereas exposure to CYP inducers was not associated with a significant change in risk. Exposure to potentially interacting drugs was more likely to lead to nonpersistence while patients were still new to risperidone (ie, in the first month of treatment). For instance, the OR for 6-month exposure to inhibiting drugs was 1.20 (95% CI, 1.04-1.39) in the 1st month of treatment and 1.11 (95% CI, 1.01-1.20) between the 6th and 12th months. Conclusion: In this study, use of medications that are potential inhibitors of CYP2D6 and CYP3A4 appeared to be associated with an increased risk of nonpersistence with risperidone, particularly while patients were still new to treatment.

PDB69 DETERMINANTS OF STOPPING TREATMENT WITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE

DETERMINANTS OF STOPPINGTREATMENTWITH ORAL ANTIDIABETIC DRUGS IN DAILY CLINICAL PRACTICE Koerselman J, van der Bij S, Erkens JA, Kessabi S, Groot MT, Penning-van Beest FJA, Herings RMC PHARMO Institute, Utrecht, Utrecht,The Netherlands, Novartis Pharma AG, Basel, Switzerland, Novartis Pharma B.V, Arnhem,The Netherlands OBJECTIVES: In daily practice many Type 2 Diabetes Mellitus (T2DM-)patients discontinue treatment. Therefore, the aim of this study was to investigate the determinants of (non-) persistence with oral antidiabetic drugs (OADs) in daily clinical practice. METHODS: From the PHARMO record linkage system, comprising among others linked drug-dispensing, and hospital data for >2.3 million subjects in The Netherlands, new users of OADs were identified in the period 1999–2005. Patients with 1 year of follow-up, were included in the study-cohort. Persistence with OAD-treatment in the first year of therapy was determined using the method of Catalan. Potential determinants of (non-)persistence included patient-characteristics, type of initial OAD-therapy, and cardiovascular co-morbidity. RESULTS: The study included 33,299 new users of OADs. One year after start, 42% of new T2DM-patients had stopped using any OAD. The risk of non-persistence was decreased with male gender (HR: 0.97; 95% CI: 0.94–1.00), and cardiovascular drug use (HR: 0.91; 95% CI: 0.86–0.97). Regarding age, compared to patients 76 years, the age-group 55–75 years had a 16% lower risk, and the age-group 30–44 years had a 32% increased risk of non-persistence. Patients starting on combined metformin + SU had a lower risk of non-persistence with any OAD; compared to patients starting on metformin monotherapy, the risk was 23% lower (HR: 0.77; 95% CI: 0.70–0.85). The risk of nonpersistence was increased with a specialist as first prescriber (HR: 1.20; 95% CI: 1.15–1.26), higher initial daily dose (HR: 1.09; 95% CI: 1.00–1.22), and higher initial daily dosing frequency (HR: 1.10; 95% CI: 1.02–1.20). CONCLUSION: In daily clinical practice about 40% of new T2DM-patients stop OADtherapy within one year. Determinants of stopping OADmedication were male gender, age-group, specialist as first prescriber, dosing, cardiovascular drug-use, and type of initial OAD-treatment.