Persistence and adherence to disease modifying drugs among patients with multiple sclerosis.

OBJECTIVE: This retrospective database study aimed to evaluate the adherence of multiple sclerosis (MS) patients on immunomodulatory treatments using claims data, and to identify differences between compliance and persistency measurements in the context of this disease. METHODS: Continuously enrolled MS patients treated with subcutaneous IFNbeta-1b (Betaseron * ), subcutaneous IFNbeta-1a (Rebif dagger ), intramuscular IFNbeta-1a (Avonex double dagger ), and subcutaneous glatiramer acetate (Copaxone section sign ).) were identified from the PharMetrics patient-centric database, and all information related to patient demographics and pharmacy claims for the drugs of interest were extracted. OUTCOME MEASURES: The main outcomes were treatment switches and discontinuations for patients initiated on the drugs of interest. Various compliance and persistency metrics including the proportion of days covered, treatment prevalence at 6-monthly time points after initiation, and the continuous time on drug were also examined. RESULTS: A total of 6134 MS patients were started on one of the four drugs of interest. The number of patients switching or discontinuing therapy rose over the study period. The proportion of patients switching was similar between study drugs, by the different metrics, with the highest switch rates for subcutaneous IFNbeta-1b and the lowest for subcutaneous glatiramer acetate. Discontinuation rates were highest for subcutaneous IFNbeta-1b and lowest for intramuscular IFNbeta-1a. Regression models showed that intramuscular IFNbeta-1a and subcutaneous IFNbeta-1a had similar and higher persistency compared to subcutaneous IFNbeta-1b and subcutaneous glatiramer acetate. CONCLUSIONS: Although treatment switching and discontinuation is common in MS patients, there is some noticeable variability between drugs and across measures of persistency and adherence. Also, claims data do not allow distinguishing between clinical patterns of MS, direct estimation of disease severity and observation of care that occurs outside of insurance coverage, and results need to be cautiously interpreted. The compliance to the various MS drugs was 80% or higher at all times for all four drugs. The highest rate of treatment persistency existed in the intramuscular IFNbeta-1a initiator group, while subcutaneous IFNbeta-1b was associated with a significantly lower persistence (p < 0.0001).

Healthcare resource utilization following switch or discontinuation in multiple sclerosis patients on disease modifying drugs.

OBJECTIVE: The objective of this study was to explore the cost and utilization in the period following discontinuations or switches of disease modifying drugs (DMDs) for patients with multiple sclerosis (MS). Secondary objectives included an assessment of the time to switch or discontinuation from index DMD treatment. METHODS: Cases were defined as a billed MS diagnosis in continuously enrolled patients initiated with interferon-beta1a IM, interferon-beta1b SC, glatiramer acetate, and interferon-beta1a SC found in the PharMetrics Patient-Centric Database. Information on patient demographics, diagnoses, procedures, pharmacy-dispensed drugs, and costs was extracted; reasons for discontinuation and expenses outside of the healthcare system were not available. Treatment discontinuations and switches between study drugs were defined using pharmacy prescription patterns and analyzed by descriptive and regression methods. The non-pharmacy medical costs in the 18 months following switching or discontinuation were compared to the costs in a randomly selected similar period for those patients who did not switch or discontinue these agents. RESULTS: A total of 5,772 MS patients were continuously enrolled and were treated with one or more of the four drugs of interest, and about half of these patients switched drugs or discontinued treatment for at least 90 days. Patients initiated with interferon-beta1b SC were more likely to discontinue treatment compared to interferon-beta1a IM users. Non-pharmaceutical medical costs were highest for those switching treatments followed by those discontinuing DMDs in the 18 months following a switch or discontinuation, compared to persistent users of these drugs. Interferon beta1b SC initiators had higher costs following changes or discontinuations, while glatiramer acetate and interferon-beta1a SC users had lower subsequent costs compared to interferon-beta1a IM users. LIMITATIONS: Unfortunately, the reasons for stopping the initial treatment cannot be determined from analysis of an administrative claims database. Also, the MS cases followed in this analysis are billing diagnostic events unconfirmed through a review of medical records or other data sources. The results are unstratified in terms of severity and thus while treatment patterns may vary for patients with different types of MS (e.g., progressive vs. relapsing-remitting), this cannot be examined in this analysis. CONCLUSION: Changing or discontinuing DMDs is common among MS patients and is associated with higher non-pharmaceutical medical costs that vary based on the initiating drug and other demographics characteristics.

The psychometric validation of the Sheehan Disability Scale (SDS) in patients with bipolar disorder.

Bipolar disorder (BD) adversely affects daily activities/functioning. The Sheehan Disability Scale (SDS) assesses disability in work/school activities, family relationships, and social functioning, and it evaluates the functional impact of psychiatric disorders. BD outpatients from 21 U.S. sites completed a battery of validated instruments (including the SDS) three times over 8-12 weeks. Instrument reliability (internal consistency, test-retest), validity (construct, convergent validity, known groups) and responsiveness were measured. There were missing data for the SDS in 2% of the 225 subjects with BD. One factor explained 82% of the variance. All SDS items had rotated factor loadings on the first factor >0.90, confirming the appropriateness of the SDS total score. Item-scale correlations surpassed 0.40. There was excellent internal consistency reliability for the SDS total score (Cronbach's alpha=0.89). Test-retest reliability was acceptable for the SDS total score (intraclass correlation coefficient=0.73). Correlations with other instruments demonstrate convergent and divergent validity. The SDS total and item scores significantly discriminated between (self-rated) overall health status, clinician-rated functional status, and clinician-rated depression, evidencing known group validity. The SDS demonstrated ability to detect change over time. The SDS is a valid, reliable measure of disability and is responsive to change over time when used in subjects with BD.

Comparing adherence to and persistence with antipsychotic therapy among patients with bipolar disorder.

BACKGROUND: Medication nonadherence is a significant problem among patients with bipolar disorder. OBJECTIVE: To compare adherence and persistence among patients with bipolar disorder initiated on antipsychotics in a state Medicaid system over a 12 month follow-up period. METHODS: Claims data for patients with bipolar disorder from a de-identified Medicaid database were examined. Patients were classified into 4 monotherapy treatment groups (risperidone, olanzapine, quetiapine, or typical antipsychotic) based on the first prescription filled between January 1, 1999, and December 31, 2001. Adherence and persistence were analyzed over a 12 month follow-up period. Adherence was measured using the Medication Possession Ratio (MPR). Persistence was defined as the total number of days from the initiation of treatment to therapy modification (ie, discontinuation, switching, or combination with another antipsychotic). Adjustment for confounding variables was undertaken using ordinary least-squares and Cox proportional hazard regression modeling. RESULTS: The mean MPRs were 0.68 for risperidone (n = 231), 0.68 for olanzapine (n = 283), 0.71 for quetiapine (n = 106), and 0.46 for typical antipsychotics (n = 205). Patients initiated on typical antipsychotics were 23.6% less adherent than patients initiated on risperidone (p < 0.001). Mean persistence (days) was 194.8 for risperidone, 200.9 for olanzapine, 219.8 for quetiapine, and 179.2 for typical antipsychotics. Extended Cox regression modeling indicated no significant differences between antipsychotics in hazards of therapy modification within 250 days of initiation. However, patients initiated on typical antipsychotics were 5.2 times more likely to modify therapy compared with those initiated on risperidone after 250 days of antipsychotic therapy (p < 0.001). CONCLUSIONS: Adherence and persistence were similar between atypical antipsychotic groups. The typical antipsychotic group, however, demonstrated lower adherence and a greater likelihood of patients modifying therapy compared with the risperidone cohort.

Hospitalization risks in the treatment of bipolar disorder: comparison of antipsychotic medications.

OBJECTIVES: This study compared the relative risk for hospitalization of patients with bipolar and manic disorders receiving atypical and typical antipsychotics. METHODS: This retrospective study was based on administrative claims data extracted from the PharMetrics database during 1999 through 2003. Comparisons were made among atypical antipsychotics (risperidone, olanzapine, quetiapine or ziprasidone), as well as between each of these versus a combined group of the leading typical antipsychotics. Relative risk for hospitalization was estimated with Cox proportional regression, which adjusted for differences in patient characteristics. RESULTS: Risperidone and olanzapine demonstrated higher risks for hospitalization than quetiapine [hazard ratio (HR) 1.19, p < 0.05 for both], translating into higher annual mental health inpatient charges of $260 per patient. Risperidone and olanzapine also showed higher estimated risks than ziprasidone, which approached the p < 0.05 threshold. Differences between each of the atypicals and the combined typicals were not significant. Patients with putative rapid cycling had a threefold greater risk for hospitalization than other patients with bipolar disorder. In these patients, comparisons among atypical antipsychotics showed that risperidone had a significantly higher hospitalization risk than olanzapine (HR 3.31, p < 0.05), resulting in higher annual mental health inpatient charges of $4,930 per patient. CONCLUSIONS: In the treatment of bipolar and manic disorders, risperidone and olanzapine were associated with a higher risk for hospitalization than quetiapine, and possibly ziprasidone. In the treatment of putative rapid cyclers, olanzapine was associated with a lower risk for hospitalization than risperidone.

Economic outcomes associated with atypical antipsychotics in bipolar disorder: a systematic review.

OBJECTIVE: Bipolar disorder is a serious condition that is costly to the health care system. Atypical antipsychotics are more expensive than conventional treatments. From a policy-making perspective, the additional cost must be justified by improved outcomes. The objective of this study was to conduct a systematic review to determine the relative costs and cost-effectiveness associated with atypical antipsychotics in bipolar disorder. DATA SOURCES: We conducted a systematic review of the literature in PubMed and EMBASE from January 1985 through October 2005, including published studies and conference proceedings. Databases were searched using predefined terms. STUDY SELECTION: Studies were included if they were claims data analyses, trial-based economic evaluations, or cost-effectiveness analyses using models. Data were extracted using predefined tables. DATA SYNTHESIS: Fourteen studies were identified. Seven were medical claims database analyses, 4 were trial-based economic evaluations, and 3 were cost-effectiveness models. Eight of these studies were conference proceedings. The studies did not provide sufficient information to determine any ranking of interventions in terms of least to most costly in overall resource consumption or in terms of their relative cost-effectiveness. Where comparable, results tended to be inconsistent. CONCLUSION: There is a scarcity of economic studies in this field. A reference case outlining how to address the complex interplay between effectiveness, safety, adherence, and quality of life and their impact on resource use and costs is needed to contribute to improving the treatment of patients with bipolar disorder while making the best use of scarce health resources.

Racial differences in medication switching and concomitant prescriptions in the treatment of bipolar disorder.

OBJECTIVE: This study examined whether the practices of switching between classes of medications and prescription of concomitant medications differed between black and non-black patients with bipolar disorders. METHODS: In a retrospective cohort design, data from 1998 to 2004 for patients with diagnoses of bipolar disorders were obtained from a large claims database. Information was obtained on the number of prescriptions for four classes of medications (anticonvulsants, mood stabilizers, and first- and second-generation antipsychotics) as well as on medication switching (between drug classes), concomitant prescriptions, resource use, and outcomes (an emergency department visit or a hospitalization). Logistic models assessed the relationship between outcomes and switching or concomitant prescriptions. RESULTS: The study population consisted of 1,113 adults who received at least one prescription from the four drug classes. Medication switching or concomitant prescriptions were documented for more than one-third of patients (36.6 percent). A significantly greater proportion of black patients received two or more medications from different drug classes (41.1 compared with 34.7 percent). The number of prescriptions was lower for black patients than for non-black patients. Patients for whom switching or concomitant prescriptions were documented were significantly more likely to have an emergency department visit or a hospitalization, and race was a significant predictor of these outcomes. CONCLUSIONS: The prevalence of polypharmacy-medication switching and concomitant prescriptions-was high among patients with bipolar disorder, with a higher prevalence among black patients. Patients who experienced switching or concomitant prescriptions were more likely to visit the emergency department or to be hospitalized.