METHODS RESULTS. Supported by funding from Ortho-McNeil Janssen Scientific Affairs, LLC

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PREDICTORS OF MEDICATION ADHERENCE AMONG PATIENTS WITH SCHIZOPHRENIC DISORDERS TREATED WITH TYPICAL AND ATYPICAL ANTIPSYCHOTICS IN A LARGE STATE MEDICAID PROGRAM S.P. Lee 1 ; K. Lang 2 ; J. Jackel 2 ; C. Crivera 1 ; R. Dirani 1 ; J. Menzin 2 1 Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 2 Boston Health Economics, Inc. Waltham, MA, USA INTRODUCTION Schizophrenic disorders afflict approximately 1.1% of the adult population, or 2.4 million people in the United States 1 Symptoms range from hallucinations or delusions to problems expressing emotion, communicating, developing plans or finding pleasure in daily activities 2 Nonadherence to therapy is common when continued use of a drug is required for daily functioning Reasons for nonadherence include forgetting to take the medication, feeling that the medication is unnecessary or disliking the resulting side effects Nonadherent patients with schizophrenic disorders are more likely to experience relapse of symptoms and repeated hospitalization 3,4 OBJECTIVES To evaluate antipsychotic treatment among Florida Medicaid beneficiaries with schizophrenic disorders and to identify factors associated with treatment adherence METHODS Data Source Florida Medicaid is the nation s fourth largest Medicaid provider, with more than 3.1 million recipients The database consists of two files: --Eligibility file: contains information on monthly eligibility, dual Medicare eligibility status, and patient demographics --Claims detail file: contains details on medical and pharmacy utilization, including ICD-9-CM diagnosis and procedure codes, national drug code (NDC), type of service, date of service, and treatment provider Patient Selection and Follow-up Patients were included in the analysis if they: --Received at least two prescriptions for an antipsychotic medication and had at least one inpatient or two outpatient claims indicating schizophrenia or schizoaffective disorder between July 1, 2004, and June 31, 2005 (first antipsychotic termed index date ) --Were eligible for Medicaid in the 12 months before and after their index date and were not dually eligible for Medicare and Medicaid benefits during this period Patients were followed for 1 year before the index date (baseline period) to 1 year after the index date (follow-up period) Study Measures Type of antipsychotic treatment received: --Injectable atypical: received any injectable atypical antipsychotic without regard to other antipsychotics received --Injectable typical: received any injectable typical antipsychotic and did not receive an injectable atypical antipsychotic --Oral atypical and typical: received both oral typical and atypical antipsychotics and received no injectable antipsychotics --Oral atypical: received oral atypical antipsychotics only --Oral typical: received oral typical antipsychotics only Treatment adherence included: --Medication possession ratio (MPR): unduplicated non-hospitalized treatment days divided by the number of non-hospitalized days in the period --Persistence: days between the last fill date plus days of medication in last fill divided by the number of days remaining in the period after the first antipsychotic --Consistence: the weighted average of the number of days treated with a specific antipsychotic divided by the duration of time from the first to last antipsychotic --Maximum gap in therapy: the maximum number of consecutive untreated days Data Analyses Descriptive analyses of patient demographics and treatment characteristics in the baseline period were conducted Adherence measures were evaluated in terms of the mean (± SD) Stratified adherence analyses by type of antipsychotic were performed Logistic regressions were used to identify predictors of nonadherence, defined as MPR <0.80 Variables included in the multivariate regression analysis were selected based on review of the literature All analyses were conducted using SAS version 9.1 (SAS Institute, Cary, NC) RESULTS Patient Demographics A total of 12,032 patients met the study inclusion criteria ( Table 1) In the 12 months before index, 17.9% of patients had a substance abuse diagnosis and 38.7% had other psychotic conditions (ICD-9-CM codes 290.xx to 299.xx excluding 295.xx) Table 1. Demographic Characteristics Among Patients With Schizophrenic Disorders (N = 12,032). Age (%) <18 3.9% 18-34 20.1% 35-44 24.7% 45-64 49.4% 65+ 1.9% Mean (SD) 43.2 (13) Gender* (%) Male 47.5% Female 51.5% Race (%) Caucasian 37.5% Black 25.2% Other 37.2% *1.0% is missing gender. Baseline Treatment Characteristics The most common type of antipsychotic received during the baseline period was oral atypical only (60%), followed by oral typical, and oral atypical medications (13%) (Table 2) In the baseline period, 61.4% of patients received antidepressants and 50.2% received anxiolytics Supported by funding from Ortho-McNeil Janssen Scientific Affairs, LLC Table 2. Baseline Antipsychotic Treatment Patterns Among Patients With Schizophrenic Disorders. Type of antipsychotic medication received in baseline (%) Injectable atypical with or without other antipsychotic 2.4% Injectable typical with or without other antipsychotic 10.7% Oral typical antipsychotic only 5.7% Oral atypical antipsychotic only 60.0% Oral typical and atypical antipsychotic 12.5% No antipsychotics 8.6% Use of concomitant medications (%) Antidepressants 61.4% Anxiolytics 50.2% Mood stabilizers 5.8% Anticholinergic agents 43.3% New starts* (%) Yes 10.2% No 89.8% *Defined as patients who received their first antipsychotic medication at least 9 months after the start of the baseline period. Treatment Adherence in the Follow-up Period Treatment adherence measures during the follow-up period are summarized in Table 3 Table 3. Antipsychotic Treatment Adherence Measures During the Follow-up Period Among Patients With Schizophrenic Disorders. Type of antipsychotic medication received in follow-up period (%) Injectable atypical with or without other antipsychotic 5.3% Injectable typical with or without other antipsychotic 10.6% Oral typical antipsychotic only 5.3% Oral atypical antipsychotic only 64.7% Oral typical and atypical antipsychotic 14.0% MPR Percentage of patients with MPR between 0.8 and 1 67.5% Percentage of patients with MPR between 0.5 and <0.8 19.0% Percentage of patients with MPR less than 0.5 13.5% Mean (± SD) 0.8 (0.2) Mean (± SD) consistence 84.5 (16.3) Mean (± SD) persistence 94.2 (16.3) Mean (± SD) maximum gaps in therapy (days) 28.8 (41.3) MPR, consistence, persistence and maximum gaps in therapy were similar among patients treated with all antipsychotic treatment types Predictors of Nonadherence Table 4. Predictors of Nonadherence During the Follow-up Period Among Patients With Schizophrenic Disorders.* Parameter Odds Ratio 95% CI Aged <34 (vs aged 45+) 1.320 1.192-1.461 Aged 35-44 (vs aged 45+) 1.182 1.075-1.300 Baseline substance abuse diagnosis 1.576 1.422-1.747 Baseline other psychotic diagnosis 1.055 0.970-1.147 Baseline antidepressant use 1.593 1.309-1.939 Baseline anxiolytics use 1.375 1.155-1.637 Baseline mood altering use 1.691 1.031-2.774 Received atypical oral antipsychotic only 1.085 0.905-1.301 Received atypical and typical oral antipsychotics 0.774 0.629-0.953 Received injectable typical antipsychotics 1.299 1.053-1.603 Received injectable atypical antipsychotics 0.697 0.542-0.897 New starts (vs continuing users) 3.423 3.026-3.872 *Nonadherence was defined as a MPR < 0.8. Limitations Diagnoses of schizophrenic disorders could not be verified through chart reviews Confounding variables such as marital status could not be evaluated Results of this study may not be generalizable to other patient populations (eg, managed care) CONCLUSIONS Younger age, having a substance abuse diagnosis, receipt of concomitant antidepressant, anxiolytic or mood altering medications, newly starting treatment and receiving injectable conventional medications are predictive of poor adherence to antipsychotic therapy among patients with schizophrenic disorders These results may be useful for identifying patients at risk for medication nonadherence. Therefore, this analysis may help to identify patients for interventions aimed at increasing adherence These findings will be useful to state Medicaid agencies and physicians who treat patients with schizophrenic disorders REFERENCES 1. U.S. Department of Health and Human Services. National Institute of Health. Schizophrenia. 2007 Jan; 06-3517. Available at: www.nimh.gov/health/publications/schizophrenia/ schizophrenia-booklet---2006.pdf. Accessed April 7, 2008. 2. Valenstein M, Copeland LA, Blow FC, et al. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care. 002;40(8):630-639. 3. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004;161(4):692-699. 4. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv. 2001;52(6):805-811. Poster presented at the 13th International Meeting of the International Society for Pharmacoeconomics and Outcomes Research; May 3 7, 2008; Toronto, Canada.

INTRODUCTION Schizophrenic disorders afflict approximately 1.1% of the adult population, or 2.4 million people in the United States 1 Symptoms range from hallucinations or delusions to problems expressing emotion, communicating, developing plans or finding pleasure in daily activities 2 Nonadherence to therapy is common when continued use of a drug is required for daily functioning Reasons for nonadherence include forgetting to take the medication, feeling that the medication is unnecessary or disliking the resulting side effects Nonadherent patients with schizophrenic disorders are more likely to experience relapse of symptoms and repeated hospitalization 3,4 OBJECTIVES To evaluate antipsychotic treatment among Florida Medicaid beneficiaries with schizophrenic disorders and to identify factors associated with treatment adherence METHODS Data Source Florida Medicaid is the nation s fourth largest Medicaid provider, with more than 3.1 million recipients The database consists of two files: --Eligibility file: contains information on monthly eligibility, dual Medicare eligibility status, and patient demographics --Claims detail file: contains details on medical and pharmacy utilization, including ICD-9-CM diagnosis and procedure codes, national drug code (NDC), type of service, date of service, and treatment provider Patient Selection and Follow-up Patients were included in the analysis if they: --Received at least two prescriptions for an antipsychotic medication and had at least one inpatient or two outpatient claims indicating schizophrenia or schizoaffective disorder between July 1, 2004, and June 31, 2005 (first antipsychotic termed index date ) --Were eligible for Medicaid in the 12 months before and after their index date and were not dually eligible for Medicare and Medicaid benefits during this period Patients were followed for 1 year before the index date (baseline period) to 1 year after the index date (follow-up period) Study Measures Type of antipsychotic treatment received: --Injectable atypical: received any injectable atypical antipsychotic without regard to other antipsychotics received --Injectable typical: received any injectable typical antipsychotic and did not receive an injectable atypical antipsychotic --Oral atypical and typical: received both oral typical and atypical antipsychotics and received no injectable antipsychotics --Oral atypical: received oral atypical antipsychotics only --Oral typical: received oral typical antipsychotics only Treatment adherence included: --Medication possession ratio (MPR): unduplicated non-hospitalized treatment days divided by the number of non-hospitalized days in the period --Persistence: days between the last fill date plus days of medication in last fill divided by the number of days remaining in the period after the first antipsychotic --Consistence: the weighted average of the number of days treated with a specific antipsychotic divided by the duration of time from the first to last antipsychotic --Maximum gap in therapy: the maximum number of consecutive untreated days

Data Analyses Descriptive analyses of patient demographics and treatment characteristics in the baseline period were conducted Adherence measures were evaluated in terms of the mean (± SD) Stratified adherence analyses by type of antipsychotic were performed Logistic regressions were used to identify predictors of nonadherence, defined as MPR <0.80 Variables included in the multivariate regression analysis were selected based on review of the literature All analyses were conducted using SAS version 9.1 (SAS Institute, Cary, NC) RESULTS Patient Demographics A total of 12,032 patients met the study inclusion criteria ( Table 1) In the 12 months before index, 17.9% of patients had a substance abuse diagnosis and 38.7% had other psychotic conditions (ICD-9-CM codes 290.xx to 299.xx excluding 295.xx) Table 1. Demographic Characteristics Among Patients With Schizophrenic Disorders (N = 12,032). Age (%) <18 3.9% 18-34 20.1% 35-44 24.7% 45-64 49.4% 65+ 1.9% Mean (SD) 43.2 (13) Gender* (%) Male 47.5% Female 51.5% Race (%) Caucasian 37.5% Black 25.2% Other 37.2% *1.0% is missing gender. Baseline Treatment Characteristics The most common type of antipsychotic received during the baseline period was oral atypical only (60%), followed by oral typical, and oral atypical medications (13%) (Table 2) In the baseline period, 61.4% of patients received antidepressants and 50.2% received anxiolytics Supported by funding from Ortho-McNeil Janssen Scientific Affairs, LLC

Table 2. Baseline Antipsychotic Treatment Patterns Among Patients With Schizophrenic Disorders. Type of antipsychotic medication received in baseline (%) Injectable atypical with or without other antipsychotic 2.4% Injectable typical with or without other antipsychotic 10.7% Oral typical antipsychotic only 5.7% Oral atypical antipsychotic only 60.0% Oral typical and atypical antipsychotic 12.5% No antipsychotics 8.6% Use of concomitant medications (%) Antidepressants 61.4% Anxiolytics 50.2% Mood stabilizers 5.8% Anticholinergic agents 43.3% New starts* (%) Yes 10.2% No 89.8% *Defined as patients who received their first antipsychotic medication at least 9 months after the start of the baseline period. Treatment Adherence in the Follow-up Period Treatment adherence measures during the follow-up period are summarized in Table 3 Table 3. Antipsychotic Treatment Adherence Measures During the Follow-up Period Among Patients With Schizophrenic Disorders. Type of antipsychotic medication received in follow-up period (%) Injectable atypical with or without other antipsychotic 5.3% Injectable typical with or without other antipsychotic 10.6% Oral typical antipsychotic only 5.3% Oral atypical antipsychotic only 64.7% Oral typical and atypical antipsychotic 14.0% MPR Percentage of patients with MPR between 0.8 and 1 67.5% Percentage of patients with MPR between 0.5 and <0.8 19.0% Percentage of patients with MPR less than 0.5 13.5% Mean (± SD) 0.8 (0.2) Mean (± SD) consistence 84.5 (16.3) Mean (± SD) persistence 94.2 (16.3) Mean (± SD) maximum gaps in therapy (days) 28.8 (41.3) MPR, consistence, persistence and maximum gaps in therapy were similar among patients treated with all antipsychotic treatment types Predictors of Nonadherence

Predictors of Nonadherence Table 4. Predictors of Nonadherence During the Follow-up Period Among Patients With Schizophrenic Disorders.* Parameter Odds Ratio 95% CI Aged <34 (vs aged 45+) 1.320 1.192-1.461 Aged 35-44 (vs aged 45+) 1.182 1.075-1.300 Baseline substance abuse diagnosis 1.576 1.422-1.747 Baseline other psychotic diagnosis 1.055 0.970-1.147 Baseline antidepressant use 1.593 1.309-1.939 Baseline anxiolytics use 1.375 1.155-1.637 Baseline mood altering use 1.691 1.031-2.774 Received atypical oral antipsychotic only 1.085 0.905-1.301 Received atypical and typical oral antipsychotics 0.774 0.629-0.953 Received injectable typical antipsychotics 1.299 1.053-1.603 Received injectable atypical antipsychotics 0.697 0.542-0.897 New starts (vs continuing users) 3.423 3.026-3.872 *Nonadherence was defined as a MPR < 0.8. Limitations Diagnoses of schizophrenic disorders could not be verified through chart reviews Confounding variables such as marital status could not be evaluated Results of this study may not be generalizable to other patient populations (eg, managed care) CONCLUSIONS Younger age, having a substance abuse diagnosis, receipt of concomitant antidepressant, anxiolytic or mood altering medications, newly starting treatment and receiving injectable conventional medications are predictive of poor adherence to antipsychotic therapy among patients with schizophrenic disorders These results may be useful for identifying patients at risk for medication nonadherence. Therefore, this analysis may help to identify patients for interventions aimed at increasing adherence These findings will be useful to state Medicaid agencies and physicians who treat patients with schizophrenic disorders REFERENCES 1. U.S. Department of Health and Human Services. National Institute of Health. Schizophrenia. 2007 Jan; 06-3517. Available at: www.nimh.gov/health/publications/schizophrenia/ schizophrenia-booklet---2006.pdf. Accessed April 7, 2008. 2. Valenstein M, Copeland LA, Blow FC, et al. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care. 002;40(8):630-639. 3. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004;161(4):692-699. 4. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv. 2001;52(6):805-811. Poster presented at the 13th International Meeting of the International Society for Pharmacoeconomics and Outcomes Research; May 3 7, 2008; Toronto, Canada.