A longitudinal analysis of costs associated with change in disease activity in systemic lupus erythematosus.

OBJECTIVES: To estimate the economic consequences of changes in disease activity on healthcare resource utilization (HRU) and costs. METHODS: A retrospective longitudinal study of systemic lupus erythematosus (SLE) patients receiving care in a regional integrated health delivery system in the US from 01/2004 through 03/2011 was conducted using electronic health records, medical chart reviews, and claims. Eligible patients were ≥18 years old, with ≥1 rheumatologist-confirmed SLE diagnosis and ≥1 eligible rheumatology encounter. Patients were continuously enrolled ≥90 days before and ≥30 days after the encounters. Charts were manually reviewed to estimate SLEDAI scores. Average unit costs of each medical procedure, facility use, and prescription were estimated from a payer perspective (2011 USD) using a managed care claims database. HRU and costs were calculated for the 30-day period surrounding every SLEDAI score date (10 days before and 19 after). Relationships between HRU/costs and SLEDAI scores were estimated using mixed-effect models. RESULTS: Overall, 178 SLE patients were included; mean age was 50.6 years, 91% were female, and 95.5% Caucasian. Patients had a total of 1343 encounters with SLEDAI scores over an average period of 1035 days. Reductions of SLEDAI scores were associated with reductions in HRU and costs. SLEDAI score reductions of 4-points were associated with reductions of 10% HRU and 14% costs over a 30-day period; reductions of 8-points had associated reductions of 19% HRU and 26% costs; and reductions of 10-points had associated reductions of 23% HRU and 31% costs. Annualized, changes in SLEDAI scores are associated with changes of $2485 (SLEDAI score change: 10-6), $4624 (10-2), and $5579 (10-0), respectively. CONCLUSION: Reductions in disease activity were associated with substantial reductions of HRU and costs. LIMITATIONS: Only short-term effects of disease activity change were investigated, disregarding other potential benefits of low disease activity on long-term organ damage prevention or comorbidities.

Monitoring and switching patterns of patients with chronic myeloid leukemia treated with imatinib in community settings: a chart review analysis.

OBJECTIVES: Monitoring treatment response is an integral part of chronic myeloid leukemia (CML) treatment. The guidelines recommend regular monitoring using standard methods (e.g., real-time quantitative polymerase chain reaction based on the international scale for molecular response) and treatment adjustment when failure is detected among patients treated with imatinib. The objective of this study was to assess the real-world monitoring and therapy adjustment in this patient population in the US. METHODS: Twenty-nine physicians from community practices across the US participated in an online chart review. Adult patients with chronic phase CML who initiated imatinib as first-line therapy during 2006-2010 were selected. Information was collected up to 36 months after imatinib initiation, including response monitoring, response status, and therapy adjustment upon treatment failure. RESULTS: The study included 297 eligible patients. By 18 months, 47% of patients had received cytogenetic response assessment continuously as recommended by the guidelines. The corresponding proportion was 39% for continuous molecular response assessment. Among patients who experienced treatment failure by 18 months, only 14%-38% of patients switched to a second-generation tyrosine kinase inhibitor as recommended by the National Comprehensive Cancer Network and the European Leukemia Net guidelines. LIMITATIONS: Major limitations included limited generalizability and the inability to accurately assess molecular response due to the variations in testing methods during the study period. CONCLUSIONS: Based on the guidelines, the rates of treatment monitoring and switching upon failure were low, demonstrating the need for improvement in CML care in community settings in the US.

Comparative effectiveness without head-to-head trials: a method for matching-adjusted indirect comparisons applied to psoriasis treatment with adalimumab or etanercept.

The absence of head-to-head trials is a common challenge in comparative effectiveness research and health technology assessment. Indirect cross-trial treatment comparisons are possible, but can be biased by cross-trial differences in patient characteristics. Using only published aggregate data, adjustment for such biases may be impossible. Although individual patient data (IPD) would permit adjustment, they are rarely available for all trials. However, many researchers have the opportunity to access IPD for trials of one treatment, a new drug for example, but only aggregate data for trials of comparator treatments. We propose a method that leverages all available data in this setting by adjusting average patient characteristics in trials with IPD to match those reported for trials without IPD. Treatment outcomes, including continuous, categorical and censored time-to-event outcomes, can then be compared across balanced trial populations. The proposed method is illustrated by a comparison of adalimumab and etanercept for the treatment of psoriasis. IPD from trials of adalimumab versus placebo (n = 1025) were re-weighted to match the average baseline characteristics reported for a trial of etanercept versus placebo (n = 330). Re-weighting was based on the estimated propensity of enrolment in the adalimumab versus etanercept trials. Before matching, patients in the adalimumab trials had lower mean age, greater prevalence of psoriatic arthritis, less prior use of systemic treatment or phototherapy, and a smaller mean percentage of body surface area affected than patients in the etanercept trial. After matching, these and all other available baseline characteristics were well balanced across trials. Symptom improvements of ≥75% and ≥90% (as measured by the Psoriasis Area and Severity Index [PASI] score at week 12) were experienced by an additional 17.2% and 14.8% of adalimumab-treated patients compared with the matched etanercept-treated patients (respectively, both p < 0.001). Mean percentage PASI score improvements from baseline were also greater for adalimumab than for etanercept at weeks 4, 8 and 12 (all p < 0.05). Matching adjustment ensured that this indirect comparison was not biased by differences in mean baseline characteristics across trials, supporting the conclusion that adalimumab was associated with significantly greater symptom reduction than etanercept for the treatment of moderate to severe psoriasis.

Comparison of health care use and costs in newly diagnosed and established patients with fibromyalgia.

UNLABELLED: In 2004, the American Pain Society (APS) issued evidence-based fibromyalgia treatment recommendations. The objective of this claims database analysis is to describe prescription and medical use in patients with newly diagnosed and established fibromyalgia. Privately insured patients with 2+ myalgia/myositis claims (1999 to 2005) were categorized as newly diagnosed or established; this dichotomy involves comparisons between prediagnosis (S1) and postdiagnosis (S2) stages in the newly diagnosed and between newly diagnosed (S2) and established patients (S3). Use of APS guideline medications increased across stages: selective serotonin reuptake inhibitors (SSRIs) (S1, S2, S3: 20.6%, 22.9%, 25.3%), serotonin norepinephrine reuptake inhibitors (SNRIs) (4.5%, 6.4%, 8.9%), pregabalin/gabapentin (5.4%, 7.4%, 8.8%), benzodiazepines (19.0%, 21.1%, 24.2%), non-benzodiazepine sedatives (9.1%, 11.5%, 13.7%) (all P < .0001), and opioids (39.5%, 43.3%, 43.9%; S1 vs S2, P < .0001; S2 vs S3, P = .2835). Use of multiple therapeutic classes also increased across stages: 3+ classes (7.1%, 9.6%, 11.8%) (all P < .0001). Office visits to providers increased, on average, after diagnosis: primary care (70.9%, 78.3%, 76.3%; all P < .0001), chiropractors (28.8%, 51.1%, 53.3%; all P < .0001), rheumatologists (4.2%, 9.9%, 10.5%; S1 vs S2, P < .0001; S2 vs S3, P = .0595), mental health (6.4%, 7.3%, 8.3%; S1 vs S2, P < .0001, S2 vs S3, P = .0003). Average health care costs rose after diagnosis in the newly diagnosed group (S1: $6555 vs S2: $8654, P < .0001). PERSPECTIVE: This paper investigates prescription drug and medical care use with respect to stages of fibromyalgia diagnosis. Established fibromyalgia patients use more medical resources and have higher rates of concomitant medication use than newly diagnosed fibromyalgia patients. Findings can help educate providers regarding optimal drug treatment patterns in this population.

Frequency, risk, and cost of gout-related episodes among the elderly: does serum uric acid level matter?

OBJECTIVE: We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly. METHODS: Data were extracted from the Integrated Healthcare Information Services claims database (1999-2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode. RESULTS: Elderly patients with gout (n = 2237) with high (6-8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7-2.6; OR 3.4, 95% CI 2.6-4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001). CONCLUSION: Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.

Utilization pattern of etanercept and its cost implications in moderate to severe psoriasis in a managed care population.

OBJECTIVE: To describe the utilization patterns, particularly dosage-escalation patterns, and economic implications of etanercept in the treatment of moderate to severe psoriasis in a real-world setting. METHODS: Patients with psoriasis receiving etanercept were identified from the Integrated Health Care Information Services database and were observed for 12 months or until etanercept discontinuation (defined as gap of >60 days between prescriptions). Patients were excluded if they had other autoimmune conditions or received TNF antagonists within 6 months of the index date. Ratios of patients with dosage increase to total sample were calculated. Among patients continuing treatment for 1 year, etanercept dosage and drug costs (measured by average wholesale price) were compared for patients with and without dosage increase using the Wilcoxon signed rank test. RESULTS: 55.2% of patients discontinued during the study year; 51.6% of patients initiated at 100 mg/week; and 34.8% who initiated at 50 mg/week required dosage increases. Among patients continuously treated for 1 year, dosage increase resulted in incremental annual drug costs of $8,440 and $9,313 for 100 and 50 mg/week, respectively (both p < 0.0001). The annual dosage of etanercept in excess of the labeled amount translated into $2,040 and $3,032 greater etanercept costs per patient in the 100 and 50 mg/week groups, respectively. CONCLUSION: In this analysis, 33-50% of patients with psoriasis required dosage increases during their first year of etanercept therapy, resulting in increased annual treatment costs as compared with expected costs imputed from label indications. Because of patient selection criteria, the findings may not be representative of the entire population of patients with psoriasis.

Disease-related and all-cause health care costs of elderly patients with gout.

BACKGROUND: Gout is a common cause of inflammatory arthritis in the United States, and its prevalence has increased in recent decades, especially among older adults. Older adults with gout are of particular interest because they tend to experience higher rates of tophi, an advanced stage of gout, than do younger patients. OBJECTIVE: For older adults with gout to (1) assess health care utilization and costs from a third-party payer perspective; (2) evaluate health care costs related to tophi; and (3) explore the relationship between elevated serum uric acid (UA) level, an indicator of disease control, and health care utilization. METHODS: Data were extracted from the Integrated Healthcare Information Services (IHCIS) claims database (1999-2005), which includes approximately 40 private health plans in the United States for approximately 13 million beneficiaries, about 4% of whom are aged 65 years or older. Patients were included in the study if they: (1) had 2 diagnoses of gout (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1 gout-related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date (study index date); and (3) had 1 year of continuous eligibility both before and after the study index date. A comparison sample of elderly members without gout was selected using a 1:1 match to gout patients based on age, gender, and geographic region. Individuals in the comparison group also had 1 year of continuous eligibility both before and after the study index date, defined as the same index date as the respective matched gout patient. Patients with possible tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x (274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear; 274.89 = gout with other specified manifestations) during the 12-month study period following the study index date. Additionally, a subgroup of gout patients with at least 1 serum UA measure was selected. Patients were divided into 3 groups according to their serum UA level on the earliest test date (serum UA index date): low (< 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high (> or = 9 mg per dL). Health care utilization was categorized into inpatient services, outpatient services, emergency room services, other medical services, and use of prescription drugs. Medical services were classified by the place of service indicated in the claim. Medical services costs and pharmacy costs were defined as the amount paid to the provider plus member cost share (e.g., deductible, copayment). Two types of costs were assessed in the analysis: total all-cause health care costs and gout-related costs, defined as costs associated with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code 274.xx). Differences in total all-cause health care costs were calculated by comparing (1) gout patients and gout-free members during the 12-month period following the study index date; (2) gout patients with and without tophi during the 12-month period following the study index date; and (3) gout patients across the 3 serum UA categories during the 12-month period following the serum UA index date. Multivariate regression analyses were used to control for patients' baseline demographics, prior comorbidities indicated by the Deyo-Charlson Comorbidity Index, and number of medications used during the 12 months prior to the study index date. RESULTS: Over the 7 years of claims data through 2005, there were 11,935 gout patients aged 65 years or older. The sample had an average age of 71.4 years and was predominantly male (73.5%). In the 12 months following the study index date, the mean unadjusted per-patient gout-related health care cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total all-cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted total 12-month all-cause health care cost for the gout-free members was $9,219 (SD $20,186). After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients and gout-free members was $3,038 (P < 0.001). A diagnosis suggesting possible tophi was found in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment for comorbidities, the difference in total 12-month all-cause health care costs between gout patients with and without tophi was $5,501 (P < 0.001), and the difference in total adjusted 12-month gout-related costs between patients with and without tophi was $1,710 (P < 0.001). Among the 2,237 (18.7%) patients with at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a moderate-high serum UA level, and 19.3% had a very high serum UA level. For patients with low, moderate-high, and very high serum UA levels, regression-adjusted gout-related costs in the 12 months following the serum UA index date represented, respectively, 2.9%, 2.7%, and 3.9% of total regression-adjusted health care costs. The group with a very high serum UA level had significantly higher regression-adjusted total 12-month all-cause health care costs and gout-related costs compared with those with a low serum UA level ($3,103 and $276 higher, respectively). CONCLUSIONS: Elderly patients with a diagnosis of gout have higher all-cause health care utilization and costs compared with matched elderly patients without a diagnosis of gout. Gout-related costs represent about 6% of total health care costs in elderly patients with gout. Very high serum UA levels (i.e., > or = 9 mg per dL) and diagnoses suggesting possible tophi are associated with increased utilization and costs in elderly gout patients.