Comorbidity burden, healthcare resource utilization, and costs in chronic gout patients refractory to conventional urate-lowering therapy.

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis significantly impairs work productivity and daily activities. OBJECTIVES: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis. METHODS: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response (≥ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity. RESULTS: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P < .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment). LIMITATIONS: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis. CONCLUSIONS: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis.

Risks of developing psychiatric disorders in pediatric patients with psoriasis.

BACKGROUND: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. OBJECTIVE: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. METHODS: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. RESULTS: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). LIMITATIONS: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. CONCLUSIONS: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

Treatment persistence & health care costs of adult MDD patients treated with escitalopram vs. citalopram in a medicaid population.

OBJECTIVE: Compare treatment persistence and health care costs of major depressive disorder (MDD) Medicaid patients treated with escitalopram versus citalopram. DESIGN: Retrospective analysis of Medicaid administrative claims data. METHODOLOGY: Analyzed administrative claims data from the Florida Medicaid program (07/2002-06/2006) for patients ages 18-64 years with 21 inpatient claim or 2 independent medical claims for MDD. Outcomes included discontinuation and switching rates and prescription drug, medical, and total health care costs, all-cause and related to mental disorder. Contingency table analysis and survival analysis were used to compare outcomes between treatment groups, using both unadjusted analysis and multivariate analysis adjusting for baseline characteristics. RESULTS: The study included 2,650 patients initiated on escitalopram and 630 patients initiated on citalopram. Patients treated with escitalopram were less likely to discontinue the index drug (63.7% vs. 68.9%, P=0.015) or to switch to another second-generation antidepressant (14.9% vs. 18.4%, P=0.029) over the six months post-index date. Patients treated with escitalopram had $1,014 lower total health care costs (P=0.032) and $519 lower health care costs related to mental disorder (P=0.023). More than half of the total cost difference was attributable to savings in inpatient hospitalizations related to mental disorder ($571, P=0.003) and to outpatient costs ($53, P<0.001). Escitalopram therapy was also associated with $736 lower medical costs related to mental disorder (P=0.009). CONCLUSION: In the Florida Medicaid program, compared to adult MDD patients initiated on citalopram, escitalopram patients have better treatment persistence and lower total health care costs due to any cause and due to mental disorder, mostly driven by lower hospitalization costs related to mental disorder.

Increased risks of developing anxiety and depression in young patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is associated with substantial psychosocial burden and increased risks for mental health disorders. This retrospective cohort study compared the risks of developing anxiety disorders and depression and incidences of psychotropic medication use between young CD patients and matched CD-free controls. METHODS: Medical claims, prescription drug claims, enrollment, and demographic data for patients <18 years diagnosed with CD were obtained from the MarketScan database (1 January 2000-30 June 2006). Each CD patient was matched with five CD-free controls based on exact age, sex, and months of health plan enrollment. Incidence rates and risks of developing anxiety disorders and depression and psychotropic medication use in the 6 months after the index date were compared, as were risks of developing persistent anxiety or depression (receiving medical services related to a diagnosis of anxiety or depression or psychotropic therapy for >1 year). RESULTS: After adjustment for patient characteristics, the risks of developing anxiety disorders (hazard ratio (HR) [95% confidence interval (CI);[equals;2.28 [1.65-3.17]) and depression (HR [95% CI;[equals;1.74 [1.35-2.25]) after CD diagnosis were significantly greater for the CD cohort (N=2,144) than for CD-free controls (N=10,720). Patients with CD also had greater risks of developing persistent anxiety and persistent depression (HR [95% CI;[equals;4.35 [2.22-8.50] and 2.75 [1.73-4.38], respectively). CONCLUSIONS: Compared with matched CD-free controls, young patients with CD had significantly greater risks of developing anxiety disorders and depression, were more likely to receive psychotropic treatments, and had significantly greater risks of developing persistent anxiety and depression.

Compliance, persistence, healthcare resource use, and treatment costs associated with aliskiren plus ARB versus ACE inhibitor plus ARB combination therapy: in US patients with hypertension.

BACKGROUND: Evidence is currently equivocal on the added benefits of dual blockade of the renin-angiotensin-aldosterone system with the combination of either an ACE inhibitor (ACEI) plus an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) or aliskiren, the first-in-class direct renin inhibitor, plus an ARB. OBJECTIVE: To compare the compliance, persistence, healthcare resource utilization, and healthcare costs associated with aliskiren plus ARB versus ACEI plus ARB combination therapies among adult patients diagnosed with hypertension. METHODS: Patients (aged ≥18 years) initiated on either combination therapy were identified in the MarketScan Commercial and Medicare Supplemental Databases (1 July 2007 to 30 June 2008). The ARB components considered were candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan. The ACEI components included benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril. Outcomes measured during the 6-month study period included the proportion of days covered (PDC), treatment discontinuation, healthcare resource utilization, and changes in healthcare costs (study period minus 6-month baseline values). Risk-adjusted differences in outcomes between treatments and associated 95% confidence intervals (CIs) were estimated using multivariate regression models, controlling for demographics, region, co-morbidities, prescription drug use, and resource utilization during the baseline period. RESULTS: Adjusting for baseline characteristics, aliskiren plus ARB patients (n = 1395) demonstrated a significantly higher PDC (67.0% vs 54.3%; difference 12.7%; 95% CI 10.6, 14.7) and a significantly lower discontinuation rate (50.4% vs 68.6%; odds ratio 0.46; 95% CI 0.40, 0.54) than ACEI plus ARB patients (n = 16 507). Aliskiren plus ARB patients had significantly fewer all-cause hospitalizations (adjusted incidence rate ratio [IRR] 0.73; 95% CI 0.61, 0.86) and significantly fewer all-cause emergency room (ER) visits (adjusted IRR 0.72; 95% CI 0.61, 0.85) than ACEI plus ARB patients. Compared with ACEI plus ARB therapy, aliskiren plus ARB therapy was associated with significantly larger increases in prescription costs by $US264 post therapy initiation (95% CI 153, 375), but with non-significantly greater reductions in total healthcare costs by -$583 (95% CI -2409, 1242).[2008 values]. CONCLUSION: In adult hypertensive patients, treatment with aliskiren plus ARB was associated with significantly better compliance/persistence and fewer hospitalizations and ER visits compared with ACEI plus ARB therapy. Reductions in total healthcare costs were non-significantly different between patients treated with aliskiren plus ARB versus ACEI plus ARB, despite the increased prescription costs associated with aliskiren plus ARB therapy.

Economic impact of therapeutic substitution of a brand selective serotonin reuptake inhibitor with an alternative generic selective serotonin reuptake inhibitor in patients with major depressive disorder.

BACKGROUND: To reduce pharmacy costs, managed care organizations encourage therapeutic substitution from brand to a generic product. However, little is known about whether these cost-containment strategies can also potentially lower total expenditures for payers in treatment of major depressive disorder (MDD). OBJECTIVE: To compare economic outcomes of patients with MDD who were switched from a brand selective serotonin reuptake inhibitor (SSRI) to an alternative generic SSRI for nonmedical reasons versus patients who continued on the brand SSRI. METHODS: Adult MDD patients in the Ingenix Impact Database (2003-2007) were considered "switchers" if they received treatment with a brand SSRI and were later switched to an alternative generic SSRI for nonmedical reasons. Patients who remained on the brand SSRI (nonswitchers) were matched 1:1 with switchers. All-cause, mental health-related, and MDD-related rates of hospitalizations/emergency department (ED) visits and costs over 6 months were compared both descriptively and by using adjusted regression models. A subgroup analysis on patients who were switched from escitalopram (Lexapro) to an alternative generic SSRI was also performed. RESULTS: The study included 4449 matched pairs. Compared with nonswitchers, switchers had higher risk of all-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.15, 1.34, and 1.54, respectively; all p < 0.01) and higher risk-adjusted mental health-related and MDD-related medical costs ($219 and $222, respectively; both p < 0.05). Subgroup analysis on escitalopram showed similar results; switchers experienced higher risk of any-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.21, 1.41, and 1.53, respectively; all p < 0.01) and higher risk-adjusted MDD-related medical costs ($151; p < 0.05). CONCLUSIONS: Compared with patients who continued on their patented SSRIs, patients who switched to a generic SSRI incurred more resource use of hospitalizations/ED visits and higher MDD-related health-care costs. The effects of therapeutic substitution should be carefully examined, because use of generic alternatives may not be a cost-saving strategy when total health-care costs are considered.

Effects of adalimumab versus placebo on risk of symptom worsening in psoriasis and subsequent impacts on health-related quality-of-life: analysis of pooled data from two randomized, double-blind, placebo-controlled, multicentre clinical trials.

BACKGROUND: Rates and impacts of worsening symptoms in patients with psoriasis have not been well characterized. OBJECTIVES: To assess the risk of clinically relevant worsening of psoriasis symptoms in patients treated with adalimumab versus placebo and to determine the health-related quality-of-life (HRQOL) impacts of such worsening. METHODS: The cumulative incidence of worsening was compared for adalimumab (40 mg every other week following an 80 mg induction dose) versus placebo using data from two phase III randomized, placebo-controlled trials (CHAMPION and REVEAL). Clinically relevant worsening of psoriasis was defined as a follow-up visit with a ≥25% increase in the Psoriasis Area and Severity Index (PASI) from baseline or a ≥5-unit increase in the Dermatology Life Quality Index from baseline during the initial 16-week double-blind treatment periods. Patients with versus without worsening were compared in terms of pain, work productivity and activity impairment (WPAI) and the mental and physical component summary (MCS and PCS) scores of the Short-Form 36 Health Survey. A subgroup analysis was performed for patients with PASI 10-20 at baseline. RESULTS: The 17-week risk of clinically relevant worsening was 37.0% (95% CI 26.1, 46.3) for placebo (n = 445) and 4.2% (95% CI 2.0, 6.3) for adalimumab-treated patients (n = 914) [p < 0.0001]. Patients with versus without worsening experienced substantially increased pain, increased WPAI and greater impairment in MCS and PCS. Results were similar for patients with PASI 10-20 at baseline. LIMITATIONS: The short study duration may not reflect long-term outcomes. CONCLUSION: Clinically relevant worsening of psoriasis symptoms was associated with substantial worsening of HRQOL. Adalimumab treatment was associated with a substantially reduced risk of clinically relevant worsening.

Estimating the effect of medication adherence on health outcomes among patients with type 2 diabetes--an application of marginal structural models.

OBJECTIVE: We applied marginal structural models (MSMs) to estimate the effects of medication adherence with hypoglycemics on reducing the risk of microvascular complications in type 2 diabetic patients. METHODS: A retrospective longitudinal cohort study for type 2 diabetes patients was conducted using the California Medicaid claims database (1995-2002). Medication adherence and multiple time-varying confounders were measured quarterly over a maximum of 7.5 years follow-up. Cox regression models and MSMs results on the effect of compliance were compared. RESULTS: Of 4708 eligible patients, 2644 (56.2%) experienced microvascular complications during the follow-up period. After controlling for baseline covariates, standard Cox models estimated that adherence was associated with increased risk of complication with hazard ratio (HR) of 1.09 (95% confidence interval (CI): 1.00, 1.18). With adjustment of time-varying confounders as exogenous variables, the HR was 0.96 (0.88, 1.04). Using the MSM technique, the HR was 0.76 (95% bootstrap CI: 0.60, 0.92), indicating a significant benefit of medication adherence with hypoglycemics on the reduction of microvascular complications. This result contrasts with the negative results obtained in the hazard model, and is more consistent with prior clinical trial results CONCLUSION: Unlike conventional models, MSMs estimated that higher medication adherence may result in reduced risk of microvascular complications among patients with type 2 diabetes.

The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: a randomized clinical trial.

BACKGROUND: Psoriasis is associated with health-related quality-of-life impairment and depression. OBJECTIVE: We sought to determine the effect of adalimumab on depression symptoms in patients with psoriasis. METHODS: Patients with moderate to severe psoriasis in a randomized, placebo-controlled, double-blind clinical trial were assessed for depression symptoms at baseline and week 12 or early termination (ET) using the Zung Self-rating Depression Scale (ZDS). The effects of adalimumab (40 mg every other week) versus placebo on ZDS score at week 12/ET were assessed using analysis of covariance. Relationships between ZDS and the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index, and the Short Form 36 Health Survey were assessed using Pearson correlations. Changes in ZDS score were compared for patients with and without a 75% or greater reduction in baseline PASI score. RESULTS: Compared with the placebo group (n = 52), the adalimumab group (n = 44) experienced an additional 6-point reduction in ZDS score (95% confidence interval: 2.5-9.5; P < .001) by week 12/ET. Depression improvement was correlated with improvement in PASI (r = 0.5; P < .0001) and Dermatology Life Quality Index (r = 0.5; P < .0001). Greater ZDS score improvement was observed at week 12/ET in responders with a 75% or greater reduction in baseline PASI score than in nonresponders (10.6 [SD = 9.4] vs 1.4 [SD = 9.6]; P < .001). LIMITATIONS: This analysis cannot distinguish whether adalimumab has a direct or indirect effect on depression. CONCLUSIONS: Adalimumab treatment reduced psoriasis symptoms, reduced depression symptoms, and improved health-related quality of life in patients with moderate to severe psoriasis.

Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: comparison of adverse event-free response days in the CHAMPION trial.

BACKGROUND: The Comparative Study of Humira versus Methotrexate (MTX) versus Placebo in Psoriasis Patients (CHAMPION) demonstrated superior efficacy of biologic over conventional systemic immunosuppressant therapy in psoriasis. OBJECTIVE: We sought to compare the risk-benefit profile of adalimumab (ADA), MTX, and placebo using data from CHAMPION. METHODS: Patients randomized to ADA (n = 107), MTX (n = 110), or placebo (n = 53) were followed up for 16 weeks. Response (≥75% improvement in Psoriasis Area and Severity Index), days free of adverse events (AEs), moderate to severe AEs, infection-related AEs, and study drug-related AEs were analyzed. RESULTS: ADA treatment was associated with substantially more days (SD) of AE-free response compared with MTX or placebo treatment, respectively: 36.9 (31.1) versus 8.3 (15.9) or 6.7 (18.1) days of response free of any AEs, 43.8 (31.9) versus 11.1 (19.9) or 7.9 (19.9) days of response free of moderate to severe AEs, 48.5 (29.2) versus 12.4 (21.7) or 9.2 (21.8) days of response free of infection-related AEs, and 44.6 (31.4) versus 11.8 (21.1) or 10.0 (24.0) days free of study drug-related AEs (all P < .0001 for ADA vs MTX or placebo). LIMITATIONS: This clinical trial-based analysis may not have captured the full spectrum of AEs in the actual clinical setting. The short (16-week) duration of the trial limited the ability to capture some important but uncommon AEs associated with long-term ADA or MTX use. CONCLUSION: With 4 times as many AE-free response days, ADA demonstrated a superior benefit-risk profile.

Impact of adalimumab on symptoms of psoriatic arthritis in patients with moderate to severe psoriasis: a pooled analysis of randomized clinical trials.

BACKGROUND: Psoriatic arthritis often affects patients with psoriasis. OBJECTIVE: To examine the effect of adalimumab on psoriatic arthritis in patients with moderate to severe psoriasis. METHODS: Data from patients with psoriasis and a reported history of comorbid psoriatic arthritis in 3 randomized, placebo-controlled psoriasis trials of adalimumab were analyzed. RESULTS: Adalimumab (n = 274) reduced the risk of psoriatic arthropathy adverse events by 75% versus placebo (1.1 vs. 4.8%; p = 0.025). Psoriasis/psoriatic arthritis-related pain was significantly reduced (-31.3 vs. -5.6 visual analog scale units; p < 0.0001). At week 16, adalimumab-treated patients were more likely to respond (56.9 vs. 4.5%; p < 0.001) and responded for a greater percentage of follow-up time (39.3 vs. 2.9%; p< 0.0001) than placebo-treated patients (regression model for PASI 75 and ACR 20 responses). CONCLUSION: Adalimumab treatment of moderate to severe psoriasis reduced symptoms of comorbid psoriatic arthritis.

High prevalence of potential drug-drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice.

BACKGROUND: Methotrexate (MTX) and cyclosporine (CYC) may adversely interact with common medications in patients with psoriasis. OBJECTIVE: Our purpose was to investigate the prevalence and outcomes of MTX/CYC polypharmacy. METHODS: We evaluated rates of events that may be associated with drug-related toxicity, health care resource utilization and costs for patients with psoriasis in the Ingenix(R) Impact National Managed Care Database (1999-2007) who were exposed or not exposed to potential drug-drug interactions. RESULTS: Among 4,583 (57.6%) exposed and 3,372 (42.4%) nonexposed patients, nonsteroidal anti-inflammatory drugs and antibiotics were the most common drugs with potential interactions. The exposed patients had significantly greater risks of developing renal [adjusted odds ratio (OR): 2.58; p = 0.0145], gastrointestinal (OR: 1.36; p = 0.0197) and pulmonary events (OR: 1.20; p = 0.0470), and significantly greater health care resource utilization (e.g. OR for inpatient and emergency department visits: 1.47; p < 0.0001) and costs (adjusted incremental cost: USD 1,722; p < 0.0001). CONCLUSIONS: MTX/CYC polypharmacy is prevalent in patients with psoriasis and associated with significant risks.

Clinical outcomes and medical care costs among medicare beneficiaries receiving therapy for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a common disorder with multiple options for treatment, ranging from medical interventions, surgical revascularization, and endovascular therapy. Despite the explosive advances in endovascular therapy, cost-effective methods of care have not been well defined. We analyze therapeutic strategies, outcomes, and medical cost of treatment among Medicare patients with PAD. METHODS AND RESULTS: Patients who underwent therapy for PAD were identified from a 5% random sample of Medicare beneficiaries from Medicare Standard Analytic Files for the period 1999-2005. Clinical outcomes (death, amputation, new clinical symptoms related to PAD) and direct medical costs were examined by chosen revascularization options (endovascular, surgical, and combinations). One-year PAD prevalence increased steadily from 8.2% in 1999 to 9.5% in 2005. The risk-adjusted time to first post-treatment clinical outcome was lowest in those treated with "percutaneous transluminal angioplasty (PTA) or atherectomy and stents" (HR, 0.829; 95% CI, 0.793-0.865; p < 0.001) and stents only (HR, 0.904; 95% CI, 0.848-0.963; p = 0.002) compared with PTA alone. The lowest per patient risk-adjusted costs during the quarter of the first observed treatment were associated with "PTA and stents" ($15,197), and stents only ($15,867). Risk-adjusted costs for surgical procedures (bypass and endarterectomy) were $27,021 during the same period. Diabetes was present in 61.7% of the PAD population and was associated with higher risks of clinical events and higher medical costs compared with PAD patients without diabetes. CONCLUSION: The clinical and economic burden of PAD in the Medicare population is substantial, and the interventions used to treat PAD are associated with differences in clinical and economic outcomes. Prospective cost-effectiveness analyses should be included in future PAD therapy trials to inform payers and providers of the relative value of available treatment options.

Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study.

BACKGROUND & AIMS: We determined the effects of adalimumab maintenance treatment on the risks of hospitalization and surgery in Crohn's disease (CD). METHODS: A total of 778 patients with CD were randomized to placebo, adalimumab 40 mg every other week or adalimumab 40 mg weekly, all after an 80-mg/40-mg adalimumab induction regimen. All-cause and CD-related hospitalizations and major CD-related surgeries were compared between the placebo and adalimumab groups (every other week, weekly, and both combined) using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Both 3- and 12-month hospitalization risks were significantly lower for patients who received adalimumab. Hazard ratios for all-cause hospitalization were 0.45, 0.36, and 0.40 for the adalimumab every other week, weekly, and combined groups, respectively (all P < .01 vs placebo). Hazard ratios for CD-related hospitalization were 0.50, 0.34, and 0.42, respectively (all P < .05). Cox model estimates demonstrated adalimumab every other week and weekly maintenance therapies were associated with 52% and 60% relative reductions in 12-month, all-cause hospitalization risk, and 48% and 64% reductions in 12-month risk of CD-related hospitalization. The combined adalimumab group was associated with 56% reductions in both all-cause and CD-related hospitalization risks. Fewer CD-related surgeries occurred in the adalimumab every other week, weekly, and combined groups compared with placebo (0.4, 0.8, and 0.6 vs 3.8 per 100 patients; all P < .05). CONCLUSIONS: Patients with moderate-to-severe CD treated with adalimumab had lower 1-year risks of hospitalization and surgery than placebo patients.

Comparison of two adalimumab treatment schedule strategies for moderate-to-severe Crohn's disease: results from the CHARM trial.

OBJECTIVES: To compare outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with reinitiation of adalimumab (in the event of clinical deterioration) for patients with moderate-to-severe Crohn's disease (CD) who participated in the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM). METHODS: In the CHARM trial, all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2, respectively. In total, 778 patients were randomized at week 4 to one of three groups: (1) placebo after initial induction doses (followed by reinitiation of adalimumab therapy); (2) continuous maintenance treatment with adalimumab 40 mg every other week (e.o.w.); and (3) continuous maintenance treatment with adalimumab 40 mg every week. At/after week 12, patients receiving placebo with flare or non-response could reinitiate open-label adalimumab 40 mg e.o.w., and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w. Patients in all groups could switch to weekly therapy with continued flare/non-response. In the previously published primary analysis, results for only those patients who had responded at week 4 (decrease in Crohn's Disease Activity Index (CDAI) of > or = 70 points, referred to as "randomized responders") and remained on blinded therapy were analyzed. In this analysis, data from all randomized patients were analyzed based on original randomized treatment using an intention-to-treat analysis, regardless of whether they subsequently switched to open-label therapy. Disease activity, clinical remission, number of flares, Inflammatory Bowel Disease Questionnaire (IBDQ) score, number of CD-related surgeries, and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups. RESULTS: Results for all outcome measures were superior for both continuous groups compared with the induction only/reinitiation group. On the basis of median CDAI and IBDQ results, patients in both continuous treatment groups achieved statistically significantly greater improvements vs. the induction only/reinitiation group (P < 0.05). At week 56, a significantly greater percentage of patients who had received continuous adalimumab (51% for e.o.w. and 49% for weekly) were in clinical remission vs. the induction only/reinitiation group (38%, P < 0.05). Continuous adalimumab therapy was also associated with fewer flares and fewer CD-related surgeries (P < 0.05). Patients in both continuous adalimumab groups had significantly lower risks of CD-related and all-cause hospitalizations than did patients in the induction only/reinitiation group (P < 0.05). CONCLUSIONS: For patients with active CD, continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by reinitiation of adalimumab with clinical deterioration for maintenance of clinical remission, improved quality-of life outcomes, reduced flares, and a decrease in number of surgeries and risk of hospitalization.

Resource utilization and costs of schizophrenia patients treated with olanzapine versus quetiapine in a Medicaid population.

OBJECTIVE: Compare annual health-care costs and resource utilization associated with olanzapine versus quetiapine for treating schizophrenia in a Medicaid population. METHODS: Adult schizophrenia patients were selected from deidentified Pennsylvania Medicaid claims database (1999­2003). Included patients were continuously enrolled and initiated with olanzapine or quetiapine monotherapy after a 90-day washout period. Treatment costs were calculated for 1-year post-therapy initiation and inflation adjusted to year 2003. To control for selection bias, olanzapine and quetiapine patients were 1:1 matched using an optimal matching algorithm on propensity score, which was generated using logistic regression controlling for demographics, prior drug therapy, utilization, and costs. Treatment costs for the matched cohorts were compared directly, as well as using a difference-in-difference analysis. RESULTS: A total of 6929 patients treated with olanzapine and 2321 with quetiapine met inclusion criteria. Quetiapine patients appeared more severe at baseline. After propensity score matching, 2321 patient pairs had similar baseline characteristics, including total costs. Compared with matched quetiapine patients, for the 1-year postindex period, olanzapine patients had similar drug costs ($6131 vs. $6014, P = 0.326), lower medical costs ($9897 vs. $11,218, P = 0.0128), and lower total health-care costs ($16,028 vs. $17,232, P = 0.0279). Lower psychiatric hospitalization costs account for most of the total cost difference. Difference-in-difference regression analysis confirmed olanzapine's economic advantage. Further adjusting for baseline variations, the total cost advantage of olanzapine patients was $962 (P = 0.032), and was mostly because of reduced psychiatric hospitalization costs of $992 (P = 0.004). CONCLUSION: Schizophrenia patients treated with olanzapine had lower total costs than quetiapine patients, mostly attributable to reductions in psychiatric hospitalization costs.

Cost utility of adalimumab versus infliximab maintenance therapies in the United States for moderately to severely active Crohn's disease.

OBJECTIVE: To determine and compare the cost utilities of the tumour necrosis factor (TNF) antagonists adalimumab and infliximab as maintenance therapies for patients in the US with moderately to severely active Crohn's disease. METHODS: Maintenance regimens of adalimumab (40 mg every other week) and infliximab (5 mg/kg) were compared using primary data from the CHARM and published data from the ACCENT I clinical trials. Differences in study samples were minimized by matching and weighting baseline characteristics (Crohn's Disease Activity Index score, age and sex) between the patient groups using the primary clinical trial data. Utilization data were estimated from trial data. Unit costs of TNF antagonists (year 2007 values), hospitalizations (year 2006 values), and other medical costs (year 2006 values) were derived from a systematic literature search. Standard gamble-calculated primary data were used to derive health-utility estimates. Data were analysed in a cost-utility framework from a private payer perspective over a 56-week time horizon. Univariate and probabilistic sensitivity analyses were used to explore uncertainty related to the base-case cost-utility analysis. Given the time horizon, costs and effects were not discounted. RESULTS: Adalimumab- and infliximab-treated patients were in remission for 47.2% and 37.1% of the 56-week period, respectively. Hospital admissions were 34-40% lower for adalimumab than for infliximab, based on the model and observed data, respectively. Patients treated with adalimumab accrued greater expected QALYs (0.014; 95% CI 0.000, 0.022) and lower costs (-$US4852; 95% CI -6758, 491) in the first year of therapy than patients treated with infliximab. Compared with infliximab maintenance therapy, adalimumab had lower drug and administration costs, less drug waste, and lower hospitalization rates. Univariate and multivariate probabilistic sensitivity analyses suggested that these results were robust. CONCLUSIONS: This analysis suggests that adalimumab maintenance therapy is a dominant strategy versus infliximab maintenance therapy for patients with moderate to severe Crohn's disease. Adalimumab appeared more effective and less costly than infliximab.

Treatment persistence, healthcare utilisation and costs in adult patients with major depressive disorder: a comparison between escitalopram and other SSRI/SNRIs.

OBJECTIVE: Compare treatment persistence, healthcare utilisation and costs for patients treated with escitalopram versus other SSRI/SNRIs in a real-world setting. METHODS: Patients with a diagnosis for major depressive disorder (MDD) and at least one prescription for an SSRI or SNRI were identified from the Ingenix Impact Database (2002-2005). The baseline and study observation periods were defined as the 6 months before and after the index date (first date for an SSRI /SNRI pharmacy claim). Comparisons were made between patients initiated on escitalopram versus other SSRI/SNRIs using descriptive statistics and multivariate regressions. RESULTS: Escitalopram patients (n=10,465) had better treatment persistence compared to patients initiated on other SSRI/SNRIs (n=28,310): the hazard ratio of all discontinuation was 0.96 (95% confidence interval [CI]=0.94-0.99) for the escitalopram therapy (p=0.003), and the hazard ratio of switching to another second-generation antidepressant was 0.91 (95% CI=0.87-0.94) for the escitalopram therapy (p<0.001). Escitalopram patients also had fewer inpatient service and emergency room visits. Adjusted average total all-cause healthcare costs and inpatient services costs were $839 and $405 lower in the escitalopram group (both p<0.05). CONCLUSIONS: Escitalopram may be associated with lower healthcare utilisation and costs among adult MDD patients compared to other SSRI/SNRIs.

Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn's disease: patient-reported outcomes of the CHARM trial.

OBJECTIVES: We evaluated the effects of adalimumab maintenance therapy on health-related quality of life (HRQOL) in patients with moderate to severe Crohn's disease. METHODS: In a Phase III, randomized, double-blind clinical trial (CHARM) of moderate to severe Crohn's disease patients, HRQOL outcomes were compared between the adalimumab maintenance treatment groups (every other week and weekly injection) and the adalimumab induction-only group. The Zung Self-Rating Depression Scale, functional assessment of chronic illness therapy (FACIT)-Fatigue, visual analog pain scales, Inflammatory Bowel Disease questionnaire (IBDQ), and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) were analyzed for 499 randomized responders (a decrease of > or =70 points from baseline in the Crohn's Disease Activity Index [CDAI]) at baseline and weeks 4, 12, 26, and 56. RESULTS: CHARM patients' HRQOL was substantially impaired at baseline. Following a 4-week adalimumab induction therapy, patients experienced statistically significant improvements in all HRQOL measures (P < 0.0001). Compared with patients who were assigned to placebo after induction therapy, patients who continued adalimumab at 40 mg every other week maintenance therapy reported less depression (P < 0.01), fewer fatigue symptoms (P < 0.001), greater improvements in the IBDQ (P < 0.05), greater SF-36 physical component summary scores (P < 0.05), and less abdominal pain (P < 0.05) from weeks 12 to 56. They also had greater SF-36 mental component summary scores at week 56 (P < 0.05). Patients who continued adalimumab at 40-mg weekly maintenance therapy reported less depression and fewer fatigue symptoms at week 56, greater improvement in IBDQ, and less abdominal pain from weeks 12 to 56 (all P < 0.05 vs. placebo). CONCLUSIONS: Adalimumab maintenance therapy provided sustained improvements in HRQOL for patients with moderate to severe Crohn's disease through week 56.