Shiraz R. Gupta

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). Reweighting 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 frombaseline 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.

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.

Economic burden of psoriasis compared to the general population and stratified by disease severity.

Abstract Objective: To evaluate health care utilization and costs for patients with psoriasis vs. the general population and by psoriasis severity. Research design and methods: Claims data were analyzed for adult patients with ≥1 diagnosis of psoriasis and continuous enrollment during the year of 2003 (case sample). A control sample was matched 2:1 on baseline demographic characteristics to the case sample. Case samples were further stratified by psoriasis severity based on treatment patterns. Outcomes were compared descriptively and by a multivariate two-part model to evaluate differences between the case vs. control groups and by psoriasis severity. Main outcome measures: Outcomes included health care resource utilization and health care costs. Results: A total of 56,528 patients with psoriasis met the inclusion criteria. Patients with psoriasis had significantly greater total health care resource utilization, total medical resource utilization, and total drug utilization vs. the control sample (p < 0.0001). Compared with control patients, patients with psoriasis had significantly greater total health care costs (

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

5529 vs.

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

3509), including greater medical costs (

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

3925 vs.

Effects of Adalimumab versus Placebo on Risk of Symptom Worsening in Psoriasis and Subsequent Impacts on Health-Related Quality-of-Life

2687) and drug costs (

Cost analysis of divalproex sodium extended-release compared to valproic acid in the treatment of bipolar disorder

1604 vs.

Monitoring of pharmacy staffing, workload, and productivity in community hospitals

822; all p < 0.0001). Patients with moderate to severe psoriasis (n = 5248) had greater total health care costs vs. patients with mild psoriasis (n = 51,280) (

Association between hospital size and pharmacy department productivity

10,593 vs.