Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model.

BACKGROUND: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. MATERIALS AND METHODS: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. RESULTS: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. CONCLUSION: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.

Health Care Resource Utilization and Costs for Metastatic Breast Cancer Patients Newly Treated with Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Agents.

INTRODUCTION: HER2-positive metastatic breast cancer (mBC) is an incurable disease associated with years of chronic therapy and excess cost. HER2-targeted therapies have shown survival benefit for early-stage and mBC; however, the economic impact of these therapies has not been fully assessed. We evaluated health care resource use (HCRU) and costs of mBC patients treated with HER2-targeted therapy. METHODS: This was a retrospective cohort study using the IQVIA Real-World Data Adjudicated Claims Database (July 1, 2014 to July 31, 2019). Female patients aged ≥18 years with mBC who initiated HER2-targeted therapy in the prior year were identified. The index date was the initiation date of the HER2-targeted agent, after which patients were required to have ≥12 months of follow-up. Annual and cumulative all-cause and BC-related costs (2019 USD) and annual BC-related HCRU were computed in years 1, 2, and 3 following the index date. RESULTS: Following the initiation of HER2-targeted therapy, the mean annual total all-cause costs per patient in years 1 (n = 423), 2 (n = 357), and 3 (n = 166) were $320,892 (SD: $224,343), $235,159 (SD: $185,287), and $226,254 (SD: $197,901), respectively. The mean annual total BC-related costs were $240,048 (SD: $151,230), $175,631 (SD: $148,058), and $165,506 (SD: $159,374) in years 1, 2, and 3, respectively. A major portion of BC-related costs were costs associated with HER2-targeted treatment. The 3-year cumulative all-cause and BC-related total costs were $769,573 (SD: $456,920) and $624,455 (SD: $401,319), respectively. CONCLUSION: Treatment of HER2-positive mBC is a substantial economic burden. A potential approach to minimizing cost and HCRU is to prevent recurrence.

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

Quality adjusted life year gains associated with administration of recombinant tissue-type plasminogen activator for treatment of acute ischemic stroke: 1998-2011.

BACKGROUND: Intravenous recombinant tissue-type plasminogen activator (r-tPA) is an approved treatment for select patients with acute ischemic stroke (AIS). Data indicate r-tPA improves functional outcome three months after AIS compared with placebo. This study models the increase in quality adjusted life years (QALYs) associated with r-tPA compared with similar patients not treated with r-tPA. METHODS: Hospital discharge data for AIS and r-tPA were obtained from the Nationwide Inpatient Sample from 1998 to 2011. Discharge location (home, rehabilitation, long-term care, death) was mapped to modified Rankin Scale (mRS) scores based on National Institute of Neurological Disorders and Stroke (NINDS) Study Group Part 1 and 2 clinical studies. The mRS scores were mapped to relative risk of death and QALYs obtained from the literature. The model estimated expected survival and QALYs by age, gender and mRS for patients receiving r-tPA. Life expectancy and QALYs for patients not receiving r-tPA were estimated based on discharge location and mRS for placebo patients in the NINDS study. RESULTS: AIS discharges declined from over 635,000 in 1998 to over 593,000 in 2011. A total of 183,235 patients received r-tPA. Utilization of r-tPA increased from 1% of AIS patients in 1998 to over 4% in 2011. Estimated projections for QALYs gained from utilization of r-tPA to QALYS without r-tPA were just under 240,000 for the 13 years and with no discounting, and just over 165,000 assuming 3% annual discounting. In the most conservative scenario, assuming no difference in proportional discharge status (i.e. patients not treated with r-tPA are discharged in the same manner as r-tPA patients), the estimated life years gained are approximately 35,000 and QALYS gained are approximately 90,000. CONCLUSIONS: r-tPA for AIS has resulted in estimated gains in quality-adjusted life years due to reduction in disability and improvement in functioning since its introduction in 1998.

Estimated Life-Years Saved in Women with HER2-Positive Metastatic Breast Cancer Receiving First-Line Trastuzumab and Pertuzumab in the United States.

BACKGROUND: HER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab. OBJECTIVES: The first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC. In addition, based on these estimates, the second aim was to project the life-years that could be saved by adding pertuzumab to trastuzumab in first-line therapy. METHODS: We constructed a simulation model accounting for incidence, testing rates, therapy utilization, and overall survival. The model was run for 1999 to 2013 (15 years) to estimate the life-years saved from using trastuzumab plus chemotherapy instead of chemotherapy alone. The model was also run from 2013 to 2027 (15 years) to project the life-years that might be saved by adding pertuzumab. Uncertainty was incorporated using Monte-Carlo methods. RESULTS: The estimated number of women with HER2+ MBC varied over time, with the peak of 9700 in 2005 and the low of 7700 in 2018. The cumulative incremental life-years saved because of first-line trastuzumab use from 1999 to 2013 was estimated to be 156,413 (95% simulation interval 114,840-195,201). The projection for pertuzumab from 2013 to 2027 was 137,959 (95% simulation interval 56,011-225,069). Exploratory analyses of value showed that pertuzumab, trastuzumab, and chemotherapy is associated with a $1.10 billion gain compared with chemotherapy alone, and adding pertuzumab is associated with a $0.06 billion gain compared with trastuzumab with chemotherapy. CONCLUSIONS: This simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab.

The Lifetime Economic Burden of Inaccurate HER2 Testing: Estimating the Costs of False-Positive and False-Negative HER2 Test Results in US Patients with Early-Stage Breast Cancer.

BACKGROUND: Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results. OBJECTIVES: To develop a US-level model to estimate the effect of tumor misclassification on health care costs and patient quality-adjusted life-years (QALYs). METHODS: Decision analysis was used to estimate the number of patients with early-stage breast cancer (EBC) whose HER2 status was misclassified in 2012. FP results were assumed to generate unnecessary trastuzumab costs and unnecessary cases of trastuzumab-related cardiotoxicity. FN results were assumed to save money on trastuzumab, but with a loss of QALYs and greater risk of disease recurrence and its associated costs. QALYs were valued at $100,000 under a net monetary benefit approach. RESULTS: Among 226,870 women diagnosed with EBC in 2012, 3.12% (n = 7,070) and 2.18% (n = 4,955) were estimated to have had FP and FN test results, respectively. Approximately 8400 QALYs (discounted, lifetime) were lost among women not receiving trastuzumab because of FN results. The estimated incremental per-patient lifetime burden of FP or FN results was $58,900 and $116,000, respectively. The implied incremental losses to society were $417 million and $575 million, respectively. CONCLUSIONS: HER2 tests result in misclassification and nonoptimal treatment of approximately 12,025 US patients with EBC annually. The total economic societal loss of nearly $1 billion suggests that improvements in HER2 testing accuracy are needed and that further clinical and economic studies are warranted.

Cost-effectiveness of recombinant tissue-type plasminogen activator within 3 hours of acute ischemic stroke: current evidence.

BACKGROUND AND PURPOSE: Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. METHODS: A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. RESULTS: r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16-0.66) on average per patient and a lifetime cost-saving of $25,000 (95% confidence range, -$42,500 to -$11,000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. CONCLUSIONS: Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.

Investigation of adverse-event-related costs for patients with metastatic breast cancer in a real-world setting.

BACKGROUND: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2). MATERIALS AND METHODS: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated. RESULTS: On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs. CONCLUSION: Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported.

Identification and cost of adverse events in metastatic breast cancer in taxane and capecitabine based regimens.

PURPOSE: We sought to compare the economic impact of treatment-related adverse events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or capecitabine-based treatment regimens as either first- or second-line (FL or SL) therapy in the US. METHODS: We used healthcare claims data from the Truven Health Analytics MarketScan® Commercial Databases to conduct a retrospective cohort study comparing the economic impact of AEs amongst taxane- and capecitabine-treated mBC patients in the US. We selected women diagnosed with mBC between 2008-2010 who received a taxane or capecitabine as first- or second-line (FL or SL) chemotherapy. Costs related to hospitalization, outpatient services, emergency department visits, chemotherapy and other medications were tabulated and combined to determine total healthcare costs. The incremental monthly costs associated with the presence of AEs compared to no AEs were estimated using generalized linear models, controlling for age and Charlson Comorbidity Index. RESULTS: We identified 15,443 mBC patients meeting inclusion criteria. Adjusted total monthly costs were significantly higher in those who experienced AEs than in those without AEs in both lines of treatment (FL incremental cost: taxanes $1,142, capecitabine $1,817; SL incremental cost: taxanes $1,448, capecitabine $4,437). Total costs increased with the number of AEs and were primarily driven by increased hospitalization amongst those with AEs. CONCLUSIONS: Adverse events in taxane- or capecitabine-treated mBC patients are associated with significant increases in costs. Selecting treatment options associated with fewer AEs may reduce costs and improve outcomes in these patients.

Comparison of treatment patterns and economic outcomes in metastatic breast cancer patients initiated on trastuzumab versus lapatinib: a retrospective analysis.

Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2 directed therapy. This study evaluated these outcomes in patients receiving trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab or lapatinib, on or after March 13, 2007, were selected from the US-based PharMetrics® Integrated Database (2000-2011). Patients were required to be continuously enrolled in their healthcare plan for ≥6 months prior to and ≥30 days following trastuzumab or lapatinib initiation. Trastuzumab or lapatinib discontinuation rates (defined as a gap ≥45 consecutive days) were compared using multivariate Cox proportional-hazards models. HRU and monthly healthcare cost differences were estimated using multivariate negative binomial regression models and generalized linear models, respectively. Among the 643 patients who met the inclusion criteria, 381 and 262 patients were included in the trastuzumab and lapatinib groups, respectively. The majority of the 262 patients receiving lapatinib previously received trastuzumab (N = 171 [65.3%]). After adjustment for potential confounders, when compared to trastuzumab patients, lapatinib patients had a higher rate of treatment discontinuation (hazard ratio [HR] = 1.57; P < 0.001), a higher rate of outpatient visits (not treatment administration related) (IRR = 1.19; P < 0.004), and a lower rate of medical visits associated with treatment administration (IRR = 0.34; P < 0.001). There were no significant differences between the two groups in total monthly healthcare costs ($11,920 vs. $11,898 for trastuzumab and lapatinib patients, respectively; P = 0.451). Findings from our study show that, irrespective of the treatment initiated at index date, disease management in patients with mBC is associated with similar and substantial healthcare costs. Any differences in specific components of healthcare costs were associated with differences in the mode of treatment administration. Approximately 50% of all costs were non-drug related, and future studies should focus on how these costs may be controlled, regardless of mode of treatment administration.

Health care utilization and costs by site of service for nonmetastatic breast cancer patients treated with trastuzumab.

BACKGROUND: Adjuvant trastuzumab treatment is administered to early stage breast cancer patients in physician office (POV) or hospital outpatient (HOP) settings. OBJECTIVE: To identify treatment patterns, utilization, and costs by site of care (POV vs. HOP) of patients with adjuvant treatment of breast cancer with trastuzumab. METHODS: This retrospective analysis identified adult, female breast cancer patients who initiated trastuzumab treatment (index date) from a large U.S. claims database. Inclusion criteria also required ≥ 2 claims for both trastuzumab (from July 1, 2006, to July 31, 2012) and breast cancer (during 6-month pre-index baseline period), no evidence of metastatic breast cancer or other cancers in the baseline period, and continuous enrollment with commercial or Medicare Advantage coverage 6 months pre- and post-index, except that patients who died during follow-up were retained. Patients with evidence of trastuzumab receipt during the baseline period or more than 1 site of care during follow-up were excluded. Patients were stratified by site of care and were followed from index date to 30 days after the last trastuzumab infusion prior to a gap ≥ 90 days, death, disenrollment, or end-of-study period. Differences in treatment patterns between the POV and HOP cohorts were assessed by t-test and chi-square test. The relationship between site of care and health care costs was modeled with a generalized linear model with gamma distribution and log link, and the number of trastuzumab infusions was modeled with negative binomial regression controlling for log follow-up time. All models were adjusted for age, baseline comorbidity score, and insurance type. RESULTS: Of the 3,439 breast cancer patients identified, 77.6% (2,669) received adjuvant trastuzumab in the POV setting. Mean age (53.7 years) and baseline comorbidity score (3.91) were similar among cohorts; a higher percentage of POV versus HOP patients had commercial insurance (91.1% vs. 86.4%, P < 0.001). Compared with the POV cohort, HOP patients had a shorter mean duration of trastuzumab treatment (324.8 vs. 343.0 days, P < 0.001); more treatment gaps (30-59 day gap: 67.4% vs. 24.1%, P < 0.001); and fewer trastuzumab infusions per month (1.37 vs. 1.98, P < 0.001) during follow-up. In multivariate analysis, the monthly count of trastuzumab infusions in the HOP cohort was lower than the POV cohort (incidence rate ratio = 0.693; 95% CI = 0.672-0.715). Adjusted per patient per month total health care costs were 53.6 % higher in the HOP setting (cost ratio = 1.536, 95% CI = 1.472-1.604). CONCLUSIONS: Breast cancer patients treated with adjuvant trastuzumab in the HOP setting had a shorter duration of trastuzumab treatment and fewer trastuzumab infusions but incurred higher monthly total costs than patients treated in the POV setting.

Assessing the potential cost-effectiveness of retesting IHC0, IHC1+, or FISH-negative early stage breast cancer patients for HER2 status.

BACKGROUND: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) tests are commonly used to assess human epidermal growth factor 2 (HER2) status of tumors in patients with breast cancer. This analysis evaluates the likely cost-effectiveness of expanded retesting to assess HER2 tumor status in women with early stage breast cancer. METHODS: We developed a decision-analytic model to estimate the incremental cost-effectiveness ratio (ICER) of expanded reflex testing from a US payer perspective. Expanded reflex testing is defined as retesting tumor specimens from patients whose tumors are IHC0, IHC1+, or FISH-negative on their first test. In the base case, we assumed that 80% of patient tumors are initially IHC-tested and 20% are FISH-tested. Testing outcomes for IHC and FISH with and without retesting were based on published meta-analyses. The cost of tests and treatment and the long-term health outcomes were obtained from the literature. RESULTS: In the base case, we estimated that 2.27% of women who received expanded reflex testing would be HER2-positive and receive trastuzumab treatment: the projected ICER was $36,721 per life year or $39,745 per quality-adjusted life year (QALY). This varied between $47,100 per QALY and $35,500 per QALY if we assumed that 1%-8% of patients retested were then HER2+, respectively. The results of deterministic and probabilistic sensitivity analysis were robust. This strategy would result in 4700 (2000-17,000) patients being eligible to receive trastuzumab treatment annually. CONCLUSIONS: Retesting patients who are IHC0, IHC1+, or FISH-negative is projected to be a cost-effective clinical strategy.

Estimating recurrences prevented from using trastuzumab in HER-2/neu-positive adjuvant breast cancer in the United States.

BACKGROUND: Breast cancer recurrence is associated with significant morbidity, mortality, and cost. Patients with early stage HER2+ tumors are at increased risk of recurrence. The use of trastuzumab for these patients has been shown to reduce recurrences and improve overall survival. METHODS: A Monte Carlo simulation was conducted based on Surveillance, Epidemiology, and End Results incidence rates for 2005, United States Census data for 2005, and the results of key trials of the adjuvant use of trastuzumab. Patients included in this analysis had incident, HER2+, stage I to III breast cancer. The number of recurrences that could be prevented with trastuzumab, the cardiac adverse events that might occur, and the associated cost savings were estimated. RESULTS: Approximately 31,200 women had HER2+ breast cancer in 2005, of whom 7298 would have had a recurrence over the subsequent 5 years despite standard of care adjuvant treatment. If trastuzumab were added to their regimen, 2791 women might have avoided recurrence, and 948 may have had an asymptomatic or symptomatic cardiac adverse event, for a ratio of expected recurrences to cardiac adverse events of 3.2 (95% confidence interval, 1.5-5.9). In economic terms, avoidance of future breast cancer recurrences was associated with lifetime reduction in future direct and indirect costs on the order of $240 million to $1.7 billion. CONCLUSIONS: On the basis of the simulation results, targeting HER2+ tumors with trastuzumab in the adjuvant setting should prevent a significant number of women from recurrence events, with important outcomes for patients, physicians, payers, and society.

Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer.

BACKGROUND: Adding trastuzumab to adjuvant chemotherapy provides significant clinical benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A cost-effectiveness analysis was performed to assess clinical and economic implications of adding trastuzumab to adjuvant chemotherapy, based upon joint analysis of NSABP B-31 and NCCTG N9831 trials. METHODS: A Markov model with 4 health states was used to estimate the cost utility for a 50-year-old woman on the basis of trial results through 4 years and estimates of long-term recurrence and death based on a meta-analysis of trials. From 6 years onward, rates of recurrence and death were assumed to be the same in both trastuzumab and chemotherapy-only arms. Incremental costs were estimated for diagnostic and treatment-related costs. Analyses were from payer and societal perspectives, and these analyses were projected to lifetime and 20-year horizons. RESULTS: Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year (QALY; discount rate 3%) gained was 26,417 dollars (range 9,104 dollars-69,340 dollars under multiway sensitivity analysis). Discounted incremental lifetime cost was 44,923 dollars, and projected life expectancy was 3 years longer for patients who received trastuzumab (19.4 years vs 16.4 years). During a 20-year horizon, the projected cost of adding trastuzumab to chemotherapy was 34,201 dollars per QALY gained. Key cost-effectiveness drivers were discount rate, trastuzumab price, and probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis. CONCLUSIONS: Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments.

Clinical and economic burden of psoriasis.

In an effort to assess the burden associated with psoriasis, the MEDLINE database and bibliographies of articles published from 1975 through 2004 were searched, emphasizing patients with moderate-to-severe disease, to summarize the current understanding on various aspects of disease burden. The clinical burden of psoriasis is both well documented and significant. The disease is debilitating: Sufficient disease severity interferes with patients' work and day-to-day living. Perhaps even more damaging is the psychosocial toll psoriasis exacts on the afflicted. Numerous studies document the extent of mental and emotional anguish, features not often revealed through objective measures. Successful treatment must focus on improving a patient's quality of life as well as reducing the clinical features of psoriasis. The economic burden is also significant, though far fewer studies of the associated indirect costs have been published in the literature.