Impact of JIA on parents' work absences.

OBJECTIVE: Children with JIA have long-term morbidity and require extensive parental assistance. This study aimed to evaluate the impact of having a child with JIA on parents' missed work time, which can lead to decreased work productivity. METHODS: The Truven Health MarketScan Commercial Database (2000-9) was accessed to identify a cohort of parents having a child with newly diagnosed JIA. For comparison, a cohort of parents having no children with JIA was identified and matched with the preceding cohort. Parents' work absences were analysed using descriptive statistics and multivariable regression. Estimates were weighted to be generalizable to the US employer-sponsored insurance population. RESULTS: The study identified 108 parents having a child with newly diagnosed JIA (mean age 42.5 years), representing an estimated 3335 (weighted) parents nationally. Most of them were from the South (45%), male (71%) and employed in the transportation and utilities industry (58%). The demographic characteristics of the control cohort of parents were generally similar. Children with JIA (mean age 10.6 years) represented an estimated 3528 cases nationally. The mean number of reported missed work-time hours was 281.81 (s.e. 40.50) in a 9 year period for parents having a child with JIA compared with other parents 183.36 (28.55). Work-time loss was significantly related to having a child with JIA, sex and geographical region of residence. Parents having a child with JIA were 2.78 times more likely to report work-time loss [odds ratio (OR) 2.78 (95% CI 1.47, 5.26)] than those having no children with JIA. CONCLUSION: Parents having a child with JIA report significant work-time loss compared with parents with no children having JIA, particularly during the year following the child's diagnosis.

Reliability and Validity of the Work Instability Scale for Rheumatoid Arthritis.

OBJECTIVE: The objective was to evaluate the psychometric properties of the Rheumatoid Arthritis-Work Instability Scale (RA-WIS) in a clinical trial setting. METHODS: Secondary analyses were conducted using data from a 56-week, randomized controlled trial of patients with early rheumatoid arthritis (RA). Patient-reported outcome measures included the RA-WIS, the Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Quality of Life Questionnaire, and the Global Assessment of Disease Activity and Pain, data for which were collected at baseline and at weeks 12, 16, 24, and 56. Data were analyzed for reliability, validity, and responsiveness. RESULTS: Among 148 patients whose data were analyzed, more than half were women (56.1%) with a mean age of 46.8 years. On average, patients experienced RA symptoms for 8.7 months; the mean 28-Joint Disease Activity Score (DAS28) was 5.9, and the mean HAQ - Disability Index was 1.3. The RA-WIS demonstrated excellent internal consistency and test-retest reliability (α = 0.89 and intraclass correlation coefficient = 0.91, respectively). At baseline and week 24, moderate to strong correlations were seen between RA-WIS total scores and the HAQ, the Global Assessment of Disease Activity, and the Pain Rheumatoid Arthritis Quality of Life Questionnaire, ranging from 0.47 to 0.81 (all P < 0.0001). Mean RA-WIS total scores and work disability risk levels discriminated between clinical severity scores on the DAS28, the HAQ - Disability Index, and the Physician Global Assessment of Disease Activity (all P < 0.05). Mean baseline to week 24 RA-WIS total change scores were significantly different among American College of Rheumatology responder groups (P ≤ 0.0001) and between DAS28 remission status groups (P < 0.001). CONCLUSIONS: These findings provide evidence supporting the reliability, validity, and responsiveness of the RA-WIS for evaluating work disability in patients with RA in a clinical trial setting.

Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate.

OBJECTIVES: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. METHODS: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. RESULTS: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores. CONCLUSIONS: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.

Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study.

OBJECTIVE: To estimate the excess risk of cardiovascular and cerebrovascular diseases among individuals with ankylosing spondylitis (AS) in Quebec compared with the general population of Quebec. METHODS: A retrospective cohort study was conducted using population-based administrative data from Quebec. The cohort included all adult individuals with at least 1 AS diagnosis on physician billing or hospital discharge records between 1996 and 2006. A comparison cohort was generated using a 1% random sample of individuals without AS. Cardiovascular and cerebrovascular diseases, and associated hospitalizations, were classified into 1 of 6 subcategories: congestive heart failure, valvular (aortic or nonaortic) heart disease, ischemic heart disease, cerebrovascular disease, or "other" cardiovascular disease. The age- and sex-stratified prevalence estimates, and standardized prevalence ratios, of cardiovascular or cerebrovascular disease in patients with AS, compared to that in the general population, were calculated. RESULTS: The AS cohort included 8,616 individuals diagnosed over the period 1996-2006. The prevalence of cardiovascular and cerebrovascular diseases increased with increasing age for all cardiovascular disease subgroups, and was similar for individuals of both sexes. Age- and sex-stratified prevalence ratios were highest in younger individuals with AS. The age- and sex-standardized prevalence ratios comparing the risk among those with AS to the risk in the general population were as follows: for aortic valvular heart disease 1.58 (95% confidence interval [95% CI] 1.31-1.91), for nonaortic valvular heart disease 1.58 (95% CI 1.43-1.74), for ischemic heart disease 1.37 (95% CI 1.31-1.44), for congestive heart failure 1.34 (95% CI 1.26-1.42), for "other" cardiovascular disease 1.36 (95% CI 1.29-1.44), for cerebrovascular disease 1.25 (95% CI 1.15-1.35), and for any hospitalization for a cardiovascular or cerebrovascular disease 1.31 (95% CI 1.22-1.41). CONCLUSION: Compared with the general population, patients with AS are at increased risk for many types of cardiovascular and cerebrovascular diseases, and are more likely to be hospitalized for these diseases. The excess risk is greatest in younger patients with AS.

Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

PURPOSE: Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. METHODS: A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. FINDINGS: Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. IMPLICATIONS: Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications.

Disparities in care by insurance status for individuals with rheumatoid arthritis: analysis of the medical expenditure panel survey, 2006-2009.

OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) recommend early, aggressive treatment with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs) to minimize long-term disability. We aimed to assess differences in medical resource utilization, drug therapy, and health outcomes among RA patients by insurance type in the United States. METHODS: Individuals with a self-reported diagnosis of RA were identified in the Medical Expenditure Panel Survey (MEPS) database, 2006-2009. Data regarding sociodemographic characteristics, insurance type and status, and outcomes (including health care resource utilization, prescription medication use, health status, and patient-reported barriers to health care) were extracted. Multivariable regression analyses were used to examine the impact of insurance type (private, Medicare, Medicaid, or uninsured) on outcome measures while controlling for age group, sex, and race/ethnicity. RESULTS: A total of 693 individuals with a self-reported diagnosis of RA during the study period were identified; 423 were aged 18-64 years and 270 were aged ≥65 years. Among patients aged 18-64, those with Medicaid or who were uninsured were less likely than those with private insurance to visit a rheumatologist (adjusted odds ratio [aOR] 0.13 and 0.17, respectively; p < .001) and to receive biologic DMARDS (aOR 0.09 [p < .001] and 0.16 [p < .01], respectively); those with Medicaid were also less likely to receive nonbiologic DMARDS (aOR 0.26 [p < .01]). Those with Medicaid were more likely than those with private insurance to be unable/delayed in getting prescription drugs (aOR 2.9 [p < .05]), to experience cognitive, social, and physical limitations (aOR 8.7 [p < .001], 4.7 [p < .001], and 2.5 [p < .05], respectively); they also reported significantly lower general health and health-related quality of life. Patients aged ≥65 experienced greater equity in care and outcomes. CONCLUSIONS: Younger RA patients with Medicaid (including those who receive coverage under the Medicaid expansion component of the Affordable Care Act) may be at risk for inadequate treatment.

A comparison of 5 days of therapy with cefdinir or azithromycin in children with acute otitis media: a multicenter, prospective, single-blind study.

BACKGROUND: Short-course therapy for acute otitis media (AOM) improves adherence and may reduce secondary bacterial resistance. METHODS: In this multicenter, prospective, investigator-blinded study, patients between the ages of 6 months and 6 years with a clinical diagnosis of AOM were randomized to receive cefdinir oral suspension 7 mg/kg q12h for 5 days or azithromycin oral suspension 10 mg/kg once daily on day 1 and 5 mg/kg once daily on days 2 through 5. Clinical response was assessed at the end-of-therapy (EOT) visit (days 7-9) and the follow-up visit (days 20-25). RESULTS: Three hundred fifty-seven patients were enrolled in the study. The treatment groups were similar at baseline with respect to demographic characteristics (mean [SD] age, 3.0 [1.7] years; 55% male), incidence of bilateral AOM (45%), and presenting signs and symptoms. The majority of evaluable children (77%) had previously received conjugated heptavalent pneumococcal vaccine (PCV7) against Streptococcus pneumoniae. At the EOT visit, clinical cure rates were comparable for cefdinir and azithromycin (87% [151/174] and 85% [149/176], respectively; 95% CI, -5.5 to 9.8). In addition, clinical cure rates at the EOT visit in the children who had been vaccinated with PCV7 were comparable between cefdinir and azithromycin (86% vs 83%; 95% CI, -6.5 to 11.8). No significant difference in clinical cure rates was observed at the follow-up visit (76% and 86%; 95% CI, -18.9 to 0.0). Parental satisfaction was similar between treatment groups with regard to ease of use, taste, compliance, health care resource utilization, and missed days of work and day-care. Both antibiotics were well tolerated; diarrhea and abnormal stools were the most common antibiotic-related adverse events (< or = 7% each). CONCLUSIONS: Short courses (5 days) of therapy with cefdinir or azithromycin were comparable in these children with AOM based on clinical end points, parental preferences, and health care utilization.

Impact of Switching From an Initial Tumor Necrosis Factor Inhibitor on Health Care Resource Utilization and Costs Among Patients With Rheumatoid Arthritis.

PURPOSE: Despite improved clinical outcomes for the majority of patients, nearly 30% of patients with rheumatoid arthritis (RA) who initiate tumor necrosis factor antagonist (anti-TNF) biologic agents fail to respond to their first-line anti-TNF and switch to another anti-TNF or a non-TNF biologic. How this change affects health care costs and resource utilization is unknown. We therefore compared RA patients taking first-line anti-TNFs who switched to a second anti-TNF versus those patients who switched to an alternate biologic. METHODS: Health care claims data were obtained from a large US database for eligible adults with confirmed RA diagnoses who initiated anti-TNF treatment and switched to another biologic. Health care costs and utilization during the first 12 months' postswitch were compared. Generalized linear models were used to adjust for differences in demographic and clinical characteristics before switching. FINDINGS: Patients who switched to a second anti-TNF rather than a non-TNF biologic were generally younger (53.0 vs. 55.3 years; P < 0.0001) and less likely to be female (79.7% vs. 82.7%; P = 0.0490). Of the 3497 eligible patients who switched from first-line anti-TNFs, 2563 (73.3%) switched to another anti-TNF and 934 (26.7%) switched to a non-TNF. Adalimumab was the most frequently prescribed (43.4%) second-line anti-TNF, and abatacept was the most common non-anti-TNF (71.4%). Patients who switched to a second anti-TNF remained on their first medication for a significantly shorter period (342.5 vs 420.6 days; P < 0.0001) and had lower comorbidity indices and higher disease severity at baseline than those who switched to a non-anti-TNF. After adjusting for baseline differences, patients who switched to second anti-TNFs versus a non-TNF incurred lower RA-related costs ($20,938.9 vs $22,645.2; P = 0.0010) and total health care costs ($34,894.6 vs $38,437.2; P = 0.0010) 1 year postswitch. These differences were driven by increased physician office visit costs among the non-TNF group. IMPLICATIONS: Among the anti-TNF initiators who switched therapy, more patients switched to a second anti-TNF than to a non-TNF. Switching to a second anti-TNF treatment was associated with lower all-cause and RA-related health care costs and resource utilization than switching to a non-TNF. Because switching therapy may be unavoidable, finding a treatment algorithm mitigating this increase to any extent should be considered. These data are limited by their retrospective design. Additional confounding variables that could not be controlled for may affect results.

Modelling the cost-effectiveness of combination therapy for early, rapidly progressing rheumatoid arthritis by simulating the reversible and irreversible effects of the disease.

OBJECTIVE: To estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function. METHODS: A microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs). RESULTS: When both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106,207 for a resulting incremental cost/QALY gain of £32,425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27,238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78,809 (when only direct costs were included). CONCLUSIONS: Starting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered.

Parent-reported outcomes for treatment of acute otitis media with cefdinir or amoxicillin/clavulanate oral suspensions.

OBJECTIVE: To compare parent-reported outcomes (satisfaction, tolerability, compliance, and work/daycare missed) for children (aged 6 months to 6 years) receiving either cefdinir or amoxicillin/clavulanate for acute otitis media. METHOD: In a phase IV, investigator-blinded, parallel-group, randomized, multicenter study, parents or legal guardians were asked to complete the Otitis Parent Questionnaire (OPQ) 12-14 days after the first dose of cefdinir or amoxicillin/clavulanate oral suspensions. Responses in each of the outcome domains were analyzed using non-parametric statistical analysis. RESULTS: Of 367 parents/guardians who completed the questionnaire, better ease of use (p = 0.009) and taste (p < 0.0001) were associated with cefdinir versus amoxicillin/clavulanate treatment, and children were significantly more likely to experience vomiting with amoxicillin/clavulanate (16% vs 8%; p = 0.016). Parents also reported that their children were much more likely to take all of their medication if receiving cefdinir (68% vs 53% for amoxicillin/clavulanate; p = 0.005). There were no statistically significant differences between groups in work/daycare missed. CONCLUSION: Based on parents' assessment using the OPQ, cefdinir was easier to administer and tasted better than amoxicillin/clavulanate. Children who received cefdinir also experienced less vomiting and had greater compliance than children who received amoxicillin/clavulanate.

Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany.

OBJECTIVE: To obtain detailed real-world data on persistence and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in rheumatoid arthritis (RA) patients treated in Germany. METHODS: In this retrospective observational study claims data of a major German health insurance fund between 2005 and 2008 were analysed. Patients receiving at least one prescription of adalimumab, etanercept or infliximab were identified and categorised as "TNF inhibitor naive" or "TNF inhibitor continuing". For the calculation of TNF inhibitor persistence a survival analysis with the Kaplan-Meier estimator was used. A Cox regression was used to analyse, if any relevant factors were influencing persistence. Dosage increase rates were analysed for adalimumab, etanercept and infliximab. Sensitivity analyses based on variations in gap length were conducted. RESULTS: A total of 2,201 RA patients were identified. 1,468 of these patients were TNF inhibitor naive patients and 733 were defined as TNF inhibitor continuing patients. There were no significant differences in the treatment persistence rates between adalimumab, etanercept and infliximab for TNF inhibitor naive and continuing patients. The persistence rate after three years was 22.47% for adalimumab, 24.27% for etanercept and 21.49% for infliximab naive patients. For continuing patients, the persistence rate after three years was 32.88% for adalimumab, 30.95% for etanercept, and 33.90% for infliximab, respectively. Gender, medication and Charlson Comorbidities Index did not influence the persistence significantly. Dosage increase occurred in 7.3% adalimumab, 1.4% etanercept, and 17.2% infliximab naive patients and 5.8%, 1.1% and 11.9% respectively in the continuing patients. CONCLUSIONS: In this study, there were no significant differences in persistence among adalimumab, etanercept and infliximab treated patients. Consistent with previous research, there was a higher dose escalation for infliximab than for the two subcutaneous treatments, adalimumab or etanercept.

Estimating the occurrence of renal complications among persons with ankylosing spondylitis.

OBJECTIVE: The few published estimates of the risk of renal complications in ankylosing spondylitis (AS) are established on clinic-based studies. Our objective was to estimate the age- and sex-specific risks of renal complications in a population-based cohort of AS subjects in Québec between 1996 and 2006, relative to the general population. METHODS: A retrospective cohort design was implemented using population-based administrative data collected from 1996 to 2006 in Québec, Canada. The study cohort included subjects diagnosed with AS on physician billing records, and the comparison cohort comprised a 1% random sample of subjects without AS. Age- and sex-stratified prevalence ratios for acute kidney injury, chronic kidney disease, amyloidosis, and hypertensive renal disease were compared between subjects with and without AS. RESULTS: The AS cohort included 4,836 men and 3,780 women. Renal complications were diagnosed among 3.4% of men and 2.1% of women with AS compared with 2.0% and 1.6% of persons without AS, respectively. Renal complications were 72% more prevalent among persons with AS and an increase was observed in each of the conditions. The magnitude of the risk of renal complications was highest among younger individuals and decreased with advancing age. CONCLUSION: These findings indicate that renal complications may be elevated among persons with AS, especially at younger ages. Despite the limitations of administrative data pertaining to onset of disease, these findings warrant further investigation because of their clinical relevance.

Worker productivity outcome measures: OMERACT filter evidence and agenda for future research.

The objective of the Outcome Measures in Rheumatology (OMERACT) Worker Productivity working group is to identify worker productivity outcome measures that meet the requirements of the OMERACT filter. At the OMERACT 11 Workshop, we focused on the at-work limitations/productivity component of worker productivity (i.e., presenteeism) - an area with diverse conceptualization and instrumentation approaches. Various approaches to quantify at-work limitations/productivity (e.g., single-item global and multi-item measures) were examined, and available evidence pertaining to OMERACT truth, discrimination, and feasibility were presented to conference participants. Four candidate global measures of presenteeism were put forth for a plenary vote to determine whether current evidence meets the OMERACT filter requirements. Presenteeism globals from the Work Productivity and Activity Impairment Questionnaire (72% support) and Rheumatoid Arthritis-specific Work Productivity Survey (71% support) were endorsed by conference participants; however, neither the presenteeism global item from the Health and Work Performance Questionnaire nor the Quantity and Quality method achieved the level of support required for endorsement at the present time. The plenary was also asked whether the central item from the Work Ability Index should also be considered as a candidate measure for potential endorsement in the future. Of participants at the plenary, 70% supported this presenteeism global measure. Progress was also made in other areas through discussions at individual breakout sessions. Topics examined include the merits of various multi-item measures of at-work limitations/productivity, methodological issues related to interpretability of outcome scores, and approaches to appraise and classify contextual factors of worker productivity. Feedback gathered from conference participants will inform the future research agenda of the working group.

Annual incremental health benefit costs and absenteeism among employees with and without rheumatoid arthritis.

OBJECTIVE: To assess the impact of rheumatoid arthritis (RA) on absence time, absence payments, and other health benefit costs from the perspective of US employers. METHODS: Retrospective regression-controlled analysis of a database containing US employees' administrative health care and payroll data for those who were enrolled for at least 1 year in an employer-sponsored health insurance plan. RESULTS: Employees with RA (N = 2705) had $4687 greater average annual medical and prescription drug costs (P < 0.0001) and $525 greater (P < 0.05) indirect costs (because of sick leave, short- and long-term disability, and workers' compensation absences) than controls (N = 338,035). Compared with controls, the employees with RA used an additional 3.58 annual absence days, including 1.2 more sick leave and 1.91 more short-term disability days (both P < 0.0001). CONCLUSION: Employees with RA have greater costs across all benefits than employees without RA.

Matching-adjusted indirect comparison of adalimumab vs etanercept and infliximab for the treatment of psoriatic arthritis.

OBJECTIVES: No head-to-head trial has compared the efficacy of adalimumab vs etanercept and infliximab for psoriatic arthritis (PsA). This study implements a matching-adjusted indirect comparison technique to address that gap. METHODS: Patient-level data from a placebo-controlled trial of adalimumab (ADEPT) were re-weighted to match average baseline characteristics from pivotal published trials of etanercept and infliximab. ADEPT patients were re-weighted by odds of enrollment in comparator trials, estimated using logistic regression. Matched-on characteristics included PsA duration, age, gender, severity, active psoriasis, and concomitant treatment. After matching, placebo-adjusted treatment arms were compared at weeks 12 (or 14) and 24. Outcomes included ACR20/50/70, PsARC, HAQ, and modified TSS. PASI50/75/90 were compared for patients with active psoriasis. Cost per responder (CPR) was assessed in the US and Germany using matching-adjusted end-points and drug list prices. Statistical significance was assessed using weighted t-tests. RESULTS: After matching, adalimumab-treated patients had greater placebo-adjusted rates of ACR70 and PASI50/75/90 at week 24 compared with etanercept (all p < 0.05). Adalimumab patients had a higher placebo-adjusted rate of ACR70 than infliximab at week 14 (p = 0.034). Adalimumab treatment had lower CPR for ACR70 and PASI50/75/90 compared with etanercept at week 24, in both the US and Germany (all p < 0.02). Adalimumab had lower CPR than infliximab for all outcomes at week 24 (all p < 0.05). CONCLUSION: Adalimumab is associated with higher ACR70 and PASI50/75/90 response rates than etanercept at week 24 and a higher ACR70 response rate than infliximab at week 14. Adalimumab has significant advantages over etanercept and infliximab in CPR across multiple end-points. KEY LIMITATIONS: The matching-adjusted indirect comparison method cannot account for unobserved differences in patient characteristics across trials, and only a head-to-head randomized clinical trial can fully avoid the limitations of indirect comparisons. CPR findings are limited to the US and German markets, and may not be generalizable to other markets with different relative pricing.

Prevalence of axial spondyloarthritis in United States rheumatology practices: Assessment of SpondyloArthritis International Society criteria versus rheumatology expert clinical diagnosis.

OBJECTIVE: New classification criteria for axial spondyloarthritis (SpA) have been validated by the Assessment of SpondyloArthritis international Society (ASAS) working group. We applied these criteria to estimate prevalence of SpA in randomly selected, retrospectively reviewed medical records from representative US rheumatology practices. METHODS: Rheumatologists from 101 US practices identified at-risk patients, ages 18-44 years, with chronic back pain. Medical records were reviewed against ASAS criteria. The proportion of patients meeting ASAS criteria was compared to an estimate of the total number of at-risk patients treated at participating sites and, following weighting, was extrapolated to 5,520 US rheumatology practices. US Census data were used to estimate national prevalence. RESULTS: In a sample of 816 randomly selected records, 514 (63%) at-risk patients (95% confidence interval [95% CI] 59.6-66.3%) met ASAS criteria. By applying this proportion to 1,217,097 Americans estimated at risk, 766,652 were projected to meet ASAS criteria. This projection corresponds to a national prevalence of 0.70% (95% CI 0.38-1.1%) or 701 per 100,000 individuals. The prevalence estimates of ankylosing spondylitis and nonradiographic axial SpA are 0.35% (95% CI 0.18-0.554%) and 0.35% (95% CI 0.18-0.554%), respectively. Rheumatologists diagnosed axial SpA in 491 (60%) of those at risk, corresponding to 0.67% (95% CI 0.36-1.01%) prevalence overall. However, of 514 patients meeting ASAS criteria, 124 (24%) were undiagnosed by rheumatologists. CONCLUSION: This is the first systematic epidemiology study of axial SpA using ASAS criteria. Better recognition of axial symptoms is needed, as rheumatologists' expert clinical diagnoses are not always in agreement with ASAS criteria.

Health-related quality of life outcomes of adalimumab for patients with early rheumatoid arthritis: results from a randomized multicenter study.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with significant impairments in health-related quality of life (HRQOL). We evaluated patient-reported outcomes including HRQOL outcomes following adalimumab plus methotrexate (MTX) therapy in patients with early RA. METHODS: PREMIER was a phase III, multicenter, randomized, double-blind, active-comparator clinical trial in early RA. Patients aged ≥ 18 years were randomly assigned to receive adalimumab 40 mg every other week (eow) plus weekly MTX, weekly MTX, or adalimumab 40 mg eow for 104 weeks. American College of Rheumatology (ACR) criteria were used to evaluate clinical efficacy and response. Outcomes were assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form 36 Health Survey (SF-36), Short-Form 6 Dimension (SF-6D), visual analog scale (VAS) assessments of global disease activity (patient's global assessment; PtGA) and pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Health Utility Index Mark 3 (HUI-3). RESULTS: Of 799 patients enrolled, 268 received adalimumab plus MTX, 257 received MTX monotherapy, and 274 received adalimumab monotherapy. Patients treated with adalimumab plus MTX demonstrated significant baseline to Week 104 improvements in HAQ-DI (p < 0.0001), SF-36 Physical Component Summary (p < 0.0001), 4 SF-36 domains [physical function (p < 0.0001), bodily pain (p <0.0001), vitality (p = 0.0139), role limitations-physical (p = 0.0005)], SF-6D (p = 0.0152), VAS-PtGA (p < 0.0001), VAS-pain (p < 0.0001), FACIT-F (p < 0.0001), and HUI-3 (p = 0.0034) scores versus patients treated with MTX monotherapy. Both SF-6D and HUI-3 were found to be sensitive preference-based measures for assessing the effects of treatment on multidimensional function. No clinically meaningful differences between adalimumab and MTX monotherapy groups were observed for most measures. For each measure, there was significant association between HRQOL improvement and ACR clinical response. CONCLUSION: Adalimumab plus MTX significantly improved physical functioning and HRQOL in patients with early RA over 2 years of treatment. (ClinicalTrials.gov identifier NCT00195663).

Changes in utilization and costs for patients with rheumatoid arthritis, 1997 to 2006.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that often results in joint pain, inflammation and bone erosions. Perhaps the most notable change in RA treatment during the last decade is the advent of biologics, and, in particular, anti-tumour necrosis factor agents. Given these advances, it is useful to assess how healthcare and work-loss costs of patients with RA have changed. OBJECTIVE: Our objective was to assess changes in healthcare utilization and costs from 1997 to 2006 for patients diagnosed with RA. METHODS: Two cohorts (1997 and 2006) of patients with RA and matched controls were identified from two administrative claims databases along with subsamples of employed patients and matched controls. The analysis focused on the more homogeneous employee subsample. We compared annual excess co-morbidity rates, resource utilization and healthcare and work-loss costs per patient between the 1997 (n = 279) and 2006 cohorts (n = 837) with difference-in-differences methodology. Results with p < 0.05 were considered statistically significant. RESULTS: In the employee subsample, there were no statistically significant differences in the excess prevalence of non-RA co-morbidities or Charlson Co-morbidity Index results, except for cardiovascular disease, which decreased by 11.1%. Excess number of ED visits and days hospitalized decreased by 1.1 visits/patient and 0.9 days/patient, respectively, while rheumatologist visits increased by 0.9 visits/patient. Excess per-patient direct costs were unchanged. However, drug costs increased by $US633/patient, but medical costs decreased by $US618/patient (not significant) [year 2006 values]. CONCLUSION: For employed patients with RA, there were significant reductions in per-patient excess hospital days, as well as ED visits, and no changes in excess total direct costs over time. New treatments introduced during the study period may be associated with cost savings that offset changes in employee utilization of drug and medical services. In addition, the reductions in excess ED visits and hospital days suggest improvements in patient quality of life.

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents.

OBJECTIVE: To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients. METHODS: Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review. RESULTS: The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p=0.26 vs etanercept; p=0.86 vs adalimumab), adalimumab (p=0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p<0.001 vs etanercept; p=0.18 vs adalimumab), 0.63 for adalimumab (p=0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France). CONCLUSIONS: Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.

Cost per responder associated with biologic therapies for Crohn's disease, psoriasis, and rheumatoid arthritis.

INTRODUCTION: Biologic therapies have demonstrated efficacy and safety in several chronic systemic disorders. The authors indirectly compared response rates and costs per responder associated with biologic treatments for moderate-to-severe Crohn's disease (CD), psoriasis (Ps), and/or rheumatoid arthritis (RA). METHODS: A systematic literature search was performed to identify phase 3 randomized controlled trials of biologics for CD (adalimumab, infliximab), Ps (adalimumab, etanercept, infliximab, ustekinumab 45 mg, ustekinumab 90 mg), or methotrexate-refractory RA (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab). Food and Drug Administration-approved dosing schedules were evaluated. Published response rates were extracted, with response defined in CD, Ps, and RA as: ≥70-point reduction in CD Activity Index at 12 months; ≥75% improvement in Psoriasis Area and Severity Index at 3 months; and ≥50% improvement in American College of Rheumatology component scores at 6 months. Within each indication, mixed-treatment comparison meta-analyses were conducted to derive pooled estimates and 95% CIs of response rate difference versus placebo for each biologic, adjusting for cross-trial variation in control-arm response rates. Cost per responder was estimated for each biologic as projected per patient drug costs (2011 US$) divided by response rate difference. RESULTS: Altogether, 23 publications were selected. In CD, 12-month cost per responder was estimated at $116,291 (95% CI $71,637-208,348) for adalimumab and $125,169 (95% CI $60,532-267,101) for infliximab. Among biologics approved in Ps, 3-month cost per responder was lowest for adalimumab ($9,756; 95% CI $8,668-11,131), infliximab ($12,828; 95% CI $11,772-13,922), and ustekinumab 45 mg ($13,821; 95% CI $12,599-15,167). In RA, biologics with the lowest 6-month cost per responder were adalimumab ($27,853; 95% CI $19,284-40,270), etanercept ($29,140; 95% CI $14,170-61,030), and tocilizumab ($31,363; 95% CI $14,713-64,232). CONCLUSION: Meta-analyses of clinical trials found considerable variation in cost-effectiveness of biologic therapies for CD, Ps, and RA. These results may help determine biologic utilization in these chronic diseases.