5-ASA to sulfasalazine drug switch program in patients with ulcerative colitis.

OBJECTIVES: To switch patients with ulcerative colitis (UC) from costlier 5-aminosalicylic acid compounds to sulfasalazine and assess (1) the cost savings, (2) the barriers to switching, and (3) adverse events (AEs) and adherence at 3 months after the drug switch. STUDY DESIGN: An open-label, pharmacist-administered drug switch program coordinated at an academic inflammatory bowel disease center. METHODS: A clinical pharmacist contacted patients with UC who were prescreened by physicians and covered by specific insurers to enroll them in the drug switch program. Enrolled patients were followed for 3 months to assess AEs and medication adherence. Reasons for declining to participate were recorded. RESULTS: A total of 205 eligible patients were identified; only 14 enrolled, and 10 remained on sulfasalazine for the entire 3-month follow-up period. The enrollment rate was only 4.9%, yet a net cost savings of $22,828/3-month to the insurer was achieved (including program administration costs but excluding AE costs), with co-pays reduced by approximately $25 per month per patient. The rate of AEs on sulfasalazine (28.6%) was similar to that found in previous reports. Significant unanticipated barriers to switching were encountered, namely patient desire to not alter an existing effective drug regimen. CONCLUSIONS: A pharmacist-administered drug switch program in patients with UC was significantly more difficult than anticipated, with questionable achievement of cost savings. This experience suggests that future drug switches and studies should focus on patient preferences for drug switching, as this may have implications for switching from brand name to biosimilar drugs.

Cost-effectiveness of clinical remission by treat to target strategy in established rheumatoid arthritis: results of the CREATE registry.

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.

Cost-Effectiveness of Triple Therapy Versus Etanercept Plus Methotrexate in Early Aggressive Rheumatoid Arthritis.

OBJECTIVE: To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started with methotrexate and added either etanercept or sulfasalazine plus hydroxychloroquine to patients with persistent disease activity. METHODS: We built a Markov cohort model that uses individual-level data from the TEAR trial, published literature, and supplemental clinical data. Costs were in US dollars, benefits in quality-adjusted life years (QALYs), perspective was societal, and the time horizon was 5 years. RESULTS: The immediate strategies were more efficacious than step-up strategies. SE and IE were more costly than ST and IT, primarily due to treatment cost differences. In addition, IT was the least expensive and most effective strategy when the time horizon was 1 and 2 years. When the time horizon was 5 years, IE was marginally more effective than IT (3.483 versus 3.476 QALYs), but IE was substantially more expensive than IT ($148,800 versus $52,600), producing an incremental cost-effectiveness ratio of $12.5 million per QALY. These results were robust to both one-way deterministic and joint probabilistic sensitivity analyses. CONCLUSION: IT was highly cost-effective in the majority of scenarios. Although IE was more effective in 5 years, a substantial reduction in the cost of biologic agents was required in order for IE to become cost-effective in early aggressive RA under willingness-to-pay thresholds that most health care settings may find acceptable.

Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate-refractory early rheumatoid arthritis: 2-year results of the register-enriched randomised controlled SWEFOT trial.

OBJECTIVE: To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21 months in patients with methotrexate-refractory early rheumatoid arthritis. METHODS: In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with <1 year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3-4 months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27,487 vs €10,364; adjusted mean difference €16,956 (95% CI 14,647 to 19,162)), while productivity losses did not differ (€33,804 vs €29,220; €3961 (95% CI -3986 to 11,850)), resulting in higher societal cost compared to the conventional group (€61,291 vs €39,584; €20,916 (95% CI 12,800 to 28,660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI -0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2,404,197/QALY from the societal perspective and €1,948,919/QALY from the healthcare perspective. CONCLUSIONS: In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21 months at willingness to pay levels generally considered acceptable. TRIAL REGISTRATION NUMBER: NCT00764725.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

BACKGROUND: Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). METHODS: We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. RESULTS: Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. CONCLUSIONS: We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Fraturas do fêmur proximal no idoso: estudo de custo da doença sob a perspectiva de um hospital público no Rio de Janeiro, Brasil / Hip fractures in the elderly: cost of illness study in a public hospital perspective, Rio de Janeiro, Brazil

O artigo visa a estimar o custo direto médico do tratamento hospitalar de pacientes idosos com fraturas de fêmur proximal, no Hospital Municipal Lourenço Jorge, na cidade do Rio de Janeiro. Estudo observacional, prospectivo, para estimar a utilização de recursos e custos diretos médicos associados à hospitalização por fratura de fêmur proximal em idosos, em 2007 e 2008, sob a perspectiva do prestador de serviços. Foi utilizado um instrumento de coleta de dados através do qual foram registrados recursos identificados na revisão prospectiva dos prontuários. Aos recursos utilizados foram atribuídos custos em reais (R$) baseando-se em valores do ano 2010. Foram realizadas análises descritivas dos custos e utilização de recursos, bem como avaliada a associação de variáveis clínicas e demográficas com o custo final observado. Foram incluídos 82 pacientes, 81,7 por cento do sexo feminino, idade média de 76,96 anos, hospitalização média de 12,66 dias. A mediana de custo por paciente foi de R$ 3.064,76 (IC95 por cento: 2.817,63 a 3.463,98). Hospitalização clínica e procedimento cirúrgico foram responsáveis por 65,61 por cento e 24,94 por cento dos custos, respectivamente. Pacientes submetidos ao tratamento cirúrgico até o quarto dia de hospitalização apresentaram mediana de custos menor do que pacientes submetidos após o quarto dia (R$ 2.136,31 e R$ 3.281,45, p<0,00001). Observou-se também diferença significativa nos custos finais por tipo de procedimento cirúrgico realizado. O custo do tratamento das fraturas de fêmur proximal no idoso foi significativamente maior nos pacientes submetidos à cirurgia após o quarto dia de hospitalização. Hospitalização clínica e procedimento cirúrgico foram os principais componentes do custo final observado.

This paper aims to assess direct medical costs associated to hospital treatment of hip fractures in the elderly in the Municipal Hospital Lourenço Jorge (HMLJ), Rio de Janeiro. Observational, prospective study to assess resource utilization and direct medical costs associated to elderly hip fracture hospitalization in 2007 and 2008, under the health care provider perspective. A standard data collection instrument was used to register identified resources during prospective medical charts review. The resource utilization was converted into Brazilian Real (R$), based on 2010 prices. Descriptive analysis of costs and resource utilization and their association with clinical and demographic variables were performed. Eighty two patients were included, 81.7 percent female, mean age of 76.96 years, hospitalization mean time of 12.66 days. Median total costs per patient were R$ 3,064.76 (IC95 percent: 2,817.63 - 3,463.98). Clinical hospitalization and surgical procedure were responsible for 65.61 percent and 24.94 percent of costs, respectively. Median costs for patients submitted to surgical procedure until the fourth day of hospitalization were lower than median costs for patients submitted after the fourth day (R$ 2,136.45 and R$ 3,281.45, respectively, p<0.00001). A significant difference in average costs per type of surgical procedure was also observed. Cost associated to inpatient treatment of hip fractures in the elderly was higher in patients who performed surgery after the fourth day of hospitalization. Clinical hospitalization and surgical procedure were the main cost components observed.

[Financial cost of early rheumatoid arthritis in the first year of medical attention: three clinical scenarios in a third-tier university hospital in Colombia]. / Costos directos de la artritis reumatoide temprana en el primer año de atención: simulación de tres situaciones clínicas en un hospital universitario de tercer nivel en Colombia.

INTRODUCTION: In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system. OBJECTIVE: The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia. MATERIALS AND METHODS: Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%. CONCLUSIONS: Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.

The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study.

BACKGROUND: Pemphigus vulgaris (PV) represents a potentially life-threatening autoimmune blistering disease in which IgG autoantibodies are directed against cell-cell adhesion molecules. Tumour necrosis factor (TNF)-alpha has been suggested to have a possible role in the mechanism underlying acantholysis. OBJECTIVES: This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV. METHODS: The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regimen except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-alpha levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients. RESULTS: The serum level of TNF-alpha was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-alpha in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2. CONCLUSION: The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-alpha, and this decrease was associated with rapid clinical improvement.

Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combined step-down prednisolone, methotrexate, and sulfasalazine with sulfasalazine alone.

OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

[Markov model of decision making for basic therapy of rheumatoid arthritis: oder of monotherapy and expenses for drug therapy]. / Markovskaia model' priniatiia reshenii pri naznachenii bazisnoi terapii revmatoidnogo artrita: posledovatel'nost' monoterapii i zatraty na lekarstvennuiu terapiiu.

AIM: To design Markov's model of decision making to study the role of order in the use of most usable basic antirheumatic drugs (methotrexate-MT, parenteral gold--PG and sulfasalasine--SS) in terms of the course duration and cost. MATERIAL AND METHODS: The model was based on metaanalysis made in 2000. The program TreeAge 3.0 was used. The prices for the drugs were taken as mean about Moscow for 2002 and prices presented by ACR for 2002. RESULTS: The sequence MT-PG-SS had the advantage over the other sequences in that less number of patients stopped treatment after 5 and 10 years of therapy. Mean cost of the drugs per patient is the lowest (for five years) if MT is prescribed first. In longer treatment SS-MT-PG is more cost-effective. CONCLUSION: It is feasible to design Markov's models for making decision on optimal therapy of rheumatoid arthritis both in terms of cost and clinical response.

A cost effectiveness analysis of treatment options for methotrexate-naive rheumatoid arthritis.

OBJECTIVE: New treatment options for patients with methotrexate (MTX)-naive rheumatoid arthritis (RA) have become available. Given wide variability in efficacy and cost among different treatment options, we sought to determine their relative cost effectiveness to help guide policy in different cost constrained settings. METHODS: We performed a cost effectiveness analysis comparing 5 monotherapy options for patients with MTX-naive RA: (1) etanercept, (2) leflunomide, (3) MTX (up to 15 mg weekly), (4) sulfasalazine (SSZ), and (5) no second line agent. A decision analysis model was used with a time horizon of 6 months. We employed 2 measures of effectiveness based on published clinical trial data: American College of Rheumatology (ACR) 20% response proportion (ACR 20) and a weighted average of proportions achieving ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response, ACR 70WR). Incremental cost effectiveness ratios were calculated as additional cost per patient achieving either outcome, compared with the next most expensive option. RESULTS: In both base case analyses employing ACR 20 and ACR 70WR as effectiveness measures, MTX and SSZ both cost less and were more effective (i.e., cost saving) than no second line agent. Leflunomide cost more and was less efficacious than SSZ (dominated) in analyses using either outcome. The most efficacious option, etanercept, cost US $41,900 per ACR 20 and $40,800 per ACR 70 WR compared with SSZ and MTX, respectively. When we included only direct costs in analyses, the least expensive non-dominated option was SSZ with incremental cost effectiveness ratios of US $900 per ACR 20 and $1500 per ACR 70WR compared with no second line agent. Overall, relative cost effectiveness between MTX and SSZ was sensitive to variation in relevant variables in sensitivity analyses. Otherwise, our extensive sensitivity analyses did not substantially affect the base case results. CONCLUSION: MTX is cost effective (cost saving vs the no second line agent option) for MTX-naive RA in achieving ACR 20 or ACR 70WR over a 6 month period. Based on available data, the relative cost effectiveness between SSZ and MTX cannot be determined with reasonable certainty and SSZ therapy appears to be as cost effective as MTX (cost saving) in achieving ACR outcomes over a 6 month period. The most efficacious option, etanercept, incurs much higher incremental costs per ACR 20 or ACR 70WR than other options analyzed. Whether etanercept compared with MTX is cost effective depends on whether > $40,000 per ACR 20 or ACR 70WR over a 6 month period is considered acceptable.

Impact of leflunomide versus biologic agents on the costs of care for rheumatoid arthritis in a managed care population.

OBJECTIVE: To compare the impact of leflunomide on resource utilization and costs relative to that of etanercept and infliximab among patients with rheumatoid arthritis (RA) in a managed care setting. METHODS: Data were obtained from the PharMetrics Integrated Outcomes Database for all patients newly starting 1 of the 3 medications of interest in 1999 or 2000. Claims were compiled for 180 days prior to the first prescription for study therapy and for a minimum of 90 days thereafter. Measures of interest during follow-up included the incidence of significant interventions (eg, joint injection, synovectomy), 1-year utilization of study therapy, other RA-related medications, inpatient and outpatient services, and total costs of RA-related care. Data were adjusted for variable follow-up using survival techniques. Multivariate analyses were conducted on total costs, controlling for between-group differences in demographic, clinical, and pretreatment characteristics. RESULTS: A total of 4069 patients were included in the study cohort (n = 2217, 1547, and 305 for leflunomide, etanercept, and infliximab, respectively). Three quarters of the cohort were female; etanercept patients were somewhat younger than leflunomide or infliximab recipients. Severity of illness (as measured by the Charlson index) was highest among infliximab patients. The incidence of significant interventions was high in all patients, but did not differ by treatment group. Use of nonsteroidal anti-inflammatory drugs (8.1 versus 8.9 claims) and narcotic analgesics (7.8 versus 8.5) was substantially lower for leflunomide than for etanercept. Costs of RA-related care were 42% to 53% lower among leflunomide patients for biologic medications ($9618 versus $16,534 and $20,263 for etanercept and infliximab, respectively), primarily as a result of lower medication costs. Findings persisted in multivariate analyses of cost. CONCLUSIONS: Leflunomide is associated with reduced costs of medications and other healthcare services relative to biologic medications among managed care patients with RA.