Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden.

AIMS: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

[Off-label therapy of rheumatoid arthritis and spondyloarthritis]. / Off-Label-Therapie bei rheumatoider Arthritis und Spondyloarthritiden.

For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a large number of approved medications are available. Nevertheless, in Germany even for these diseases several off-label risks exist for the rheumatologist prescribing antirheumatic drugs which have recently led to a series of recourses or threats of recourse. In RA as well as SpA first of all biologicals are the target of recourse imposed mainly by health insurances. In RA monotherapy (when labeled only in combination with methotrexate), combination with leflunomide (instead of methotrexate) and dose deviations are the most important causes. In SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe peripheral spondyloarthritis including enthesitis which does not exactly meet the diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In these cases, however, based on successful randomized controlled trials and changed diagnostic criteria a label extension is expected in the near future. Until then it seems suitable to apply for permission for this treatment from insurers in each case.

[Economic analysis of parecoxib in the management of postsurgical pain in gynecology]. / Análisis económico de parecoxib en el tratamiento del dolor postoperatorio en ginecología.

BACKGROUND: Poorly managed postoperative pain has a negative impact in healing patients and costs of care. METHODS: A model to estimate economic and health consequences of parecoxib 40 mg and morphine 12 mg regarding ketorolac 30 mg, on the management of postoperative pain in gynecologic laparotomy surgery from the perspective of the Mexican Social Security Institute (IMSS) was developed. A systematic review to identify the proportion of patients that rated their analgesic treatment as "excellent" or "good" in the Patient Global Evaluation of Study Medication, 12 hours after administration of the analgesic (responders), was performed. The patients who rated "fair" or "poor" their treatment were administered additional 4 mg of morphine. Costs in the model correspond to the acquisition costs of analgesics in which the institution would incur. RESULTS: The proportion and cost per responder were: morphine: 14.44% and $192.79, ketorolac: 32.44% and $34.82, parecoxib: 35.51% and $121.25.Treatment with morphine was more expensive and less effective than both, ketorolac and parecoxib, while the cost per additional percent point of responders with parecoxib (compared to ketorolac) was $28.15. For the management of postoperative pain, ketorolac and parecoxib are more effective and less expensive than morphine, additionally parecoxib would be an alternative for patients with contraindication to ketorolac use. CONCLUSION: The management of postoperative pain with parecoxib is more effective and, in the context of IMSS, less expensive than morphine, also constitutes an alternative with a reasonable incremental cost compared to ketorolac.

Treatment strategies aiming at remission in early rheumatoid arthritis patients: starting with methotrexate monotherapy is cost-effective.

OBJECTIVE: To perform a modelling study on the cost-effectiveness of three outcome-directed strategies in early RA patients: Strategy 1: starting MTX monotherapy, followed by the addition of LEF, followed by MTX with addition of anti-TNF; Strategy 2: start with MTX and LEF combination followed by MTX with anti-TNF; and Strategy 3: immediate start with MTX and anti-TNF. METHODS: A validated Markov model was used to evaluate the cost-effectiveness of the three strategies. Effectiveness of the strategies was determined using daily practice data from two cohorts and used as input parameter in the model. Patients treated according to the strategies were matched for baseline 28-joint DAS (DAS-28). Using Monte Carlo simulation, expected costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained for a 5-year time horizon were calculated following both a health-care and a societal perspective. RESULTS: The percentage of patients in remission and number of QALYs were comparable between the three strategies. Starting with a combination (MTX plus LEF or anti-TNF) was more costly than starting with MTX alone. This resulted in an unfavourable incremental cost-effectiveness ratio for starting on anti-TNF vs initially MTX: health-care perspective of €138,028 and from a societal perspective of €136,150 per QALY gained over 5 years. CONCLUSION: In this modelling study, starting with MTX or anti-TNF has comparable effectiveness. However, initial anti-TNF was far more expensive than starting with MTX monotherapy. Therefore, based on this study, a treatment strategy starting with MTX monotherapy is favoured over a strategy with MTX and anti-TNF right away in early RA patients.

Analysis of gaps in feline ectoparasiticide purchases from veterinary clinics in the United States.

BACKGROUND: The study objective was to examine cat owner ectoparasiticide purchases in the United States and estimate the impact of purchase gaps on timely ectoparasite protection administration. These purchase gaps lead to periods of time when cats are unprotected from ectoparasites. METHODS: Ectoparasiticide purchase transactions for individual cats from 671 U.S. veterinary clinics from January 1, 2017 through June 30, 2019 were evaluated to determine time "gaps" between doses of ectoparasiticides purchased in a defined 12-month period. Ectoparasiticides examined were topically applied products that contained fluralaner, fipronil/(S)-methoprene/pyriproxyfen, imidacloprid/pyriproxyfen or selamectin as active ingredients. The duration of protection following administration of one dose was 8-12 weeks for the fluralaner-containing product and one month for the other products. RESULTS: Ectoparasiticide purchase records were obtained from 114,853 cat owners and analysis found that most owners bought ≤ 6 months of protection during the year, with 61-75% (depending on the product) purchasing just 1-3 months of protection. The size of the average purchase gap was determined for all dose combinations out to 12 months of protection (5-7 doses for fluralaner and 12 doses for the other three products dosed monthly. The largest gaps occurred between the first and second doses and the second and third doses. Average purchase gaps for the four different products between doses 1 and 2 ranged from 11.2 to 13.9 weeks and between doses 2 and 3 ranged from 7.7 to 12.2 weeks. The fraction of purchases separated by gaps and the average length of the gap tended to decrease with increasing number of doses purchased. Owners purchasing the 8 to 12-week duration product containing fluralaner provided ectoparasite protection ("doses plus gap period") for a larger proportion of each 2-dose period compared with owners purchasing products administered monthly. CONCLUSIONS: When cat owners purchase flea and tick medication, gaps between subsequent purchases reduces the proportion of time ectoparasite protection can be provided. The duration of the gap between doses has an impact on the effectiveness of flea/tick medication because it inserts a period without flea and tick protection between doses of flea and tick medication. The gaps between purchases were shorter and the period of ectoparasite protection was larger for owners purchasing a 12-week product than for owners purchasing a monthly product.

Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication.

OBJECTIVE: To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. DATA SOURCES: A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term 'paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. STUDY SELECTION: All available reports of studies were identified. Product labelling provided additional information. DATA EXTRACTION: Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. DATA SYNTHESIS: Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose-response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4-7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. CONCLUSIONS: Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use.

Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes.

PURPOSE: Although antiepileptic drugs (AEDs) with multisource generic alternatives are becoming more prevalent, no case-control studies have been published examining multisource medication use and epilepsy-related outcomes. This study evaluated the association between inpatient/emergency epilepsy care and the occurrence of a recent switch in AED formulation. METHODS: A case-control analysis was conducted utilizing the Ingenix LabRx Database. Eligible patients were 12-64 years of age, received >or=145 days of AEDs in the preindex period, had continuous eligibility for 6 months preindex, and no prior inpatient/emergency care. Cases received care between 7/1/2006 and 12/31/2006 in an ambulance, emergency room, or inpatient hospital with a primary epilepsy diagnosis. Controls had a primary epilepsy diagnosis in a physician's office during the same period. The index date was the earliest occurrence of care in each respective setting. Cases and controls were matched 1:3 by epilepsy diagnosis and age. Odds of a switch between "A-rated" AEDs within 6 months prior to index were calculated. RESULTS: Cases (n = 416) had 81% greater odds of having had an A-rated AED formulation switch [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.25 to 2.63] relative to controls (n = 1248). There were no significant differences between groups regarding demographics or diagnosis. Significant differences were found with regard to medical coverage type (case Medicaid = 4.6%, control Medicaid = 1.8%, p = 0.002). Post hoc analysis results excluding Medicaid recipients remained significant and concordant with the original analysis. DISCUSSION: This analysis found an association between patients receiving epilepsy care in an emergency or inpatient setting and the recent occurrence of AED formulation switching involving A-rated generics.

Leflunomide use in New Zealand. A national prospective post-marketing study.

BACKGROUND: This post-marketing study aimed to record rates of retention, adverse effects and efficacy of leflunomide in the treatment of rheumatoid arthritis (RA). The secondary objectives were to make a semi-quantitative assessment of response to treatment and to examine the effect of a loading dose on adverse events and treatment duration. METHODS: Rheumatologists in New Zealand contributed to a prospective leflunomide treatment registry. Baseline data were collected on leflunomide initiation and information about treatment experience was sought every 6 months. Each patient was followed for 2 years. Kaplan-Meier analysis was used to evaluate differences in stopping rates between lack of efficacy and adverse effects. Hazard analysis was used to evaluate the effect of using a loading dose on retention rate. RESULTS: Three hundred and eight patients were enrolled in the study; complete follow-up data were available for 244 patients. Retention of patients on leflunomide was 64% at 12 months and 49.4% at 2 years. Reasons for stopping were adverse events (54 patients), loss of effect (25 patients) and miscellaneous reasons (14 patients). Use of a loading dose had no effect on retention; there was no difference in treatment duration between those who stopped from adverse effects or loss of efficacy. CONCLUSION: Leflunomide was effective in treating RA in a group that had longer duration of disease and greater prior use of disease-modifying agents than the groups studied in clinical trials. Rates of withdrawal were lower than those reported in other post-marketing studies, but were higher than those from phase III clinical trials.

Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.

BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare but life-threatening condition that is characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right-sided heart failure and frequently death. Orally administered agents used for the treatment of symptomatic, moderate-to-severe PAH include sildenafil and the endothelin (ET) receptor antagonists (ERAs), bosentan and sitaxentan (sitaxsentan). Ambrisentan is a new oral ET(A) receptor-selective ERA, with higher ET receptor affinity than bosentan. Placebo-controlled, randomized clinical trials (RCTs) have demonstrated that ambrisentan (5 or 10 mg/day) is safe and effective. To provide health economic data on the multiple oral PAH therapies currently available, a population-based cost-minimization analysis (CMA) was conducted for Canada. METHODS: The primary requirement for a CMA is that all clinical outcomes be equivalent between comparator treatments. To provide such supporting data, a literature search was conducted for RCTs of oral agents used to treat symptomatic PAH. This was followed by application of direct and indirect statistical methods to support the hypothesis of clinical equivalence between the oral agents. Estimates for PAH prevalence, incidence and death rates were then used to build a population-based CMA model. The base-case analysis considered costs for drug therapy, outpatient pharmacy costs, medical consultations and visits, laboratory and diagnostic procedures and other healthcare-related resources. In addition, costs for secondary pharmacotherapy in cases where the primary agent had to be discontinued because of adverse effects were also included. The time horizon for evaluating pharmacotherapy was 3 years, all costs were in 2008 Canadian dollars ($Can) and the costs were discounted at a rate of 3% annually. The study perspective was the Canadian healthcare system. RESULTS: There were no double-blind RCTs comparing ambrisentan with any of the other oral agents. Therefore, an indirect comparison of placebo-controlled trials of PAH drugs had to be used to support the clinical equivalence. This included a calculation of standardized mean differences (SMD) between agents (vs placebo) and a meta-regression analysis on the primary and secondary trial endpoints. Keeping in mind the caveats associated with indirect trial comparisons, the data suggested similar clinical efficacy over 12-16 weeks between agents, as indicated by the identical magnitude of the SMD between the active agent and placebo and the non-significant differences between drugs as determined by the meta-regression analysis. The population-based model projected that the number of PAH patients clinically suitable for these drugs in Canada would be 931 in the first full-budget year (i.e. 2009) with an increase to 1114 by the third full year. The CMA revealed the following rank order of the least to most costly agent; sildenafil, ambrisentan, sitaxentan and bosentan. Sildenafil was the least costly, primarily because of the lower daily drug-acquisition cost. Of the three ERAs, ambrisentan would be associated with annual cost savings of $Can3.4 and $Can5.6 million when used as an alternative to sitaxentan or bosentan, respectively. CONCLUSIONS: Ambrisentan is less costly than other available ERAs, including bosentan and sitaxentan, but is more costly than sildenafil. In PAH patients in whom an ERA is the preferred agent, ambrisentan may be the drug of choice because of its economic advantages and improved safety profile.

[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.

[Cost of rheumatoid arthritis in france: comparison leflunomide/etanercept]. / Coût de la polyarthrite rhumatoïde en France: comparaison léflunomide/étanercept.

Treatment of rheumatoid arthritis was deeply modified with the availability since 1999 of anti-TNFalpha. The clinical superiority of these drugs compared to traditional treatments is proven, but can one make the assumption that the cost of these innovative treatments is partially compensated by a reduction of consumption of other health resources? A retrospective observational study was carried out in the Midi-Pyrenees area, from the point of view of health insurance, to compare the consumed health resources between two cohorts of patients, one treated by etanercept (Enbrel) and the other by leflunomide (Arava). Two hundred and fifty three patients were included in the etanercept cohort and 539 in the leflunomide cohort. The average annual PR cost for a patient treated with etanercept is 13 936 euro and 5 764 euro for a patient treated with leflunomide. The health costs avoided by recourse to etanercept do not compensate the high cost of this drug.

Zonisamide: new drug. No advantage in refractory partial epilepsy.

(1) The first-line treatment for patients with partial epilepsy is carbamazepine monotherapy. Second-line options include monotherapy with valproic acid, gabapentin, lamotrigine or oxcarbazepine. Other antiepileptics are also available for combination therapy of refractory partial epilepsy. (2) Zonisamide is a sulphonamide derivative that inhibits carbonic anhydrase; it resembles topiramate, a drug already approved for use for this indication in the European Union. (3) The main clinical trial, a double-blind study lasting 36 weeks, compared the addition of zonisamide or placebo to ongoing treatment in 351 patients with refractory partial epilepsy. The "response rate" (the proportion of patients with at least a 50% reduction in the frequency of seizures) was significantly higher with zonisamide plus the previous treatment than with placebo plus the previous treatment (46.6% versus 17.6%). An indirect comparison suggests that this is no better than treatment with a second-line antiepileptic drug. (4) Results of three other placebo-controlled trials of third-line combinations in a total of 499 patients treated for 12 weeks were similar. (5) The main adverse effects of zonisamide are those typically seen with topiramate: neuropsychological disorders and disorders due to carbonic anhydrase inhibition (kidney stones, reduced perspiration, and hyperthermia). There are various other adverse effects, including a risk of severe skin rash. (6) The profile of interactions is complex. There is a risk of pharmacokinetic interactions, and of pharmacodynamic interactions with other carbonic anhydrase inhibitors. (7) In France, treatment with zonisamide costs nearly 20 times more than treatment with carbamazepine or valproic acid. (8) Zonisamide has no therapeutic advantages over other antiepileptics available for combination therapy of partial epilepsy.

[Economic evaluation of a new treatment for rheumatoid arthritis].

In recent years, new biologic agents have been approved for the treatment of rheumatoid arthritis. These agents may yield clear clinical benefits but impose greater costs than standard treatment. Economic evaluations have been used to provide evidence for the cost-effectiveness of treatment. We described two approaches to the cost-effectiveness analysis of the treatment of rheumatoid arthritis-micro-level economic evaluation based on quality-adjusted life years (QALYs) and macro-level economic evaluation based on disability-adjusted life years (DALYs).

Cost-effectiveness Analysis of Treatment Sequence Initiating With Etanercept Compared With Leflunomide in Rheumatoid Arthritis: Impact of Reduced Etanercept Cost With Patent Expiration in South Korea.

PURPOSE: In south Korea, the price of biologics has been decreasing owing to patent expiration and the availability of biosimilars. This study evaluated the cost-effectiveness of a treatment strategy initiated with etanercept (ETN) compared with leflunomide (LFN) after a 30% reduction in the medication cost of ETN in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). METHODS: A cohort-based Markov model was designed to evaluate the lifetime cost-effectiveness of treatment sequence initiated with ETN (A) compared with 2 sequences initiated with LFN: LFN-ETN sequence (B) and LFN sequence (C). Patients transited through the treatment sequences, which consisted of sequential biologics and palliative therapy, based on American College of Rheumatology (ACR) responses and the probability of discontinuation. A systematic literature review and a network meta-analysis were conducted to estimate ACR responses to ETN and LFN. Utility was estimated by mapping an equation for converting the Health Assessment Questionnaire-Disability Index score to utility weight. The costs comprised medications, outpatient visits, administration, dispensing, monitoring, palliative therapy, and treatment for adverse events. A subanalysis was conducted to identify the influence of the ETN price reduction compared with the unreduced price, and sensitivity analyses explored the uncertainty of model parameters and assumptions. FINDINGS: The ETN sequence (A) was associated with higher costs and a gain in quality-adjusted life years (QALYs) compared with both sequences initiated with LFN (B, C) throughout the lifetime of patients with RA and MTX-IR. The incremental cost-effectiveness ratio (ICER) for strategy A versus B was ₩13,965,825 (US$1726) per QALY and that for strategy A versus C was ₩9,587,983 (US$8050) per QALY. The results indicated that strategy A was cost-effective based on the commonly cited ICER threshold of ₩20,000,000 (US$16,793) per QALY in South Korea. The robustness of the base-case analysis was confirmed using sensitivity analyses. When the unreduced medication cost of ETN was applied in a subanalysis, the ICER for strategy A versus B was ₩20,909,572 (US$17,556) per QALY and that for strategy A versus C was ₩22,334,713 (US$18,753) per QALY. IMPLICATIONS: This study indicated that a treatment strategy initiated with ETN was more cost-effective in patients with active RA and MTX-IR than 2 sequences initiated with LFN. The results also indicate that the reduced price of ETN affected the cost-effectiveness associated with its earlier use.

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide for rheumatoid arthritis in Germany: II. The contribution of leflunomide to efficiency.

OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND RESULTS: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide in rheumatoid arthritis in Germany: I. Selected DMARDs and patient-related costs.

OBJECTIVE: To quantify direct costs of medication and cost of illness (according to functional capacity) for patients with rheumatoid arthritis (RA) in Germany, allowing further use in a health economic evaluation of sequential therapy with disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using a modelling approach, which was based on secondary analysis of existing data and on data from a sample of 583 patients from the German rheumatological database of 1998. Functional capacity was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs were calculated from resources utilised and patients' work capacity. Direct costs consisted of outpatient medical services, inpatient treatment, long-term care and rehabilitation treatment. Indirect costs incurred by sick leave and premature retirement were quantified according to the human-capital approach. MAIN OUTCOME MEASURES AND RESULTS: Average total direct costs (year 1998-2001 values) per patient per year for continuous treatment with the selected DMARDs comprising costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1 approximately equal to $US 0.91; average of the period from 2000 through 2001)] followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for RA-related non-DMARD medication of euro 554 per patient, including management of ADRs. Mean cost of illness (year 1998 values) excluding medication cost amounted to euro 17,868 per RA patient per year. Annual costs increased with increasing disability, i.e. decreasing functional capacity, of RA patients from euro 6029 per patient with more than 94% of functional capacity to euro 28,509 per patient with <20% of functional capacity. In general, there was a predominance of indirect costs in each of the categories of functional capacity, ranging between 74% and 87% of total (direct and indirect) annual costs per RA patient. Annual direct costs increased from euro 811 to euro 7438 per patient with increasing disability. Inpatient treatment was the predominant component of direct costs. Patients in the worst category (<20%) of function experienced hospital costs that were 6.5 times higher than those of patients in the best category (>94%). CONCLUSIONS: On the basis of the data presented it can be concluded that the results of this investigation are typical for patients in rheumatological care in Germany and can therefore be used in a health economic analysis of different DMARD sequences aimed at changing disease progression over time.

Leflunomide: new indication. In psoriatic rheumatism: too many risks, too little efficacy.

(1) The severity of joint involvement in psoriatic rheumatism varies greatly and its outcome is difficult to predict; some patients have long-term spontaneous remissions. The best-evaluated slow-acting treatments are sulfasalazine and methotrexate; adding etanercept can help some patients who do not respond to these drugs. (2) Leflunomide, an immunosuppressant drug, is already marketed for the treatment of rheumatoid arthritis, a condition for which it shows a less favourable risk-benefit balance than methotrexate. (3) Leflunomide is now licensed in France for "active psoriatic rheumatism". (4) The only available clinical data come from a double-blind placebo-controlled trial in 190 patients. On the basis of a combined outcome measure, significantly more patients responded to leflunomide than to placebo (59% versus 29.7%). However, the patients' global assessment was less positive: 15.8% of patients felt their condition had deteriorated during leflunomide therapy, compared to 24.2% of patients in the placebo group. The study population was too heterogeneous to show which types of patients might benefit most from leflunomide therapy. (5) Pharmacovigilance studies have confirmed some severe adverse effects (hepatic, cutaneous and haematological) and have uncovered other previously unrecognised effects such as interstitial pneumonia, hypertension, weight loss, and peripheral neuropathies. (6) In France, leflunomide treatment costs nearly 10 times more than methotrexate. (7) We conclude that leflunomide should not be used to treat psoriatic rheumatism.

Comparison of rehospitalization rates and associated costs among patients with schizophrenia receiving paliperidone palmitate or oral antipsychotics.

PURPOSE: Comparative data on rehospitalization patterns and associated institutional costs after inpatient treatment with paliperidone palmitate or oral antipsychotic therapy are reported. METHODS: A retrospective cohort study was conducted using discharge and billing records from a large hospital database. Selected clinical and cost outcomes were compared in a cohort of adult patients who received the long-acting antipsychotic paliperidone palmitate during a schizophrenia-related index hospital stay and a cohort of patients who received oral antipsychotic therapy during their index admission. Inverse probability-of-treatment weights based on propensity scores were used to reduce confounding. Rates of all-cause and schizophrenia-related rehospitalization and emergency room (ER) use in the two cohorts over periods of up to 12 months were analyzed using a multivariate Cox proportional hazard model. Institutional costs for the evaluated postdischarge events were compared via multivariate linear regression analysis. RESULTS: In the first 12 months after index hospital discharge, the risk of all-cause rehospitalization and ER use was significantly lower in the paliperidone palmitate cohort than in the oral antipsychotic cohort (hazard ratio, 0.61; 95% confidence interval [CI], 0.59-0.63; p < 0.0001); institutional costs during the first 6 months after discharge were significantly lower in the paliperidone palmitate cohort than in the comparator group (adjusted mean monthly cost difference -$404; 95% CI, -$781 to -$148; p < 0.0001). CONCLUSION: The use of paliperidone palmitate therapy during patients' index hospital admission for schizophrenia was associated with a reduced risk of hospital readmission or ER use and lower postdischarge institutional costs.