Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy

Abstract

Objective:

This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer’s perspective in Italy.

Methods:

An individual patient simulation model was used to project lifetime medical costs (payer’s perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis.

Results:

Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient’s lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY.

Conclusion:

The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.     

Medication adherence and persistence in the treatment of rheumatoid arthritis with adalimumab and etanercept. Six years of analysis

Objective:

The aim of this study was to evaluate medication adherence and persistence of patients treated with Etanercept and Adalimumab for Rheumatoid Arthritis, also giving economic evaluations on therapy costs for Received Daily Dose (RDD).

Materials and methods:

This retrospective study took into account 6 years from January 1, 2007 to December 31, 2012. Medication adherence was quantified utilizing the ratio between RDD and Prescribed Daily Dose (PDD). Persistence has been reckoned taking into account the actual days of therapy comparing posology with supplied dose. The persistence has been graphed according to Kaplan-Meier method. The cost per RDD was reckoned starting from the expense incurred by Pescara General Hospital.

Results:

Medication adherence gave results in values between 0.88–0.97 for Etanercept and 0.83–0.90 for Adalimumab. The value of persistence was 100% for Etanercept and 90% for Adalimumab for the first year, and 70% for Etanercept and 80% for Adalimumab for the second year. In the 3rd year the persistence for Etanercept was 50% while for Adalimumab it was 60%. In the fourth year the persistence for Etanercept was 21% while for Adalimumab it was 27%. The statistical analysis was conducted using the Log rank test. The average cost per RDD was €32.97 for Etanercept and for Adalimumab it was €32.00 as an average of 6 years.

Conclusion:

The medication adherence was good for both Etanercept and Adalimumab. The rate of persistence decreased strictly in the fourth year of treatment. This data suggests the need for continuous monitoring of patients in treatment with TNF blockers.     

Key data elements for use in cost-utility modeling of biological treatments for rheumatoid arthritis

Abstract

Objectives:

Economic evaluation is becoming more common and important as new biologic therapies for rheumatoid arthritis (RA) are developed. While much has been published about how to design cost-utility models for RA to conduct these evaluations, less has been written about the sources of data populating those models. The goal is to review the literature and to provide recommendations for future data collection efforts.     

Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan

Aims: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis investigated the cost-effectiveness of the second-line treatment with tofacitinib, compared with adalimumab, both plus methotrexate (MTX), in patients with moderate-to-severe RA and an inadequate response to the first-line MTX, from a Taiwan National Health Insurance Administration perspective.

Materials and methods: A patient-level simulation model was used to project lifetime costs and quality-adjusted life-years (QALYs). Base-case analysis compared second-line treatment with tofacitinib 5?mg twice daily plus MTX vs adalimumab 40?mg every 2?weeks plus MTX. Patients switched or discontinued treatment due to a lack or loss of effectiveness or a serious adverse event. Efficacy was measured by change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score. HAQ-DI scores were used to predict mortality and resource utilization, and were mapped onto utility values to estimate QALYs. Efficacy and safety data were derived from clinical trials and other secondary sources. Uncertainty in model parameters was explored using one-way deterministic and probabilistic sensitivity analyses.

Results: Patients gained 0.09 more QALYs with second-line tofacitinib plus MTX compared with adalimumab plus MTX (5.13 vs 5.04, respectively) at an additional cost of New Taiwan Dollars (NT$) 12,881. The incremental cost-effectiveness ratio was NT$143,122/QALY. One-way sensitivity analysis confirmed the base-case result was robust.

Limitations: The lack of available clinical data, particularly for HAQ-DI scores, may introduce some bias in the analysis. No patients were in an early stage of RA, which may limit the generalizability of these results. Base-case results from our study are not necessarily generalizable to countries with healthcare systems that differ considerably from Taiwan.

Conclusions: From a payer perspective, second-line treatment with tofacitinib plus MTX is a cost-effective treatment strategy, compared with adalimumab plus MTX, in patients with moderate-to-severe RA in Taiwan.

Trial registration: ClinicalTrials.gov identifier: NCT00853385.     

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators

Aims: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs.

Materials and methods: An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY.

Results: For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ～$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs.

Conclusions: bDMARD treatment sequences are cost-effective from a US societal perspective.     

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

Abstract

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.     

Annual acquisition and administration cost of biologic response modifiers per patient with rheumatoid arthritis,psoriasis, psoriatic arthritis,or ankylosing spondylitis

Abstract

Objective:

To estimate annual biologic response modifier (BRM) cost per treated patient with rheumatoid arthritis, psoriasis, psoriatic arthritis, and/or ankylosing spondylitis receiving etanercept, abatacept, adalimumab, certolizumab, golimumab, infliximab, rituximab, or ustekinumab.

Methods:

This was a cohort study of 69,349 commercially insured individuals in a nationwide claims database with one of these conditions that had a claim for one of these BRMs between January 2008 and December 2010 (the index BRM/index date). Cost per treated patient was calculated as the total BRM acquisition and administration cost to the payer in the first year after the index date (including costs of other BRMs after switching) divided by the number of patients who received the index BRM. Etanercept was selected as the reference for comparisons.

Results:

Etanercept was the most commonly used index BRM (n?=?32,298; 47%), followed by adalimumab (n?=?20,582; 30%), infliximab (n?=?11,157; 16%), abatacept (n?=?2633; 4%), rituximab (n?=?1359; 2%), golimumab (n?=?687; <1%), ustekinumab (n?=?388; <1%), and certolizumab (n?=?245; <1%). Using etanercept as the reference, the cost per treated patient in the first year across all four conditions was 102% for adalimumab and 108% for infliximab. Newer BRMs had costs relative to etanercept that were 90% to 102% for rheumatoid arthritis, 132% for psoriasis, 100% for psoriatic arthritis, and 94% for ankylosing spondylitis.

Limitations:

Potential study limitations were the lack of clinical information (e.g., disease severity, treatment outcomes) or indirect costs, the inability to compare costs of newer BRMs across all four conditions, and much smaller sample sizes for newer BRMs.

Conclusions:

Of the BRMs that are approved for indications within all four conditions studied, etanercept had the lowest cost per treated patient when assessed across all four conditions.     

Indirect cost-effectiveness analyses of abatacept and rituximab in patients with moderate-to-severe rheumatoid arthritis in the United States

Abstract

Objective: To estimate the incremental cost per quality-adjusted life-years (QALYs) for abatacept and rituximab, in combination with methotrexate, relative to methotrexate alone in patients with active rheumatoid arthritis (RA).

Methods: A patient-level simulation model was used to depict the progression of functional disability over the lifetimes of women aged 55–64 years with active RA and inadequate response to a tumor necrosis factor (TNF)-α antagonist therapy. Future health-state utilities and medical care costs were based on projected values of the Health Assessment Questionnaire Disability Index (HAQ-DI). Patients were assumed to receive abatacept or rituximab in combination with methotrexate until death or therapy discontinuation due to lack of efficacy or adverse events. HAQ-DI improvement at month 6, after adjustments for control drug (methotrexate) response, was derived from two clinical trials. Costs of medical care and biologic drugs, discounted at 3% annually, were from the perspective of a US third-party payer and expressed in 2007 US dollars.

Results: Relative to methotrexate alone, abatacept/methotrexate and rituximab/methotrexate therapies were estimated to yield an average of 1.25 and 1.10 additional QALYs per patient, at mean incremental costs of $58,989 and $60,380, respectively. The incremental cost-utility ratio relative to methotrexate was $47,191 (95% CI $44,810–49,920) per QALY gained for abatacept/methotrexate and $54,891 (95% CI $52,274–58,073) per QALY gained for rituximab/methotrexate. At an acceptability threshold of $50,000 per QALY, the probability of cost effectiveness was 90% for abatacept and 0.0% for rituximab.

Conclusion: Abatacept was estimated to be more cost effective than rituximab for use in RA from a US third-party payer perspective. However, head-to-head clinical trials and long-term observational data are needed to confirm these findings.     

Derivation of severity index for rheumatoid arthritis and its association with healthcare outcomes

Abstract

Objectives:

To develop a claims-based severity index for rheumatoid arthritis (RA) using the Veterans Health Administration (VHA) database.

Methods:

Adult patients with at least two RA diagnoses 2 months apart were identified between 10/1/2008–09/30/2009. Patients were required to have at least 12 months continuous health plan enrollment before and after the index date (first RA diagnosis date) for an overall study period of 10/1/2007–09/30/2010. A severity index for rheumatoid arthritis (SIFRA, a proprietary algorithm of SIMR, Inc. [STATinMED Research]) was developed by calculating a weighted sum of 34 RA-related indicators assessed by an expert Delphi panel of six rheumatologists, including laboratory, clinical, and functional status, extra-articular manifestations, surgical history, and medications, during a 1-year pre-index period. Separate SIFRA versions were derived for patients with and without laboratory information. Correlations between SIFRA and previously validated claims-based indexes for RA severity (CIRAS), and other traditional comorbidity indexes were calculated during the pre-index period. The relationship between SIFRA and follow-up healthcare outcomes was also examined using histograms.

Results:

The Spearman’s rank correlations between SIFRA and CIRAS were 0.525 for SIFRA without and 0.539 with laboratory data. The correlations between SIFRA and the Charlson Comorbidity Index (CCI) (0.1503 without, 0.1135 with laboratory data), Elixhauser Index (ELIX) (0.105 without, 0.079 with laboratory data), and Chronic Disease Score (CDS) (0.255 without, 0.239 with laboratory data) were low. Histograms showed that patients in the upper tercile of SIFRA incurred $9123 more all-cause and $1326 more RA-related healthcare costs during the 1-year post-index period than patients in the lower tercile. Using SIFRA in combination with CCI, CDS, or ELIX significantly increased the percentage of variation explained in outcomes measures.

Limitations:

Patients in the VHA database may not represent typical RA patients since the database generally contains older, economically disadvantaged men with a high disease burden. Validity of the score is indirectly based on disease activity score 28 (DAS28), which measures disease activity rather than severity.

Conclusions:

SIFRA was found to have moderate correlations with the previously validated CIRAS score, and demonstrated evidence of being a significant determinant of total and RA-related healthcare costs for RA patients. This study suggests that SIFRA could be an important methodological tool to control for severity in RA-related outcomes research. The algorithm can be applied to any claims dataset.     

Use of a validated algorithm to estimate the annual cost of effective biologic treatment for rheumatoid arthritis

Objectives:

To estimate biologic cost per effectively treated patient with rheumatoid arthritis (RA) using a claims-based algorithm for effectiveness.

Methods:

Patients with RA aged 18–63 years in the IMS PharMetrics Plus database were categorized as effectively treated if they met all six criteria: (1) a medication possession ratio ≥80% (subcutaneous) or at least as many infusions as specified in US labeling (intravenous); (2) no biologic dose increase; (3) no biologic switch; (4) no new non-biologic disease-modifying anti-rheumatic drug; (5) no new or increased oral glucocorticoid; and (6) ≤1 glucocorticoid injection. Biologic cost per effectively treated patient was defined as total cost of the index biologic (drug plus intravenous administration) divided by the number of patients categorized by the algorithm as effectively treated. Similar methods were used for the index biologic in the second year and for a second biologic after a switch.

Results:

Rates that the index biologic was categorized as effective in the first year were 31.0% etanercept (2243/7247), 28.6% adalimumab (1426/4991), 28.6% abatacept (332/1160), 27.2% golimumab (71/261), and 20.2% infliximab (474/2352). Mean biologic cost per effectively treated patient, per the algorithm, was $50,141 etanercept, $53,386 golimumab, $56,942 adalimumab, $73,516 abatacept, and $114,089 infliximab. Biologic cost per effectively treated patient, using this algorithm, was lower for patients who continued the index biologic in the second year and higher after switching.

Conclusions:

When a claims-based algorithm was applied to a large commercial claims database, etanercept was categorized as the most effective and had the lowest estimated 1-year biologic cost per effectively treated patient. This proxy for effectiveness from claims databases was validated against a clinical effectiveness scale, but analyses of the second year or the year after a biologic switch were not included in the validation. Costs of other medications were not included in cost calculations.     

Comparative evaluation of treatment patterns and healthcare utilization of newly-diagnosed rheumatoid arthritis patients by anti-cyclic citrullinated peptide antibody status

Background: Anti-cyclic citrullinated peptide (CCP) antibody positivity is an established diagnostic factor for severe disease activity and joint damage and a prognostic factor for aggressive disease in rheumatoid arthritis (RA).

Objective: To compare RA-related treatment, healthcare utilization, and joint erosion between anti-CCP-positive and anti-CCP-negative RA patients.

Methods: Newly-diagnosed RA patients were identified from the Henry Ford Health System database between January 1, 2009 and December 31, 2014; the date of the first RA diagnosis within the study period was the index date. Baseline anti-CCP test was used to categorize patients as anti-CCP-positive or anti-CCP-negative, and outcomes were evaluated in the 6 months post-index.

Results: There were 217 anti-CCP-positive and 191 anti-CCP-negative RA patients included in the study. A higher proportion of anti-CCP-positive patients were initiated on RA treatment than anti-CCP-negative patients (70.5% vs 23.0%; p?<?.0001). More anti-CCP-positive patients received methotrexate (73.2% vs 56.8%; p?=?.0374), while more anti-CCP-negative patients received hydroxychloroquine (31.8% vs 13.1%; p?=?.0037) in first-line therapy. A higher proportion of anti-CCP-negative patients were tested for rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). Of those tested, there were more positive test results in the anti-CCP-positive cohort compared to the anti-CCP-negative cohort (RF: 84.4% vs 18.2%, p?<?.0001; C-reactive protein [CRP]: 69.7% vs 48.3%, p?=?.0008; and ESR: 89.5% vs 53.9%, p?<?.0001). Outpatient utilization predominated, with more anti-CCP-positive patients having any outpatient physician office visit (96.3% vs 77.5%, p?<?.0001) and a higher mean number of visits (5.3 vs 2.5, p?<?.0001) than anti-CCP-negative patients. Among anti-CCP-positive (n?=?113) and anti-CCP-negative (n?=?58) patients with imaging results, more anti-CCP-positive patients had joint erosion compared to anti-CCP-negative patients (18.6% vs 8.6%; p?=?.0858); however, statistical significance was not reached.

Conclusion: RA patients with positive anti-CCP antibodies had higher degrees of inflammation and disease activity as indicated by laboratory results, which likely contributed to their higher rates of healthcare utilization, joint erosion, and proportions of RA treatment.     

A real-world,multi-site,observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab

Objectives: To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction.

Methods: An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher’s exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction.

Results: One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p?=?.0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p?<?.0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p?<?.0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p?<?.0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p?<?.0001) and total visit time (p?=?.0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time.

Limitations: Findings may not be representative of care delivery for all RA infusion practices or RA patients.

Conclusions: Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.     

The potential value of rapid,cloud-enabled onsite testing for the diagnosis of rheumatoid arthritis in the United States

Abstract

Aims: Improvements in information technology have granted the recent development of rapid, cloud-enabled, onsite laboratory testing for rheumatoid arthritis (RA). This study aims to quantify the value to payers of such technologies.

Materials and methods: To calculate the value of rapid, cloud-enabled, onsite laboratory testing to diagnose RA relative to traditional, centralized laboratory testing, an Excel-based decision tree model was created that simulated potential cost-savings to payers who cover routine evaluations of RA patients in the US. First, a conceptual framework was created to identify the value components of rapid, cloud-enabled onsite testing. Second, value associated with patient time savings, savings on visit fees, change in treatment costs, and QALY improvements was measured, leveraging existing literature and information from an observational study. Lastly, these value components were combined to estimate the total incremental value accruing to payers per patient-year relative to centralized laboratory testing.

Results: Rapid, cloud-enabled, onsite testing is estimated to save one office and 1.81 laboratory visits during the evaluation period for the average patient. Results from an observational study found that rapid, cloud-enabled testing increased the likelihood of completing diagnostic orders from 84.5% to 97%, resulting in an increased probability of early treatment (3.5 percentage points) with disease-modifying anti-rheumatic drugs among patients eligible for treatment. The combined total value was $5,648 per evaluated patient-year. This value is primarily attributed to health benefits of early treatment ($5,048), fewer visit payments ($459), and patient time savings due to fewer office ($216) and laboratory visits ($255).

Limitations and conclusions: Data on the impact of rapid, cloud-enabled, onsite testing on patient health, care delivery, and clinical decision-making is scarce. More robust real-world data would confirm the validity of our model. Rapid, cloud-enabled, onsite testing has the potential to generate significant value to payers.     

Cost-effectiveness analysis of oxycodone with naloxone versus oxycodone alone for the management of moderate-to-severe pain in patients with opioid-induced constipation in Canada

Background:

Approximately 20–30% of Canadians suffer from chronic pain. Guidelines for the management of chronic pain support the use of controlled-release (CR) opioids to treat chronic pain. Although effective in managing chronic pain, oxycodone is associated with high rates of opioid-induced constipation (OIC). The cost-effectiveness of a combination of oxycodone for the management of pain and naloxone for the relief of OIC has not previously been evaluated for Canada.

Methods:

A decision analytic model was developed to estimate the cost-utility of combination oxycodone/naloxone compared to oxycodone alone in four populations. Drug costs for managing pain and healthcare costs related to managing OIC were included in the analysis and the primary measure of effectiveness was quality adjusted life years (QALYs) derived from OIC rates observed in clinical trials. The analysis was conducted from a healthcare system perspective, used a 1-year time horizon, and results were expressed in 2015 Canadian dollars.

Results:

In all four patient populations, there was a trade-off between slightly higher total expected costs for Targin treated patients compared to oxycodone treated patients, but also improved clinical benefits in terms of reduced OIC, which resulted in higher QALYs for patients. Although analgesic costs were found to be slightly higher for Targin treated patients, Targin also resulted in cost offsets to the healthcare system in terms of less rescue laxative drug use and other resources required for the management of OIC. The resulting 1-year cost-utility of Targin compared to oxycodone ranged from $2178–$7732 per QALY gained in the base case analysis, and it was found that these cost-utility results remained robust and at low values throughout a series of one-way deterministic analyses of uncertainty.

Conclusion:

The clinical effectiveness of oxycodone/naloxone in managing pain and OIC compared to CR oxycodone alone resulted in low cost-utility estimates.     

Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population

Aims: To examine the comorbidity and economic burden among moderate-to-severe psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of Defense (DoD) population.

Materials and methods: This retrospective cohort claims analysis was conducted using DoD data from November 2010 to October 2015. Adult patients with ≥2 diagnoses of PsO and/or PsA (cases) were identified, and the first diagnosis date from November 2011 to October 2014 was defined as the index date. Patients were considered moderate-to-severe if they had ≥1 non-topical systemic therapy or phototherapy during the 12 months pre- or 1 month post-index date. Patients without a PsO/PsA diagnosis during the study period (controls) were matched to cases on a 10:1 ratio based on age, sex, region, and index year; the index date was randomly selected. One-to-one propensity score matching (PSM) was conducted to compare study outcomes in the first year post-index date, including healthcare resource utilization (HRU), costs, and comorbidity incidence.

Results: A total of 7,249 cases and 72,490 controls were identified. The mean age was 48.1 years. After PSM, comorbidity incidence was higher among cases, namely dyslipidemia (18.3% vs 13.5%, p?<?.001), hypertension (13.8% vs 8.7%, p?<?.001), and obesity (8.8% vs 6.1%, p?<?.001). Case patients had significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p?<?.0016), ambulatory ($8,804 vs 4,642; p?<?.001), emergency room ($432 vs $350; p?<?.001), pharmacy ($6,878 vs $1,160; p?<?.001), and total healthcare costs ($18,311 vs $7,795; p?<?.001).

Limitations: Claims data are collected for payment purposes; therefore, such data may have limitations for clinical research.

Conclusions: During follow-up, DoD patients with moderate-to-severe PsO and/or PsA experienced significantly higher HRU, cost, and comorbidity burden.     

Modeling of the clinical and economic impact of a risk-sharing agreement supporting a treat-to-target strategy in the management of patients with rheumatoid arthritis in France

Objectives: To evaluate the cost-effectiveness of a Treat-to-Target strategy with certolizumab pegol in patients with rheumatoid arthritis in the context of a pay-for-performance agreement in which medication costs are refunded in case of discontinuation during the first 3 months of treatment.

Methods: The Treat-to-Target strategy consisted of a systematic switch to second-line tumor necrosis factor (TNF)α inhibitor in case of an unmet ACR50 response at 3 months compared to current routine clinical practice. A reference cohort treated first-line with certolizumab pegol according to current practice without systematic switching was considered as the comparator. A decision-tree model was constructed to estimate clinical outcome (health assessment questionnaire-disability index or HAQ-DI score), time spent in ACR50 response (ACR 50), and direct costs of treatment over a 2-year period. HAQ scores were derived from American College of Rheumatology 50 (ACR50) responses. All TNFα inhibitors were assumed to have equivalent efficacy and tolerability. Costs were estimated at 2013 French retail prices (date of the pay-for-performance agreement).

Results: The mean duration of an ACR50 response was 1.23 years in the Treat-to-Target strategy certolizumab pegol cohort vs 0.98 years in the reference cohort, resulting in a mean gain in HAQ at 24 months of 0.117. The Treat-to-Target strategy with a mix of TNFα inhibitors as second-line therapy was more expensive than the reference strategy in absolute terms, but this difference was entirely offset by the pay-for-performance agreement. The Treat-to-Target strategy was, thus, cost-neutral over a 2-year period after the payback of CZP cost for patients not achieving the target at 3 months.

Conclusions: In the context of a pay-for-performance agreement, the management of patients with rheumatoid arthritis using a Treat-to-Target strategy with certolizumab pegol in first line is dominant compared to standard use of this drug in the French setting in 2013.     

Cost-utility of celecoxib use in different treatment strategies for osteoarthritis and rheumatoid arthritis from the Quebec healthcare system perspective

Abstract

Objective: To assess the cost-utility of celecoxib in three treatment strategies for arthritis in Quebec, considering both upper gastrointestinal (GI) and cardiovascular (CV) events.

Methods: A Markov analytic framework was used to model patients with osteoarthritis and rheumatoid arthritis at low/average and high risk of GI and CV toxicity over 5 years with monthly cycles. Treatment strategies were modelled in line with Canadian clinical practice. In first-line treatment, patients started on celecoxib; second-line, patients started on a non-selective non-steroidal anti-inflammatory drug (NSAID) and switched to celecoxib after a first GI event; third-line, patients started on a non-selective NSAID, added a proton pump inhibitor (PPI) after a first GI event, and switched to celecoxib after a second GI event (while maintaining the PPI). Model inputs were determined through comprehensive literature searches (MEDLINE and EMBASE) from 1995 to 2006. Included studies evaluated GI (dyspepsia, uncomplicated and complicated ulcers, death) and CV (myocardial infarction, stroke, death) events. Drug and procedure costs were derived from Canadian published sources (Can$2005).

Results: Total costs per patient for celecoxib first-, second-, and third-line treatment were Can$4,790, $3,390, and $3,466, and total quality-adjusted life-years (QALY) were 3.251, 3.231, and 3.230, respectively. In all risk categories, celecoxib second-line was less costly and as effective as celecoxib third-line, producing savings to the healthcare system. Although celecoxib first-line generated incremental expenditures versus celecoxib second-line, it was also more effective. The resulting cost-utility ratio for the high-risk population was Can$54,696/QALY. Based on this analytical approach, a treatment strategy where celecoxib is used before the combination of a non-selective NSAID plus a PPI possesses cost advantages for the Quebec provincial drug programme. One-way sensitivity analysis (varying GI and CV event rates, utilities, and cost) generally showed second-line treatment with celecoxib as the dominant strategy compared with third-line treatment with celecoxib.

Conclusion: Although effectiveness of second- and third-line celecoxib use is similar, total cost is lower for second-line. These results suggest that the use of celecoxib before the combination of a non-selective NSAID plus a PPI is relatively cost-effective in the treatment of arthritis pain and support the full benefit listing of celecoxib in Quebec's drug programme.