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.     

实施自我管理教育对类风湿关节炎患者的影响

目的:探讨自我管理教育对类风湿关节炎患者治疗作用及预后的影响。方法:对78名类风湿关节炎患者实施自我管理,跟踪随访并与教育前进行比较。结果:接受自我管理教育后的类风湿关节炎患者,教育后患者的自我管理能力增强,自我保健意识提高。结论:自我管理教育的实施,能够提高类风湿关节炎患者的疗效,改善预后,提高生活质量。     

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.     

The economic burden of depression among adults with rheumatoid arthritis in the United States

Aims: Depression is the most frequent comorbidity reported among patients with rheumatoid arthritis (RA). Comorbid depression negatively impacts RA patients’ health-related quality-of-life, physical function, mental function, mortality, and experience of pain and symptom severity. The objective of this study was to assess healthcare utilization, expenditures, and work productivity among patients with RA with or without depression.

Materials and methods: Data from adult patients who had at least two visits each related to RA and depression over a 1-year period were extracted from the Truven Health MarketScan research databases. Outcomes comprised healthcare resource utilization, work productivity loss, and direct healthcare costs comparing patients with RA with depression (n?=?3,478) vs patients with RA without depression (n?=?43,222).

Results: Patients with RA and depression had a significantly greater relative risk of hospitalization and number of all-cause and RA-related hospitalizations, utilization of emergency services, days spent in the hospital, physician visits, and RA-related surgeries compared with RA patients without depression. Patients with RA and depression had a higher risk of and experienced more events and days of short-term disability compared with patients without depression. The incremental adjusted annual all-cause and RA-related direct costs were $8,488 (95% CI = $6,793–$10,223) and $578 (95% CI = –$98–$1,243), respectively, when comparing patients with RA and depression vs RA only.

Limitations: The current analysis is subject to the known limitations of retrospective studies based on administrative claims data.

Conclusions: This study suggested increased healthcare utilization, work productivity loss, and economic burden among RA patients due to comorbid depression. These findings emphasize the importance of managing depression and including depression as a factor when devising treatment algorithms for patients with RA.     

Outcomes of tumor necrosis factor inhibitor cycling versus switching to a disease-modifying anti-rheumatic drug with a new mechanism of action among patients with rheumatoid arthritis

Objectives: To examine treatment patterns, treatment effectiveness, and treatment costs for 1 year after patients with rheumatoid arthritis switched from a tumor necrosis factor inhibitor (TNFi) (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab), either cycling to another TNFi (“TNFi cyclers”) or switching to a new mechanism of action (abatacept, tocilizumab, or tofacitinib) (“new MOA switchers”).

Methods: This retrospective cohort study used administrative claims data for a national insurer. Treatment persistence (without switching again, restarting, or discontinuing), treatment effectiveness (defined below), and costs were assessed for the 12-month post-switch period. Patients were “effectively treated” if they satisfied all six criteria for a treatment effectiveness algorithm (high adherence, no dose increase, no new conventional synthetic disease-modifying anti-rheumatic drug, no subsequent switch in therapy, no new/increased oral glucocorticoids, and <2 glucocorticoid injections). Multivariable logistic models were used to adjust for baseline factors.

Results: The database included 581 new MOA switchers and 935 TNFi cyclers. New MOA switchers were 39% more likely than TNFi cyclers to persist after the switch (odds ratio [OR]?=?1.39; 95% confidence interval [CI]?=?1.12–1.74; p?=?.003) and 36% less likely to switch therapy again (OR?=?0.64; 95% CI?=?0.51–0.81; p?p?=?.006). New MOA switchers had 16% lower drug costs than TNFi cyclers (cost ratio?=?0.84; 95% CI?=?0.79–0.88; p?rheumatoid arthritis-related medical care (cost ratio?=?0.89; 95% CI?=?0.84–0.94; p?Limitations: Claims payments may not reflect rebates or other cost offsets. Medical and pharmacy claims do not include clinical end-points or reasons that lead to new MOA switching vs TNFi cycling.

Conclusions: These results support switching to a new MOA after a patient fails treatment with a TNFi, which is consistent with recent guidelines for the pharmacologic management of established rheumatoid arthritis.     

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.     

A cost-effectiveness and budget impact analysis of apremilast in patients with psoriatic arthritis in Italy

Abstract

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with psoriatic arthritis (PsA), within the Italian National Health Service (NHS).

Methods: A Markov state transition cohort model, which was adapted to the Italian context, was used to compare the costs of the currently available treatments and of the patients’ quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for PsA in Italy, who can be eligible for treatment with apremilast. The eligible population was represented by adult patients with PsA who had an inadequate response to or were intolerant to previous disease-modifying antirheumatic drugs (DMARDs), for the approved indication, and for the treatment studied in the economic analytic model.

Results: This cost-effectiveness analysis estimated that the strategy of using apremilast before biologic therapy is cost-effective, with an incremental cost-effectiveness ratio of €32,263.00 per QALY gained which is slightly over the normal threshold found in other Italian economic studies, which usually considers a 40-year-period. Conversely, the budget impact analysis was conducted over 3?years, and it led to an estimated annual saving of €1.6 million, €4.6 million and €5.5 million in the first, second and third year of apremilast commercialization, respectively, for a total saving of €11.75 million in 3?years.

Limitations: Limitations of this analysis include the absence of head-to-head trials comparing therapies included in the economic model, the lack of comparative long-term data on treatment efficacy, and the assumption of complete independence between the considered response rates to therapy.

Conclusion: The use of apremilast as a first option before the use of biologic agents may represent a cost-effective treatment strategy for patients with PsA who fail to respond to, or are intolerant to, previous DMARD therapy. In addition, based on a budget impact perspective, the use of apremilast may lead to cost savings to the Italian healthcare system.     

A case-control study of anaemia in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs in an adult population in the US: prevalence and impact on healthcare utilisation

Abstract

Objective: The objective of this study was to estimate the prevalence of anaemia and its impact on healthcare utilisation in patients with rheumatoid arthritis (RA).

Methods: Patients with claims for moderate-to-severe RA (ICD-9 code 714.x) treated with disease-modifying antirheumatic drugs as well as controls without RA matched for age, gender and time in plan were selected from the MarketScan Research Database. Anaemia was identified by ICD-9 codes 280.x, 285.2x, 281.9, 285.9 and 284.8. The prevalence ratio and 95% confidence interval (CI) for anaemia among RA patients versus controls were estimated. Overall disease burden was measured using the Elixhauser Comorbidity Index (ECI).

Results: The prevalence ratio for anaemia in RA patients was 2.2 (95% CI 2.1–2.4). Mean ECI was higher in RA (2.26) compared with control (1.02) patients (p<0.001), and RA patients with anaemia had a higher ECI compared with those without anaemia (3.95 vs. 2.08; p<0.001). Total healthcare costs in RA patients with anaemia were approximately twice those of RA patients without anaemia.

Conclusions: The prevalence of clinically diagnosed anaemia in RA patients in the claims database was 2.2 times higher than that in the comparable non-RA control group. RA patients with anaemia had significantly higher levels of co-morbidity and healthcare costs than RA patients without anaemia.     

Inpatient and outpatient rehabilitation for patients with rheumatoid arthritis: a clinical and economic assessment

Summary

The aim of this study was to compare inpatient and outpatient rehabilitation for patients with active rheumatoid arthritis from clinical and cost perspectives.

A single-centre, randomised trial design was used. Data were recorded at baseline, post treatment and at 6 months follow-up. The primary outcome measure was the Arthritis Impact Measurement Scale 2. Several other disease activity, functional and quality of life measures were also assessed (erythrocyte sedimentation rate, C-reactive protein, visual analogue scale for pain, early morning stiffness, tender and swollen joint count, grip strength, timed ‘Up and Go’ test and Schedule for the Evaluation of the Individual Quality of Life—Direct Weighting). All direct and indirect costs were measured. A total of 47 subjects were randomised to the study.

No sustained significant differences were detected between the two groups for the primary or secondary measures at the end of treatment or at follow-up. Total inpatient costs (€81,590) were more than three times higher than total outpatient costs (€25,450).     

The impact of rheumatoid arthritis on the burden of disease in urban China

Abstract

Objectives:

The aim of this study is to assess the burden of disease associated with the impact of rheumatoid arthritis in urban China. Burden of disease is considered from four perspectives: (i) health-related quality-of-life (HRQoL); (ii) health status; (iii) employment status; and (iv) absenteeism and presenteeism.

Methods:

Data are from the 2009 National Health and Wellness Survey (NHWS) of urban China. This is an internet-based survey and details the health experience of 13,007 respondents. The survey is representative of the urban China population at 18 years of age and over (18.1% of the total population). Of those responding to the survey, a total of 353 reported that they had been diagnosed with rheumatoid arthritis – an unweighted estimate of 2.65%. The sample design allows a comparison of those reporting rheumatoid arthritis with those not reporting this disease and, hence, a quantitative assessment of the burden of disease. Estimates of the quantitative impact of the presence of rheumatoid arthritis are through a series of generalized linear regression models. HRQoL is evaluated through the SF-12 instrument together with responses to the first item of the SF-12, self-reported health status. The SF-12 instrument generates three measures of HRQoL: the physical component summary (PCS), the mental component summary (MCS) and SF-6D utilities. Health status is captured as a self-report on a 5-point scale. Employment status is considered in terms of self-reported labor force participation, while absenteeism and presenteeism are estimated from the Work Productivity Activity Index (WPAI). Apart from a binary variable capturing the presence or absence of rheumatoid arthritis, control variables were included to capture the impact of other potential determinants of HRQoL and health status.

Results:

The presence of rheumatoid arthritis in urban China has a significant deficit impact on HRQoL as measured by the PCS and MCS components of the SF-12, SF-6D absolute utilities and on self-assessed health status. In the case of PCS, the deficit impact of rheumatoid arthritis is ?2.289 (95%CI: ?3.042 to ?1.536); for MCS ?1.472 (95%CI: ?2.338 to ?0.605) and for utilities ?0.025 (95% CI: ?0.036 to ?0.014). In the case of health status the odds ratio for the presence of rheumatoid arthritis is 1.275 (95%CI 1.031–1.576). The presence of rheumatoid arthritis has a marked negative effect, just under 8%, on the likelihood of workforce participation. Finally, the presence of rheumatoid arthritis is associated with an increased likelihood of absenteeism and presenteeism.

Limitations:

The NHWS survey has a number of limitations. As the NHWS is an internet-based survey, biases may be present due to the lack of internet penetration in the urban China population. The extent to which individuals and households have internet access is unknown. In addition, the NHWS relies upon respondents reporting they have been diagnosed with one or more specific disease states. These are not, given the nature of the survey, clinically verified. This also introduces a degree of uncertainty. Care should be taken in uncritically generalizing these results to the wider China population.

Conclusions:

The burden of disease associated with self-reported, diagnosed rheumatoid arthritis in urban China is substantial. Utilizing a series of multivariate models, substantial deficits are associated not only in reported HRQoL and health status but also in respect of employment status and, for those in employment, rates of absenteeism and presenteeism.