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.     

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.     

National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans

Objective:

This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.

Methods:

This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005–2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose?>?recommended label dose, (2) average ending dispensed dose?>?maintenance dose, and (3) average dose after maintenance dose?>?maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.

Results:

Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p?p?p?Limitations:

Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ～50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.

Conclusions:

In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.     

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.     

Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States

Abstract

Objective:

To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice.

Methods:

Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink? Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn’s disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included.

Results:

A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs.

Limitations:

This analysis is limited to three TNF-inhibitors and a US managed-care population.

Conclusions:

Based on this analysis of real-world use of TNF-inhibitors among patients in nationwide clinical practice settings, the annual TNF-inhibitor cost per treated patient was lowest for etanercept across all indications.     

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.     

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 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.     

Elicitation of health state utilities associated with differing durations of morning stiffness in rheumatoid arthritis

Abstract

Objective:

Specific symptoms of rheumatoid arthritis (RA), including joint stiffness and functional disability, are most severe in the morning. ‘Morning stiffness’ has a negative impact on health-related quality-of-life (HRQoL); however, how HRQoL is correlated to morning stiffness duration is unknown. The objective of this study was to obtain population-based utility values associated with different durations of morning stiffness in RA.

Design and methods:

The time-trade-off (TTO) approach was used to elicit utility values for four different health states (HS), which differed in morning stiffness duration. One hundred and nine members of the UK general public rated each HS in individual face-to-face interviews with trained investigators. TTO scores were converted into utility values. Visual Analog Scale (VAS) scores were obtained to validate TTO scores.

Results:

On a scale of 0 (death) to 1 (full health), a mean utility value of 0.45?±?0.29 was elicited for ～3?h of morning stiffness (anchor HS), 0.50?±?0.28 for 2–3?h of morning stiffness (HS1), 0.61?±?0.25 for 1–2?h of morning stiffness (HS2) and 0.78?±?0.20 for <1?h of morning stiffness (HS3). The difference between each HS was statistically significant (p?<?0.01). Mean VAS utility scores followed the same trend. Utility incrementally increased with each HS associated with a shorter duration of morning stiffness. Limitations of this research include potential bias from the TTO method due to the discounting effect of time, scale compatibility, and loss aversion.

Conclusions:

The UK population-based utility values show a reduction in morning stiffness duration in RA is associated with improved HRQoL. Despite the impact of morning stiffness on HRQoL, it is rarely evaluated and little is known as to how it is affected by current treatments. The results of this study can be applied in future cost-utility analyses of healthcare interventions which target an improvement in morning stiffness duration for RA patients.     

Adjusting for comorbidities in cost of illness studies

Abstract

Motivation:

Differences in cost of illness (COI) methodological approaches have led to disparate results. This analysis examines two sources of this variation: specification of comorbidities in the estimated cost models and assumed prevalence rates used for generating aggregate costs. The study provides guidance in determining which comorbidities are important to include and how to handle uncertainty in optimal model specification and prevalence rate assumptions.

Methods:

Comorbidities are categorized into four types. Type I comorbidities are those that increase the risk of the disease of interest; Type II comorbidities have no causal link to the disease of interest but are, nonetheless, highly correlated with that disease; Type III comorbidities are illnesses that the disease of interest may cause, and Type IV are comorbidities that have no causal link to the disease of interest and are only weakly correlated with that disease. Two-part models are used to estimate the direct costs of rheumatoid arthritis and diabetes mellitus using 2000–2007 Medical Expenditure Panel Survey data.

Results:

COI estimates are sensitive to the specification of comorbidities. The odds of incurring any expenses varies by 71% for diabetes mellitus and by 27% for rheumatoid arthritis, while conditional expenditures (e.g., expenditures among subjects incurring at least some expenditures) vary by 62% and 45%, respectively. Uncertainty in prevalence rates cause costs to vary. A sensitivity analysis estimated the COI for diabetes ranges from $131.7–$172.0 billion, while rheumatoid arthritis varies from $12.8–$26.2 billion.

Conclusions:

The decision to include Type II and Type III comorbidities is crucial in COI studies. Alternative models should be included with and without the Type III comorbidities to gauge the range of cost effects of the disease. In generating costs, alternative values for prevalence rates should be used and a sensitivity analysis should be performed.     

Cost per patient-year in response using a claims-based algorithm for the 2 years following biologic initiation in patients with rheumatoid arthritis

Abstract

Objective:

To estimate cost per patient-year in response during 2 years following biologic initiation among patients with rheumatoid arthritis (RA).     

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.     

Economic consequences of sequencing biologics in rheumatoid arthritis: a systematic review

Abstract

Background and objectives:

Tumor necrosis factor-alpha (anti-TNF) blocking agents are effective for the treatment of rheumatoid arthritis (RA), with mean response rates of 60–70%. Patients with incomplete response to initial anti-TNF treatment often are switched to other biologic treatments with some success. However, little is known about whether or not switching to anti-TNF or other non-TNF biologic treatments is cost-effective. This study sought to review the economic evidence of sequencing various biologic treatments in RA.

Methods:

A systematic review was conducted of published and unpublished literature (January 2000 to October 2012) on the cost-effectiveness of sequencing biologic treatments in RA after failure of an initial biologic treatment. It included modeling and other economic studies that assessed cost-effectiveness of one or more sequences of biologics. Studies were excluded that evaluated non-biologic sequencing.

Results:

This review of the available evidence suggests that there is limited evidentiary support favoring the cost-effectiveness of switching from one anti-TNF agent to another within the anti-TNF category of biologics. This is due, in large part, to the limited clinical evidence base supporting the incremental efficacy of second- and third-line anti-TNF treatments and to variation on how and when to assess non-response to the first-line biologic. When compared to anti-TNF agents, biologic treatments with a different mechanism of action are more cost-effective as second-line agents.

Limitations:

Not all sequences and patterns of switching, either within or outside of therapeutic class, have been evaluated for clinical benefit and cost-effectiveness, limiting the interpretation of these findings.

Conclusions:

Switching from one anti-TNF agent to another after first-line treatment failure may not be a cost-effective treatment strategy. However, when non-TNF biologics are included in the sequence they are likely to be more cost-effective than anti-TNF specific cycling sequences.     

Tumor necrosis factor blocker dose escalation among biologic naïve rheumatoid arthritis patients in commercial managed-care plans in the 2 years following therapy initiation

Abstract

Objective:

This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab.

Methods:

Non-elderly adult (age 18–65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose.

Results:

A total of 2747 patients met the inclusion criteria (mean age 50 years [SD?=?10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8–1.5% for etanercept, 10.8–12.5% for adalimumab, and 16.4–42.5% for infliximab; ranges at 24 months were 0.8–2.1% for etanercept, 14.3–17.5% for adalimumab, and 26.4–57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p?<?0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions.

Conclusion:

Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.