Assessment of income growth in patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy.

Journal of Medical Economics 1369-6998 doi:10.3111/13696998.2014.925465

Vol. 18, No. 1, 2015, 37–44

Article 0028.R1/925465 All rights reserved: reproduction in whole or part not permitted

Journal of Medical Economics Downloaded from informahealthcare.com by Nyu Medical Center on 05/13/15 For personal use only.

Original article Assessment of income growth in patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy

Martin Bergman

Abstract

Taylor Hospital, Ridley Park, PA, USA

Gourab De Analysis Group, Inc., New York, NY, USA

Objectives: To compare income growth over time between employees with RA treated with anti-TNFs and those treated with methotrexate (MTX).

Arijit Ganguli Global Health Economics and Outcomes Research, AbbVie, IL, USA

James Signorovitch Analysis Group, Inc., Boston, MA, USA

Yanjun Bao Global Health Economics and Outcomes Research, AbbVie, IL, USA Address for correspondence: Dr Martin Bergman, Taylor Hospital, 8 Morton Ave, Suite 304, Ridley Park, PA, USA 19078. [email protected] Keywords: Anti-TNF – Methotrexate – Income – Economic evaluations – Outcomes research – Rheumatoid arthritis Accepted: 14 May 2014; published online: 15 October 2014 Citation: J Med Econ 2015; 18:37–44

Methods: Privately insured employees (aged 18) with 1 RA diagnosis (ICD-9: 714.0) were identified from a large-scale US employer claims database (1998–2011). Patients were stratified into treatment groups (anti-TNF-treated patients and MTX-monotherapy patients) based on their treatment history. The antiTNF-treated patients comprised patients who filled 1 prescription for anti-TNFs, with or without MTX (index date defined as the date of the first anti-TNF prescription). The MTX-treated patients comprised patients who filled 1 prescription for MTX-monotherapy (index date randomly selected). The primary study outcome was the annual income growth rate (US dollars). Patients were followed from their index date to health plan disenrollment or the end of data availability (maximum follow-up of 5 years). The effect of treatment type on income growth was assessed using a multivariable generalized estimating equation model, adjusting for key baseline characteristics. Income growth was compared to that of the general employed population using Social Security data (1998–2011). Results: The regression-adjusted annual growth rate in income for anti-TNF-treated patients (n ¼ 1848) was 2.8% (CI ¼ 1.9–3.6%), significantly greater (p50.05) than the 0.6% (CI ¼ 0.2–1.4%) for MTX-monotherapy patients (n ¼ 1866). Compared to the general employed population, income growth was lower (p50.05) for MTX-monotherapy patients and comparable for anti-TNF-treated patients. Conclusions: Compared to MTX-monotherapy, anti-TNF treatment is associated with a higher income growth rate among employees with RA. Anti-TNF-treated patients experienced comparable income growth to the general employed population norm.

Introduction Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder that has a significant impact on work productivity and maintenance of employment1,2. The onset of RA peaks during working years (ages 40–70)3, which leads to substantial costs for both patients and employers2,4–9. In the US, for example, RA is associated with 4 million work loss days, costing employers a total of $5.8 billion in direct and indirect costs, annually due to sick leave, short- and disability, and workers compensation5. Indirect costs of RA have been estimated ! 2015 Informa UK Ltd www.informahealthcare.com/jme

Income growth with rheumatoid arthritis Bergman et al.

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at $15,934 annually per employee with RA in the US (2006 US dollars), attributable to on-the-job lost productivity (57%), absenteeism/disability (21%), job turnover (21%), and workplace adaptations (51%)8. Although the substantial negative impact of RA on work loss has been well-established, the impacts of RA on career progression have not been fully assessed. Considering current economic conditions in the US, economic policy-makers have put greater emphasis on assessing individual career growth as an indicator of societal prosperity and well-being10,11. Long-term progression of income, defined as compensation paid hourly (wage) or yearly (salary), provides an integrated assessment of the effects of disability, pain, and other RA-related factors that may impact productivity and overall effectiveness in the workplace. Slowed income growth associated with RA would represent a ‘silent’ out-of-pocket cost for patients with RA, as well as a loss to employers and to society. The potential for effective treatments to reduce work loss costs in RA has been demonstrated. Research has demonstrated that anti-tumor necrosis factor (anti-TNF) treatments are associated with improvement in RA disease control as well as control of radiographic progression1,12, and, therefore, can potentially reduce disability, work loss, loss of employment, and subsequent costs for employers1,2. Birnbaum et al.13 demonstrated that patients with RA experienced fewer work loss days and had lower work loss costs in the era following anti-TNF introduction. RA was associated with an additional 25.6 work-loss days in 1997, compared to 20.8 days in 2006 (after anti-TNFs became available). Similarly, work loss costs associated with RA were $2142 in 1997 and were reduced to $1718 in 2006 after anti-TNF availability (both values in 2006 US dollars)13. These results were consistent with an analysis of patients with RA in Germany, where productivity costs for a cohort of patients in 2002 were significantly lower than the productivity costs of a similar cohort in 1997–1998 (E1480 vs E850; p50.05)14. Randomized controlled trials of various anti-TNFs have also demonstrated reductions in functional impairments and improvements in workplace outcomes in patients treated with anti-TNFs15–18. For example, a randomized controlled trial demonstrated that patients treated with anti-TNF combination therapy experienced a significantly lower rate of job loss compared with those patients treated with MTX monotherapy1. These studies demonstrate that use of anti-TNFs may be associated with positive workplace outcomes from both a patient and employer perspective. The current study assesses the potential association between income progression trajectory for RA patients and their treatments. Specifically, this study compares income growth for employees with RA treated with anti-TNFs and those treated with MTX monotherapy. 38


Patients and methods Study sample Actively employed patients with a diagnosis of rheumatoid arthritis (International Classification of diseases, Ninth Edition [ICD-9] code 714.0) were identified from an employer claims database (OptumHealth Reporting and Insights; 1998Q1–2011Q3). This database contains complete medical and prescription drug claims for employees of 27 large, self-insured companies. De-identified demographic information (including income information), monthly eligibility records, and medical/pharmacy claims were available for all selected patients. Patients were required to initiate therapy with either an anti-TNF (including adalimumab, etanercept, infliximab, golimumab, and certolizumab) or MTX. Patients were divided into treatment groups (anti-TNF-treated patients and MTX-monotherapy patients) based on their treatment history. For the anti-TNF cohort, the first prescription date of the anti-TNF therapy was defined as the index date. Patients who were not eligible for anti-TNF cohort were considered for the MTX monotherapy cohort. For the MTX monotherapy cohort, an MTX prescription date was randomly selected and defined as the index date rather than the initiation date of MTX. This is because MTX is typically used as first-line treatment for RA before treatment with anti-TNFs. Consequently, patients, when initiated on MTX, would likely be at a less severe RA disease state than those patients, when initiated on anti-TNFs. Selecting a random MTX prescription date was intended to make the RA disease severity distribution comparable between the treatment cohorts. For the MTX cohort, patients were excluded if they had used an anti-TNF within 6 months prior to or 30 days after the index date19. For both cohorts, patients were required to be 18 years or older on their index date and continuously enrolled in their healthcare plan for at least 6 months prior to the index date. A sub-group of patients from the anti-TNF cohort was further classified as the anti-TNF monotherapy cohort, if they did not have a non-biological disease-modifying anti-rheumatic drug (DMARD) fill within 30 days before or after the index date.

Baseline characteristics Baseline characteristics for the patients in the study sample were summarized during the baseline period 6 months prior to the index date, and included age, gender, geographic region, type of health insurance, index year distribution, Charlson comorbidity index (CCI), annual income at baseline, and RA-related healthcare costs. The CCI is a composite indicator of health status that is made up of 17 medical conditions, each weighted by their predicted www.informahealthcare.com/jme ! 2015 Informa UK Ltd


impact on mortality20. The RA-related healthcare costs consisted of RA-related medical costs and prescription costs. The RA-related medical costs were estimated as the costs of medical claims associated with the ICD-9 code of 714.0x. RA-related prescription costs were obtained as costs for the medications used for RA (see list in Supplemental Table 1). All RA-related costs were inflated to 2011 US dollars using the medical component of the consumer price index (CPI).


Study outcomes The primary study outcome was the annual growth rate in income (US dollars). Employer-reported annualized income (including wage and salary, and excluding variable components such as equity options) available in the healthcare claims record for each patient were used. Patients were followed from their index date to health plan disenrollment or the end of data availability (maximum follow-up of 5 years). The 5-year benchmark was chosen because more than 90% of patients were lost to follow-up after 5 years. Patients with missing income information at the index date were excluded from the analysis.

Statistical analysis The baseline characteristics were compared between the anti-TNF and MTX monotherapy cohorts. Wilcoxon rank-sum tests were used to compare the

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continuous variables, while chi-squared tests were applied for the categorical variables. The long-term income progression between the anti-TNF and MTX monotherapy cohorts were compared using a multivariate regression model. The dependent variable was income from index date up to 5 years of follow-up. Cohort, year, and interaction between year and cohort were used as independent variables. The generalized estimating equation approach was used to account for the within-subject correlation in the income variable over time. The log-link function and gamma distribution were used to address the skewness in the income distribution. In this model, the coefficient corresponding to cohort was an estimate of the difference in income in the index year (defined as the year corresponding to the index date of the subject) between the treatment cohorts, and the coefficient corresponding to interaction was an estimate of the difference in annual rate of growth between the treatment cohorts21. The model was adjusted for index year, age, gender, region, health plan, CCI, and the baseline total RA-related cost (including both medical and prescription costs). p-values 50.05 were considered statistically significant. For comparison, the range of income growth for the general US population was estimated based on the best and worst 5-year runs of national wage data reported by Social Security Average Wage Index (AWI) Statistics during 1998–201122.

Table 1. Differences in baseline characteristics; MTX monotherapy cohort vs anti-TNF cohort.

Baseline characteristics Age Female Region Northeast Midwest South West Unknown Index year 1998–2004 2005–2011 Health insurance plan PPO POS Indemnity Other Annual income at baselinea ($) Charlson Comorbidity Indexb Baseline RA-related total costs RA-related medical costs RA-related prescription costs

MTX monotherapy (n ¼ 1866)

Anti-TNF (n ¼ 1848)

48.43 9.71 1210 (64.8%)

46.15 9.76* 1145 (62.0%)

249 (13.3%) 460 (24.7%) 813 (43.6%) 316 (16.9%) 28 (1.5%)

282 (15.3%)* 421 (22.8%)* 781 (42.3%)* 314 (17.0%)* 50 (2.7%)*

449 (24.1%) 1417 (75.9%)

471 (25.5%) 1377 (74.5%)

1052 (56.4%) 558 (29.9%) 104 (5.6%) 152 (8.1%) 51,554.22 38,004.95 1.10 0.79 1468.53 4002.01 1175.88 3961.48 292.64 551.44

949 (51.4%)* 596 (32.3%)* 129 (7.0%)* 174 (9.4%)* 56,673.92 42,696.83* 1.03 0.93* 3586.02 5552.81* 1120.55 4279.70* 2465.47 3623.94*

* Anti-TNF cohort is significantly different (p50.05) from the MTX monotherapy cohort. a The baseline income was the uninflated income of the patient at index year. b Values are based on medical information from the 6 months leading up to the index date. CCI greater than 1 indicates presence of more than one comorbidity in the past 6 months.

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Figure 1. Sample selection flowchart for patients with rheumatoid arthritis treated with anti-TNF or methotrexate monotherapy.

Results Baseline characteristics Based on the sample selection criteria, 1848 patients were classified into the anti-TNF cohort and 1866 patients were classified into the MTX monotherapy cohort (Figure 1). The baseline comparison between the cohorts is provided in Table 1. Patients in the MTX monotherapy 40


cohort were significantly older (48.4 vs 46.2 years, p50.0001), with a higher comorbidity burden (CCI: 1.1 vs 1.0, p50.0001) compared to the anti-TNF cohort. The average annual income in the index year was lower for the MTX monotherapy cohort ($51,554 vs $56,674, p50.0001) along with significantly lower baseline total RA-related healthcare costs ($1469 vs $3586, p50.0001), compared to the anti-TNF cohort. www.informahealthcare.com/jme ! 2015 Informa UK Ltd



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Figure 2. Observed average annual salary level over time for patients with rheumatoid arthritis treated with anti-TNF or methotrexate monotherapy.

Figure 3. Cumulative regression-adjusted % growth in annual income for patients with rheumatoid arthritis treated with anti-TNF or methotrexate monotherapy.

Income growth The average annual incomes, as observed in the two cohorts over time, are summarized in Figure 2. The observed trend in income progression indicates a higher rate of income growth in the anti-TNF cohort compared to the MTX monotherapy cohort. Figure 3 illustrates the cumulative regression-adjusted yearly rates of income growth from index year, estimated using the multivariate regression model (Table 2), in the two cohorts. On an


average, income for the anti-TNF cohort increased by 2.8% (CI ¼ 1.9%, 3.6%) per year, significantly greater (p50.05) than the 0.6% (CI ¼ 0.2%, 1.4%) per year increase estimated for the MTX monotherapy group. The difference in index year income between the anti-TNF cohort and MTX monotherapy cohort, adjusted for baseline patient characteristics, was $3762. The estimated change from index year after 5 years of follow-up was 3.1% (CI ¼ 0.9%, 7.3%) in the MTX monotherapy cohort as compared to 14.7% (CI ¼ 10.0%, 19.6%) for


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Table 2. Regression model coefficients comparing income progression between MTX monotherapy and anti-TNF cohort.


Model covariatesa

Regression coefficients

Intercept MTX monotherapy cohort Anti-TNF cohort Year Year * MTX monotherapy cohort Year * Anti-TNF cohort Index year Age Region Unknown West South Midwest Northeast Female CCI Health plan Other Indemnity POS PPO Baseline total RA-related healthcare costs

5.54 0.07* – 0.03* 0.02* – 0.00 0.00* 0.41* 0.11* 0.34* 0.28* – 0.35* 0.02 0.09* 0.04 0.01 – 0.00*

*p Values 50.05 considered significant. CCI, Charlson comorbidity index; POS, Point of service plan; PPO, Preferred provider organization. a The dependent variable was income from index date up to 5 years of follow-up. The independent variables were cohort, year, and interaction between year and cohort. The model was adjusted for index year, age, region, gender, CCI, health plan, and baseline total RA-related healthcare costs.

the anti-TNF cohort. The model covariates such as age, region, gender, healthcare plans, and baseline total RA-related healthcare costs were significantly associated with the income progression. Yearly income growth rates for the general US population estimated for the best and worst 5-year runs between 1998–2011 based on Social Security Average Wage Index (SS-AWI) data were 4.0% and 2.1%, respectively22. As displayed in Figure 3, the average growth in income for a patient with RA treated with anti-TNF was consistent with that of the general population. In contrast, the income growth for a patient with RA treated with MTX monotherapy was significantly lower than expected in the general population (p50.05).

Discussion In the real-world setting, patients who initiated anti-TNF therapy were observed to have a significantly higher annual rate of income growth (2.8%), compared to those who received MTX monotherapy (0.6%), even after accounting for differences in patient characteristics and baseline income. Based on these estimated rates and assuming a baseline income of $50,000 (close to the median household income in 2011–2012 based on 42


US census23), patients who initiated anti-TNF therapy were expected to earn an additional $17,063 cumulatively over 5 years, compared to patients who received MTX monotherapy. In the primary analysis, income growth rate of patients treated with anti-TNF therapy, including monotherapy and combination therapy, was compared to the MTX monotherapy cohort. A secondary analysis comparing a sub-group of patients treated with anti-TNF monotherapy only (consisting of anti-TNF treated patients who did not have a non-biological diseasemodifying anti-rheumatic drug fill within 30 days before or after the index date) with patients treated with MTX monotherapy resulted in trends consistent with the primary analysis (Supplemental Figure 1). In our study, the average index year income for patients initiating anti-TNF treatment is observed to be higher than that for patients receiving MTX monotherapy. This may be due to the fact that patients with higher income may have better access to expensive treatment options such as anti-TNF. The objective of the current study was to compare the rate of change in income over years in the two cohorts, irrespective of the income difference in index year. Hence, the study adopted the approach of treating income from all years including the index year as dependent variables and estimating the rate of change in income from index year. This approach has been suggested in previous literature, since such a model incorporates the difference in the baseline outcome between the cohorts while estimating the rate of change21. Income is an important indicator that reflects patients’ level of disability and functional impairment, which may impact the patients’ quality-of-life. In a recent study assessing impact of RA on income, the overall reduction in annual household income in 2002 was estimated to be $6387 and employees with RA had a loss of $3407 (CI ¼ 3209–3604) in their earnings/income that was attributed to RA2. Our study provides a systematic assessment of the impact of treatment choices (i.e., anti-TNF treatment vs MTX monotherapy) on the income potential of patients with RA. Yearly income growth rate for a patient with RA who is treated with an anti-TNF was observed to be within the same range as the general US population. In contrast, income growth for an RA patient treated with MTX was observed to be lower than that expected in the general population. Even though the general population is not directly comparable to our study cohorts, the findings suggest that patients treated with anti-TNFs, including monotherapy, have an income potential consistent with that of the general population norm. Our findings are consistent with previous literature indicating that anti-TNF treatment may be associated with reductions in the burden of RA1,13,14,16. While these therapies are associated with high drug costs compared to MTX monotherapy, their use may be justified www.informahealthcare.com/jme ! 2015 Informa UK Ltd



by cost offsets in other areas. Thus far, these offsets have been demonstrated in direct medical (e.g., hospitalizations) and indirect (i.e., absenteeism/disability) costs13,14. This study adds to the existing literature by demonstrating that the high cost of anti-TNFs may also be partially offset by higher growth in patients’ income over time. There are a few limitations of this study. First, as this was an observational study using administrative claims data, the information available did not necessarily reflect the patient characteristics captured in clinical settings or actual consumption of medication. This limitation is inherent to any study based on administrative claims data. Second, due to the observational nature of the study, it was not possible to adjust the comparisons between the two treatment groups for unobserved differences between the groups. Third, information on patients above the age of 65 was not fully captured in the commercial claims database. Therefore, we only included patients’ observations before the age of 65 in the core analysis. A sensitivity analysis including these observations (data not shown) indicated that this censoring had minimal impact on the results. Fourth, no direct information on differences in severity across the treatment cohorts was available in this data. Instead, CCI and the baseline RA-related medical costs were used as proxy measures for RA severity, and were controlled for in the regression analysis. Lastly, the current study scope was limited to assessing the effect of anti-TNFs on a class level (adalimumab, etanercept, infliximab, golimumab, and certolizumab), when compared with MTX monotherapy. The effect of individual anti-TNF drugs on the income growth can be interesting and of important value for future research consideration.

Conclusions In conclusion, real world evidence suggests that patients with RA who were treated with an anti-TNF had a significantly higher rate of income growth compared to those patients treated with MTX alone. Income growth in anti-TNF treated patients with RA was comparable to the general employed population norm.

Transparency Declaration of funding The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript. Declaration of financial/other relationships Arijit Ganguli and Yanjun Bao are employees of AbbVie and own stock/shares in the company. Martin Bergman is a speaker


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at AbbVie, UCB, and BMS, provides consulting services to AbbVie, BMS, J&J, Amgen, and Genentech, and owns stocks/ shares in J&J. Gourab De was an employee of Analysis Group, Inc. at the time of this research, and James Signorovitch is an employee of Analysis Group, Inc., which received consulting fees from AbbVie for this research. Acknowledgments The authors would like to acknowledge Min Yang, Sneha Kelkar, and Melissa Diener, employees of Analysis Group, Inc., for their contribution in drafting the manuscript.

References 1. Bejarano V, Quinn M, Conaghan PG, et al. Effect of the early use of the antitumor necrosis factor adalimumab on the prevention of job loss in patients with early rheumatoid arthritis. Arthritis Rheum 2008;59:1467-74 2. Wolfe F, Michaud K, Choi HK, et al. Household income and earnings losses among 6396 persons with rheumatoid arthritis. J Rheumatol 2005;32:1875-83 3. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med 2011;365:2205-19 4. Michaud K, Messer J, Choi HK, et al. Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-year study of 7527 patients. Arthritis Rheum 2003;48:2750-62 5. Kleinman NL, Cifaldi MA, Smeeding JE, et al. Annual incremental health benefit costs and absenteeism among employees with and without rheumatoid arthritis. J Occup Environ Med 2013;55:240-4 6. Simons WR, Rosenblatt LC, Trivedi DN. The economic consequences of rheumatoid arthritis: analysis of Medical Expenditure Panel Survey 2004, 2005, and 2006 data. J Occup Environ Med 2012;54:48-55 7. Ozminkowski RJ, Burton WN, Goetzel RZ, et al. The impact of rheumatoid arthritis on medical expenditures, absenteeism, and short-term disability benefits. J Occup Environ Med 2006;48:135-48 8. Birnbaum H, Pike C, Kaufman R, et al. Employer model of workplace impacts of anti-TNF therapy for rheumatoid arthritis. J Occup Environ Med 2009;51:1167-76 9. Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin 2010;26:77-90 10. Mishel L, Shierholz H. A decade of flat wages: the key barrier to shared prosperity and a rising middle class [Internet]. 2013. Economic Policy Institute (EPI). Washington, DC. http://s1.epi.org/files/2013/BP365.pdf. Accessed October 23, 2013 11. Sacks DW, Stevenson B, Wolfers J. Subjective well-being, income, economic development and growth [Internet]. 2010. The National Bureau of Economic Research (NBER). Cambridge, MA. http://www.nber.org/papers/w16441.pdf. Accessed October 23, 2013 12. Chen Y, Jobanputra P, Barton P, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Heal Technol Assess 2006;10:iii-iv, xi-xiii, 1-229 13. Birnbaum HG, Pike C, Banerjee R, et al. Changes in utilization and costs for patients with rheumatoid arthritis, 1997 to 2006. Pharmacoeconomics 2012;30:323-36 14. Kirchhoff T, Ruof J, Mittendorf T, et al. Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and cost savings. Rheumatology (Oxford) 2011;50:756-61 15. Birnbaum H, Shi L, Pike C, et al. Workplace impacts of anti-TNF therapies in rheumatoid arthritis. Expert Opin Pharmacother 2009;10:255-69 16. Halpern MT, Cifaldi MA, Kvien TK. Impact of adalimumab on work participation in rheumatoid arthritis: comparison of an open-label extension study and a registry-based control group. Ann Rheum Dis 2009;68:930-7


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20.

21. 22. 23.

treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625-39 Romano PS, Roos LL JJ. Adapting a clinical comorbidity index for use with ICD-9-CM administrative data: differing perspectives. J Clin Epidemiol 1993;46:1075-9 Fitzmaurice G, Laird N, Ware J. Applied Longitudinal Analysis. Hoboken, New Jersey: John Wiley & Sons;2004 Social Security Administration. Average Wage Index. http://www.ssa.gov/ oact/cola/awidevelop.html. Accessed September 21, 2013 US Census. Income, poverty, and health insurance coverage in the United States: 2012. 2013. United States Census Bureau. https://www.census.gov/ hhes/www/hlthins/data/incpovhlth. Accessed October 23, 2013


17. Kavanaugh A, Fleischmann R, Emery P, et al. Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis 2013;72:64-71 18. Keystone EC, van der Heijde D, Kavanaugh A, et al. Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis. J Rheumatol 2013;40:1487-97 19. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the

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Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis.

Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy.

Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis.

Mortality in patients with rheumatoid arthritis-associated interstitial lung disease treated with an anti-tumor necrosis factor agent.

Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

Determinants associated with work participation in patients with established rheumatoid arthritis taking tumor necrosis factor inhibitors.

Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab.

Tumour necrosis factor in serum and synovial fluid of patients with active and severe rheumatoid arthritis.

Drug survival rates of tumor necrosis factor inhibitors in patients with rheumatoid arthritis and ankylosing spondylitis.

Prolactin increases tumor necrosis factor alpha expression in peripheral CD14 monocytes of patients with rheumatoid arthritis.

Prolonged remission of marginal zone lymphoma in a patient with rheumatoid arthritis treated with anti-tumor necrosis factor agents.

The comparative effectiveness of abatacept versus anti-tumour necrosis factor switching for rheumatoid arthritis patients previously treated with an anti-tumour necrosis factor.

ANCA-positive crescentic glomerulonephritis in a patient with rheumatoid arthritis treated with anti-tumor necrosis factor alpha.

Disease activity improvement in rheumatoid arthritis treated with tumor necrosis factor-α inhibitors correlates with increased soluble Fas levels.

Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy.

Staphylococcus lugdunensis septic arthritis and epidural abscess in a patient with rheumatoid arthritis receiving anti-tumour necrosis factor therapy.

Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study.

Remaining Pain in Early Rheumatoid Arthritis Patients Treated With Methotrexate.

Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα.

Development of Rheumatoid Nodules after Anti-Tumor Necrosis Factor-α Treatment with Adalimumab for Rheumatoid Arthritis.

Assessment of the Effect of Methotrexate Therapy on Bone Metabolism in Patients with Rheumatoid Arthritis.

Longer durations of antitumour necrosis factor treatment are associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis.

Tumor necrosis factor alpha is associated with disease activity and the degree of anemia in patients with rheumatoid arthritis.

Effects of Concomitant Methotrexate on Large Joint Replacement in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors: A Multicenter Retrospective Cohort Study in Japan.