Impact of Etanercept on Work and Activity Impairment in Employed Moderate to Severe Rheumatoid Arthritis Patients in the United States


McKesson Specialty, 1 Concorde Gate, 4th Floor, Toronto, Ontario M3C 3N6 Canada. E-mail:



To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA).


This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test.


RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233–22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001).


In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment.


Work disability, common in patients with rheumatoid arthritis (RA), frequently occurs soon after diagnosis and increases with disease progression ([1-4]). For those continuing employment, functional disability associated with RA means increasing levels of absenteeism and change in employment ([1, 5, 6]). Disability, absenteeism, and change in job status therefore all contribute to extensive RA-related productivity losses ([1, 2]). However, one of the largest contributors to the productivity burden of RA may be reduced productivity at work, or presenteeism, of patients who continue to work but cannot work to their full capacity ([7, 8]).

RA-related productivity loss has a considerable impact on patients and society, which is made even more relevant by the fact that most patients with RA are of working age at disease onset ([2, 9]). An estimate of the annual economic burden of RA in the US puts the societal impact at $19.3 billion (in 2005), with 56.5% ($10.9 billion) due to indirect costs, 18.3% of which results from excess disability/absenteeism and presenteeism of employed individuals with RA ([10]).

Evidence from studies in the literature suggests that treatment with the tumor necrosis factor (TNF) antagonists etanercept ([8, 11, 12]), adalimumab ([13, 14]), infliximab ([15]), and certolizumab pegol ([16]) increases productivity, allows patients with RA to continue employment for longer periods, and reduces the degree of RA-related absenteeism. A significant attenuation of absenteeism with etanercept plus methotrexate combination therapy was observed in patients with early active RA in the UK ([8]). In addition, etanercept therapy was associated with significant reductions in absenteeism and improvements in productivity among employed US patients with moderate to severe RA, which partially or completely offset the cost of treatment ([12]).

While studies have identified productivity gains with TNF antagonist treatment, the challenge remains in translating these productivity gains accurately into economic benefits for employers and how these gains affect their return on investment. The Work Productivity and Activity Impairment Questionnaire (WPAI) was designed to quantify productivity as well as impairments in daily activities and is validated for many diseases, including RA ([17-19]). The WPAI can discriminate between patients with varying degrees of functional disability, making it a suitable instrument to measure a change in status in working RA patients after initiation of etanercept ([19]). In this study, we evaluated the effectiveness of etanercept therapy on work productivity outcomes in employed patients. Because RA-associated impairments also occur outside the work place, this study also examined the effect of etanercept therapy on domestic productivity and satisfaction.

Box 1. Significance & Innovations

  • Rheumatoid arthritis (RA) is associated with significant losses in productivity through increased absenteeism (missed time from work) and presenteeism (impairment at work) in employed patients with RA, which can have a negative financial impact on employers.
  • Using the RA-specific Work Productivity and Activity Impairment Questionnaire to assess productivity, patients with RA experienced significant improvements in overall work impairment, absenteeism, presenteeism, and activity impairment at work within 6 months of initiating etanercept. Significant improvements in domestic activities over the same period were also observed.
  • Gains in work productivity partially or completely offset the annual cost of etanercept in patients.


Study population and design

This study was a prospective, multicenter, observational, longitudinal study of US employed individuals diagnosed with moderate to severe RA. The primary objective was to assess the change in the WPAI measures of absenteeism, presenteeism, overall work impairment, and activity impairment after 6 months of etanercept treatment. The secondary objectives were to estimate the change in WPAI measures with etanercept at 1, 2, and 3 months; to estimate the monetary impact from improvements in work productivity; and to quantify the impact of etanercept treatment on domestic productivity from baseline to month 6.

Patients were recruited from US rheumatology centers between January 29, 2009 and March 5, 2010. All eligible patients were between the ages of 18 and 70 years, were employed full or part time for at least 3 months prior to starting etanercept, had no plans to retire in the next 6 months, were candidates for treatment with biologic agents, had been prescribed etanercept for moderate to severe RA per US prescribing information in the course of routine care, and were scheduled to begin etanercept therapy within 1 month of providing informed consent. Patients who were employed for <5 hours per week, did not speak English, were disabled or receiving long-term disability benefits, or had received TNF antagonist therapy prior to the baseline interview were excluded. No formal evaluations to determine disease severity were required to be used by the investigators in order to evaluate real-world conditions. Patients were provided a small stipend for participation in each interview. The study was approved by a central independent review board (Independent Review Consulting, San Anselmo, California) and all patients provided written informed consent prior to participation.

Data collection

Before or on the same day as the first etanercept administration, each patient was contacted by telephone to complete a baseline survey that assessed employment status and occupation (profession), RA disease history, demographic characteristics, current health status, the responses to the RA-specific WPAI (WPAI-RA) ([19]), and a domestic activity questionnaire.

The WPAI-RA consists of 6 questions assessing the ability to work and perform regular activities during the past 7 days. The results produce the following 4 scores: 1) absenteeism (work time missed), 2) presenteeism (impairment at work), 3) work productivity loss (overall work impairment), and 4) activity impairment. Scores are expressed as percentages, with a higher percentage indicating greater impairment and less productivity. A version of this questionnaire that was validated for telephone administration was requested and the version supplied by the developer was used for data collection in this study.

The domestic activity questionnaire asks questions about the activities involved in maintaining a home, such as shopping, food preparation, cleaning, and other household chores. The questionnaire contains 5 questions relating to 1) the number of days missed from domestic activities over the past month because of RA, 2) the hours missed from domestic activities over the past week because of RA, 3) the number of hours normally spent each week on domestic activities, 4) the degree to which RA affected domestic productivity over the past week (assessed on a 0–100 scale, where 0 = not at all productive and 100 = fully productive), and 5) an assessment of satisfaction with domestic productivity using a 5-point Likert scale, with potential responses ranging from “not at all satisfied” to “completely satisfied”; this scale also allows a not applicable response option. Overall domestic productivity is calculated in terms of responses to questions 1 through 4, as in the following equation: [(Q3 − Q2) × Q4]/Q3 × 100. Higher percentages indicate fewer hours missed from domestic activities and/or increased productivity during domestic activities.

Patient occupations were categorized using criteria defined by the US Bureau of Labor Statistics ([20]). For patients who were not lost to followup, subsequent telephone interviews were conducted at 1, 2, 3, and 6 months postinitiation of etanercept, even if patients discontinued etanercept. The surveys administered during these telephone followups collected information on current health status, changes in work status since the last interview, whether patients were still taking etanercept and if not, why they had stopped, and responses to the WPAI-RA and domestic productivity questionnaires. Interview consistency was addressed primarily through limiting the number of interviewers and through activity, discussion, and application training techniques.

Medical chart reviews of all patients were conducted following the completion of the 6-month telephone interview. Data on the timing of and reasons for switching from etanercept to another RA treatment were collected for those who switched within the 6-month treatment period.

Statistical analysis

Previous studies have reported discontinuation rates of ∼20–30% for TNF blockers due to primary nonresponse ([21-24]); therefore, this study was a priori powered to allow for 30% of patients to discontinue therapy (targeting 140 patients to complete 6 months of therapy). The statistical analyses were based on intent-to-treat principles and all enrolled patients were included in the primary analysis. In the primary analysis, no missing data imputations were conducted and improvement between assessments was based on reported values at each time point. The significance of change in individual work impairment parameters from baseline to months 1, 2, 3, and 6 was assessed using Wilcoxon's signed rank test (primary method for testing). To assess the impact of missing data, an analysis on the change in work impairment was also conducted using mixed models for repeated measures. The mixed model tests were secondary and were used to conduct a sensitivity analysis against Wilcoxon's tests; similar results between the mixed model and Wilcoxon's tests supported the use of the latter tests without imputation for missing data, conducted at a 5% significance level. A linear regression analysis was used to identify baseline characteristics that were predictors of improvement in WPAI-RA parameters over the 6-month treatment period for all patients. Statistical analyses were conducted using SAS, version 9.2.

The annual costs of reduced productivity based on WPAI-RA responses were estimated using methods similar to those described in previous studies ([25-28]). To quantify the economic impact, total hours lost over the 6-month treatment period per patient were calculated by determining the area under the curve of plots of hours lost due to RA for absenteeism and presenteeism at all time points from baseline. The extension of hours lost from baseline through 6 months provided a measure of the expected productivity losses in the absence of etanercept (i.e., hours lost over 7 days at baseline × 24 weeks, assuming no further productivity loss in the following 24 weeks); the difference in the 2 calculations (productivity in the presence and absence of etanercept) provided the hours gained (or lost) through etanercept treatment. The data were extrapolated to 12 months and total hours were converted to costs using the human capital approach through multiplying hours lost by average salary estimates based on patient-reported job categories ([12, 25]). Wage estimates by job category were obtained from the US Bureau of Labor Statistics using wages from 2009 ([29]). The net impact of increased work productivity (gains from reduced absenteeism and presenteeism combined) through treatment was estimated by subtracting the annual cost of etanercept from productivity gains. Etanercept cost was based on the 2009 wholesale acquisition cost of $194.13 per 25 mg (annual equivalent of $20,190) ([30]).



A total of 204 patients were recruited from 55 rheumatology centers across the US. The mean ± SD age was 46.6 ± 10.9 years, 72% were women, and 44% were at minimum college graduates (Table 1). Most patients (84%) were employed full time and the most common professions were managerial or professional positions (39%); the mean ± SD time at the current job was 10.5 ± 9.9 years and 17% reported a prior change of job because of RA. The most common RA treatment at baseline was methotrexate (31%).

Table 1. Baseline patient characteristics*
CharacteristicAll patients (n = 204)Continuers (n = 153)Discontinuers (n = 51)Pa
  1. RA = rheumatoid arthritis; NSAIDs = nonsteroidal antiinflammatory drugs.
  2. aP values relate to the comparison of parameters for continuer and discontinuer patients.
Age, mean ± SD (range) years46.6 ± 10.9 (20–67)46.7 ± 10.9 (22–67)46.3 ± 10.9 (20–64)0.84
Women, no. (%)147 (72)107 (70)40 (80)< 0.0001
Race, no. (%)   < 0.0001
White167 (82)129 (84)38 (76) 
Hispanic/Latino18 (9)11 (7)7 (14) 
African American12 (6)8 (5)4 (8) 
Other6 (3)5 (3)1 (2) 
Education, no. (%)   < 0.0001
Less than college114 (56)83 (54)31 (62) 
College graduate and above89 (44)70 (46)19 (38) 
Annual family income, no. (%)   0.30
<$30,00043 (22)31 (21)12 (25) 
$30,000 to <$60,00056 (29)39 (26)17 (35) 
$60,000 to <$90,00042 (21)36 (24)6 (13) 
≥$90,00055 (28)42 (28)13 (27) 
Employment status, no. (%)   < 0.0001
Full time170 (84)130 (85)40 (80) 
Part time33 (16)23 (15)10 (20) 
Occupation, no. (%)   < 0.0001
Managerial/professional specialty79 (39)59 (39)20 (40) 
Technical, sales, and administrative65 (32)51 (33)14 (28) 
Service34 (17)24 (16)10 (20) 
Other25 (12)19 (12)6 (12) 
Time at current job, mean ± SD (range) months125.8 ± 118.4 (3–492)130.4 ± 123.2 (3–492)111.8 ± 102.1 (3–348)0.34
Change of job due to RA, no. (%)35 (17)27 (18)8 (16)< 0.0001
Duration of RA, mean ± SD (range) years5.1 ± 7.8 (0–46)5.4 ± 8.1 (0–46)4.3 ± 7.1 (0–39)0.36
RA medications, %    

Of the 204 enrolled patients, 153 (75.0%) completed 6 months of treatment (continuers), while 51 (25.0%) discontinued therapy (discontinuers). Discontinuers had a higher proportion of women (P < 0.0001), fewer college graduates (P < 0.0001), and greater proportions of patients with part-time employment (P < 0.0001) and participation in service occupations (P < 0.0001) (Table 1). Among discontinuers, 9.8% (n = 5) discontinued therapy within 1 month of initiation, while 21.6% (n = 11), 17.6% (n = 9), and 47.1% (n = 24) discontinued by months 2, 3, and 6, respectively. The most common reasons for discontinuation were medical (e.g., lack of effectiveness; 77.5%) and financial (e.g., insurance company coverage; 22.5%).

Work impairment

For all patients at baseline, a mean of 3.8 hours per week was lost from work because of RA, with absenteeism and presenteeism scores of 9.9% and 39.7%, respectively, while the overall work impairment score was 43.2% (Table 2). The absenteeism score was equivalent to annual losses of ∼24.8 days, assuming an 8-hour day, 40-hour week, and 50 work weeks per year. Using standard assumptions ([25]), the 39.7% presenteeism score was equivalent to a productivity loss of 15.9 additional hours per week or 99.3 days of work per year. Therefore, patients had a total potential annual loss of 124.1 days through absenteeism and presenteeism as a result of RA at baseline, although only 20% of this time loss (24.8 days) was actually due to days missed from work; the remainder was due to patient estimates of their reduced productivity. Compared with continuers, discontinuers reported increases of 81.2% in time lost from work, 70.2% in absenteeism, and 12.9% in overall work impairment at baseline. However, presenteeism (38.9% for continuers versus 42.2% for discontinuers) and activity impairment (55.7% for continuers versus 57.6% for discontinuers) were similar for both groups at baseline. For continuers, etanercept led to significant improvements in time lost from work over 7 days (decrease of 1.7 hours) and decreases in absenteeism (4.1%), presenteeism (14.1%), overall work impairment (15.8%), and activity impairment (24.8%) over 6 months of therapy (P = 0.0001 for all parameters) (Table 2). In contrast, discontinuers demonstrated no significant changes in hours lost from work, absenteeism, or activity impairment, but they did show significant decreases in presenteeism (P = 0.0079) and overall work impairment (P = 0.004) over the 6-month observation period (Table 2).

Table 2. Impact of etanercept on hours missed from work and WPAI-RA parameters over 6 months*
ParameteraBaseline, mean ± SD (no.)6 months, mean ± SD (no.)Change from baselinebPc
Mean ± SD (no.)(95% CI)
  1. WPAI-RA = rheumatoid arthritis (RA)–specific Work Productivity and Activity Impairment Questionnaire; 95% CI = 95% confidence interval.
  2. aContinuers were patients who continued on etanercept over the 6-month period; discontinuers were patients who either switched or discontinued etanercept.
  3. bAnalysis on change of scores from baseline was based on patients with data at both baseline and 6 months.
  4. cP determined by Wilcoxon's signed rank test.
Time missed due to RA over last 7 days, hours     
All patients3.8 ± 8.0 (203)1.6 ± 6.2 (183)−1.5 ± 7.0 (183)−2.5, −0.40.0005
Continuers3.2 ± 7.5 (153)0.8 ± 3.7 (148)−1.7 ± 6.0 (148)−2.7, −0.80.0001
Discontinuers5.8 ± 9.3 (50)5.1 ± 11.5 (35)−0.3 ± 10.3 (35)−3.9, 3.20.5625
Overall work impairment, %     
All patients43.2 ± 26.4 (196)26.0 ± 23.5 (170)−15.2 ± 24.6 (168)−19.0, −11.5< 0.0001
Continuers41.9 ± 25.2 (147)25.2 ± 23.6 (141)−15.8 ± 25.1 (139)−20.0, −11.5< 0.0001
Discontinuers47.3 ± 29.6 (49)30.0 ± 23.0 (29)−12.6 ± 22.0 (29)−21.0, −4.30.0040
Absenteeism, %     
All patients9.9 ± 20.1 (199)4.4 ± 16.1 (174)−3.5 ± 17.0 (172)−6.1, −1.00.0009
Continuers8.4 ± 18.8 (149)2.3 ± 9.9 (142)−4.1 ± 14.2 (140)−6.5, −1.80.0001
Discontinuers14.3 ± 23.2 (50)13.8 ± 29.8 (32)−1.0 ± 25.9 (32)−10.3, −8.40.5152
Presenteeism, %     
All patients39.7 ± 24.5 (196)24.8 ± 22.5 (170)−13.5 ± 23.3 (168)−17.0, −9.9< 0.0001
Continuers38.9 ± 23.8 (147)24.3 ± 22.9 (141)−14.1 ± 24.1 (139)−18.1, −10.1< 0.0001
Discontinuers42.2 ± 26.6 (49)27.2 ± 20.5 (29)−10.3 ± 19.5 (29)−17.8, −2.90.0079
Activity impairment, %     
All patients56.2 ± 23.1 (203)34.4 ± 28.1 (191)−21.4 ± 26.7 (191)−25.2, −17.6< 0.0001
Continuers55.7 ± 22.8 (153)30.9 ± 26.6 (153)−24.8 ± 25.2 (153)−28.8, −20.8< 0.0001
Discontinuers57.6 ± 24.2 (50)48.4 ± 30.2 (38)−7.9 ± 28.9 (38)−17.4, 1.60.1463

The change in WPAI-RA parameters was rapid in continuers; absenteeism, presenteeism, overall work impairment, and activity impairment had all improved significantly within 1 month of etanercept initiation (P < 0.0001 for all, except for absenteeism [P = 0.01]) (Figure 1). Following this rapid improvement after 1 month of therapy, the continuers' scores for presenteeism and work and activity impairment showed small levels of continuing improvement up to 6 months from baseline, remaining relatively stable, while absenteeism continued to improve. In contrast, time course data for discontinuers showed a disjointed pattern of change over time, with no clear consistent evidence of a rapid and maintained impact on WPAI parameters 1 month after study initiation (data not shown). The significance of change in WPAI-RA scores from baseline in continuers was similar using nonparametric Wilcoxon's tests and mixed-model tests. WPAI-RA scores across all patients showed similar significant changes (ranging from P < 0.0001 to P = 0.001) over the 6-month followup period (Table 2). As with continuers, these changes were rapid, with significant improvement using both Wilcoxon's tests and mixed-model tests in all WPAI-RA parameters from baseline to 1 month after etanercept initiation (Figure 1).

Figure 1.

Mean rheumatoid arthritis–specific Work Productivity and Activity Impairment scores with 95% confidence interval (95% CI) for overall work impairment (A), absenteeism (B), presenteeism (C), and activity impairment (D) at baseline and months 1, 2, 3, and 6 for all patients and continuers. The mean scores were based on patients with data at each time point. P values were determined using Wilcoxon's signed rank probability. § = P < 0.0001; ‡ = P < 0.001; * = P < 0.05; † = P < 0.01; BL = baseline.

The linear regression analysis showed that part-time employment status was associated with significantly higher presenteeism (P = 0.02) and overall work impairment (P = 0.02) than full-time employment status at month 6 in all patients. Fair/poor self-reported health status at baseline resulted in higher levels of absenteeism (P = 0.02) and activity impairment (P = 0.01) at the end of the treatment period. Absenteeism was also significantly associated with race/ethnicity (P = 0.0007), with Asian or Hispanic patients showing greater absenteeism due to RA than other groups at month 6. Finally, outcomes of all 4 WPAI-RA domains at the end of the treatment period were significantly associated with the baseline percentage of work impairment (ranging from P < 0.0001 to P = 0.004).

Domestic productivity

In continuers, domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001) (Table 3). Satisfaction with domestic productivity for continuers also increased significantly from baseline to 6 months (score of 2.5 versus 3.3; P < 0.0001). Significant changes in domestic productivity and satisfaction with domestic productivity were also observed for all patients and discontinuers, although improvement in the latter population was smaller.

Table 3. Impact of etanercept on domestic productivity and satisfaction with domestic productivity*
ParameteraBaseline, mean ± SD (no.)6 months, mean ± SD (no.)Change from baselinebPc
Mean ± SD (no.)(95% CI)
  1. 95% CI = 95% confidence interval.
  2. aContinuers were patients who continued on etanercept over the 6-month period; discontinuers were patients who either switched or discontinued etanercept.
  3. bAnalysis on change of scores from baseline was based on patients with data at both baseline and 6 months.
  4. cP determined by Wilcoxon's signed rank test.
  5. dMeasured on a 1–5 Likert scale, where 1 = not at all satisfied and 5 = completely satisfied.
Domestic productivity, %d     
All patients39.6 ± 31.0 (202)65.4 ± 32.1 (186)24.9 ± 32.8 (186)20.1, 29.6< 0.0001
Continuers41.5 ± 31.4 (153)69.6 ± 29.9 (149)27.4 ± 32.8 (149)22.1, 32.7< 0.0001
Discontinuers33.7 ± 29.3 (50)48.4 ± 35.6 (37)14.6 ± 31.2 (37)4.2, 25.00.0153
Satisfaction with domestic productivity scored     
All patients2.4 ± 1.1 (203)3.3 ± 1.3 (191)0.8 ± 1.3 (191)0.6, 1.0< 0.0001
Continuers2.5 ± 1.1 (153)3.3 ± 1.3 (153)0.9 ± 1.3 (153)0.7, 1.1< 0.0001
Discontinuers2.3 ± 1.0 (50)2.9 ± 1.3 (38)0.6 ± 1.2 (38)0.2, 1.00.0079

Economic impact of etanercept therapy

Extrapolation of reductions in absenteeism with etanercept to 1 year showed a gain of 63.5 hours for the total population (Table 4); the reduced presenteeism with treatment over the same period was equivalent to an annual gain of 189.7 hours. As predicted by the greater improvements in all WPAI-RA parameters, continuers gained more hours through reduced absenteeism (71.1 versus 63.5 hours) and presenteeism (205.2 versus 189.7 hours) than all patients (Table 4). The total annual productivity gain for continuers due to etanercept therapy was estimated at 284.5 hours per patient for an average economic gain of $8,279 per person (74.2% due to projected increases in productivity). As a result, the annual cost of etanercept treatment was partially offset by the increased productivity, with the average net drug treatment cost being $11,910 (rather than $20,190). When continuers were categorized by income level, extensive variations in hours gained and net economic impact of therapy were observed. The total time gained varied from 181.8 hours for patients with salaries from $30,000 to <$60,000 to 450.4 hours for patients in the ≥$90,000 category. This variation in continuer productivity gains by income level resulted in variation in the overall net economic impact when the cost of etanercept was included. For patients earning ≥$90,000, productivity gains were equivalent to an annual dollar value of $22,533 (73.6% from presenteeism) and the net economic impact of etanercept was a gain of $2,343. Results were similar for all patients, but generally lower because of the inclusion of discontinuers, which lowered all productivity gains compared to continuers.

Table 4. Average annual gains in productivity in all patients and continuers after treatment with etanercept and estimated net economic impact
Productivity componentAll income levels (n = 203)Income level
<$30,000 (n = 44)$30,000 to <$60,000 (n = 87)$60,000 to <$90,000 (n = 46)≥$90,000 (n = 26)
  1. aAll income levels n = 179, <$30,000 n = 37, $30,000 to <$60,000 n = 76, $60,000 to <$90,000 n = 42, and ≥$90,000 n = 24.
  2. bTotal hours gained was based on patients with no missing values for both absenteeism and presenteeism and is not identical to the sum of means for each separate component.
  3. cNet economic gain is the annual dollar value of productivity gains − the annual cost of etanercept. The cost of etanercept was based on the 2009 wholesale acquisition costs of $194.13 per 25 mg or annual treatment costs of $20,189.52.
  4. dAll income levels n = 144, <$30,000 n = 32, $30,000 to <$60,000 n = 62, $60,000 to <$90,000 n = 31, and ≥$90,000 n = 19.
All patientsa     
Hours gained/patient     
Total hours gainedb275.3297.9215.8292.1390.8
Economic gain/patient     
Total economic gain$7,664.87$3,463.42$3,915.59$10,049.84$19,448.13
Net economic gainc−$12,524.65−$16,726.10−$16,273.93−$10,139.68−$741.39
Continuer patientsd     
Hours gained/patient     
Total hours gainedb284.5336.7181.8329.1450.4
Economic gain/patient     
Total economic gain$8,279.36$3,927.33$3,233.06$12,022.54$22,532.55
Net economic gainc−$11,910.16−$16,262.19−$16,956.46−$8,166.98$2,343.03


The burden of RA in this employed, real-world population of US patients at baseline was high in terms of absenteeism and presenteeism, despite most patients receiving standard nonbiologic therapy. Patients reported absenteeism and presenteeism scores of 9.9% and 39.7%, respectively, leading to a total potential annual loss of 124.1 days per year as a result of RA, which is consistent with the previously reported impact of early RA on productivity outcomes ([8, 9, 31]). For the patients who completed at least 6 months of treatment, etanercept had a rapid and significant impact on all productivity parameters, which was apparent within 1 month of therapy initiation. These rapid changes in productivity were likely a reflection of clinical improvement with etanercept, which can be apparent within 2 weeks of the start of therapy in patients who respond to etanercept ([32, 33]). On the basis of projections over 12 months for continuers, changes in absenteeism after initiation of etanercept therapy resulted in a gain of 71.1 working hours, and reductions in presenteeism were equivalent to a further gain of 205.2 hours.

The positive impact of etanercept on work disability in RA has been reported by others ([8, 11, 12, 34]); this study also showed that etanercept had a significant impact on both absenteeism and presenteeism in employed RA patients. In a study of patients with early active RA by Anis et al, treatment with etanercept plus methotrexate led to 31.3 fewer days lost in annual productivity compared with methotrexate monotherapy, which is similar to results for continuers from our study (284.5 hours or 35.6 days) ([8]). Presenteeism in the study by Anis et al was estimated by relating Health Assessment Questionnaire scores from treated patients to WPAI scores using a published mapping algorithm ([8, 35]). Similarly, in a retrospective, observational, cross-sectional survey of employed US patients with RA, Globe et al found that initiation of etanercept led to a decrease in missed work days per month (from 1.8–0.1 days; P < 0.001) over a mean treatment period of 16.5 months, as well as decreases in patient-reported presenteeism ([12]). Although the studies by Anis et al and Globe et al included different study designs and used different measures to evaluate work productivity, these findings are consistent with the current study, indicating that etanercept has a significant impact on both absenteeism and presenteeism in employed patients with RA.

For continuers, the beneficial impact of etanercept led to a substantial economic impact through increases in productivity and generated savings through reductions in absenteeism and presenteeism. The total annual savings partially or completely offset the treatment cost of etanercept, which was more apparent with higher salaries. Similar to our findings, Globe et al reported in an analysis from 2006–2007 using the Work Loss and Productivity Survey that annual savings through reduced absenteeism ($3,889) and increased productivity ($19,065) with etanercept offset the cost of treatment ($16,389 annually), generating a savings of up to $6,566 per treated employed patient (ranging from a deficit of $3,803 in patients earning <$40,000 per year to a savings of $21,904 in those earning ≥$80,000 per year) ([12]). Anis et al also noted economic benefits from reductions in absenteeism with etanercept plus methotrexate combination therapy in patients with RA in the UK ([8]). Although the study designs and populations differed, collectively these results confirm that the cost of etanercept treatment can be offset to varying degrees as a result of improvements in work productivity.

The benefits of etanercept also extended beyond decreases in absenteeism, presenteeism, overall work impairment, and activity impairment, with significant gains in domestic productivity and satisfaction with domestic productivity. This indicates that the impact of etanercept is apparent beyond the work place and that the beneficial clinical impact of this drug also has a positive effect on functioning in or around the home.

Zhang et al reported that the WPAI provides higher estimates of presenteeism in employed patients with arthritis than other similar instruments ([25]), suggesting that presenteeism may have been overestimated in our study. However, the purpose of the study was to assess changes in presenteeism and absenteeism in working patients with RA with etanercept therapy, and the WPAI was selected because it is validated for RA ([19]) and is easily completed by patients ([36]). It is also possible that presenteeism may have been underreported in our study because patients with RA may be reluctant to report these work issues. Nevertheless, confirmation of the absolute gains in productivity with etanercept and the monetary gains awaits further investigation.

An additional limitation of this study is that data on clinical outcomes were not collected; therefore, productivity gains could not be correlated with improvement in RA clinical outcomes following initiation of etanercept therapy. However, the WPAI-RA correlates strongly with measures of RA health status, including improved patient function, and data suggest that WPAI-RA improvements reflect better functioning and less pain and fatigue as a consequence of therapy ([19]).

Productivity gains with etanercept were estimated based on the change in WPAI-RA measures from baseline, with the assumption that in untreated patients, productivity at 6 months was identical to that at baseline. However, RA is a progressive disease and productivity loss may have continued to increase over 6 months in untreated patients, resulting in an underestimation of productivity gains with 6 months of etanercept therapy. The cost consequences of increased productivity were based on a projection of absenteeism and presenteeism gains over 12 months. This assumed that productivity gains were unchanged over 12 months, which may not have been the case for all workers. In addition, the net impact of productivity gains for all patients was based on intent-to-treat principles (patients who received etanercept for 6 months), even though this population included discontinuers who stopped therapy over the treatment period. Therefore, net gain estimates for all patients were likely underestimated because the annual per-patient cost of etanercept would actually be <$20,190 if corrected for discontinuers. It was not possible to track etanercept dosing for every discontinuer, partially because some were lost to followup. Similarly, the costing analysis assumed that all continuers received etanercept at 25 mg twice weekly for 12 months; in fact, there may have been variation in this dosing pattern, which would impact treatment costs. Although not assessed here, etanercept may also have led to reductions in direct medical costs as a result of improvement in clinical outcomes and a reduced need for health care services such as hospitalization and concomitant medication use ([37]). Despite these limitations, the current study provides a measure of the potential annual financial impact of etanercept on productivity outcomes in working patients with RA.

In conclusion, US-based employed patients with moderate to severe RA in this study showed rapid and significant improvements in productivity at work and reductions in the number of work days lost due to RA after initiation of etanercept. There were also significant improvements in the ability to perform daily activities and domestic productivity. From an employer perspective, this study demonstrates that, depending on income levels, the cost of initiating etanercept treatment in workers with RA is partially or completely offset by the resulting increased productivity.


All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Ms Hone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Cheng, Watson, Bitman, Xing-Yue Huang, Gandra.

Acquisition of data. Hone, Cheng.

Analysis and interpretation of data. Hone, Cheng, Watson, Baisong Huang, Bitman, Xing-Yue Huang, Gandra.


The authors affiliated with Amgen participated in the study design and interpretation of the data, writing of the manuscript, and decision to submit the manuscript for publication. Amgen provided input during the manuscript development process, but any resulting revisions to the content of the manuscript were dependent on author approvals. Wyeth and Pfizer had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was contingent upon approval by Immunex Corporation, Amgen, Wyeth, and Pfizer.


Ms Hone is an employee of McKesson Specialty (Canada). Mr. Baisong Huang is a former employee of McKesson Specialty (Canada). Ms. Cheng is a former employee of McKesson Specialty (US). Ms Watson is currently employed by Biogen Idec, but was not at the time of the study. Dr. Xing-Yue Huang is currently employed by Health Economics and Outcomes Research, but was not at the time of the study.


The authors would like to thank John McCormick, PhD, McKesson Specialty (Canada), for his assistance in the preparation of the manuscript.