Ina H. Kuper

Productivity loss due to absenteeism and presenteeism by different instruments in patients with RA and subjects without RA

OBJECTIVES To explore the impact of at-work productivity loss on the total productivity cost by different instruments in patients recently diagnosed with RA and controls without RA. METHODS Cross-sectional data were collected from outpatients with RA between December 2007 and February 2008. The control group was formed by subjects without RA matched on age and gender. Absenteeism and presenteeism were estimated by the Quantity and Quality (QQ) Questionnaire, Work Productivity and Activity Impairment Questionnaire General Health V2.0 (WPAI-GH) and Health and Labor Questionnaire (HLQ) questionnaires. Differences between groups were tested by Mann-Whitney U-test. Costs were valued by the human capital approach. RESULTS Data were available from 62 patients with a paid job and 61 controls. QQ- and WPAI-GH scores of presenteeism were moderately correlated (r = 0.61) while the HLQ presenteeism score correlated poorly with the other instruments (r = 0.34). The contribution of presenteeism on total productivity costs was estimated at ∼70% in the RA group. The mean costs per person per week due to presenteeism varied between €79 and €318 per week in the RA group, dependent on the instrument used. The costs due to presenteeism were about two to four times higher in the RA group compared with the control group. CONCLUSION This study indicates that the impact of presenteeism on the total productivity costs in patients with RA is high. However, work productivity in individuals without RA was not optimal either, which implies a risk of overestimation of cost when a normal score is not taken into account. Finally, different presenteeism instruments lead to different results.

The Reason for Discontinuation of the First Tumor Necrosis Factor (TNF) Blocking Agent Does Not Influence the Effect of a Second TNF Blocking Agent in Patients with Rheumatoid Arthritis

Objective. To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. Methods. Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking agents. Patients were divided into 3 groups based on reason for discontinuation of the first: nonresponse, loss of response, or adverse events. The primary outcome was the change from baseline of the disease activity (by DAS28) at 6 months, corrected for the baseline DAS28 score. Secondary outcomes were the change from baseline at 3 months, EULAR response rates, and the percentages of patients who reached a DAS28 score ≤ 3.2 at 3 and at 6 months. Results. In total, 49 patients who failed due to nonresponse, 75 due to loss of response, and 73 due to adverse events were included. At 6 months, the change of DAS28 score from baseline did not differ significantly between the groups (−0.6 to −1.3; p ≥ 0.173) and similar good and moderate response rates were found (12% to 18%, p ≥ 0.523, and 34% to 55%, p ≥ 0.078, respectively). The secondary outcomes were also comparable between the 3 groups. Conclusion. The results of our observational study suggest that a second TNF blocking agent may be effective after failure of the first, regardless of the reason for discontinuation of the first TNF blocking agent.

Effectiveness of a third tumor necrosis factor-α-blocking agent compared with rituximab after failure of 2 TNF-blocking agents in rheumatoid arthritis.

Objective. To compare the effectiveness of a third tumor necrosis factor-α (TNF-α)-blocking agent with rituximab after failure of 2 TNF-blocking agents in patients with rheumatoid arthritis (RA) in daily clinical practice. Methods. Patients receiving a third TNF-blocking agent or rituximab after failure of 2 TNF-blocking agents were selected from a Dutch biologic registry. The primary outcome was the results from the Disease Activity Score of 28 joints (DAS28) over the first 12 months after start of the third biologic using mixed-model analyses. Secondary outcomes included the course of the Health Assessment Questionnaire (HAQ) and the separate components of the DAS28 over the first 12 months and the change from baseline in DAS28 and HAQ at 3 and 6 months. Results. The overall course of the DAS28 over the first 12 months was significantly better for rituximab (p = 0.0044), as also observed for the HAQ, although the latter results were not statistically significant (p = 0.0537). The erythrocyte sedimentation rates, C-reactive protein, and swollen joint counts showed a better course for rituximab (p = 0.0008, p = 0.0287, p = 0.0547, respectively), but not the tender joint counts or visual analog scale for general health. DAS28 decreased significantly in both groups at 3 and 6 months (p ≤ 0.024), but the change in HAQ was significant for rituximab only at 3 months (p = 0.009). Conclusion. During the first 12 months of therapy, a larger improvement in disease activity and a trend toward a larger decrease in functional disability was observed in patients receiving rituximab. Switching to a biologic with another mechanism of action might be more effective after failure of 2 TNF-blocking agents in RA.

Validating the 28-Tender Joint Count Using Item Response Theory

Objective. To examine the construct validity of the 28-tender joint count (TJC-28) using item response theory (IRT)-based methods. Methods. A total of 457 patients with early stage rheumatoid arthritis (RA) were included. Internal construct validity of the TJC-28 was evaluated by determining whether the TJC-28 fit a 2-measure logistic IRT model. As well, we tested whether the discrimination and difficulty parameters of the joints properly reflected the known left-right symmetry of joint involvement. External validity was evaluated by correlations with other established measures of disease activity, including pain, disability, general health, erythrocyte sedimentation rate (ESR), and the 28-swollen joint count. Results. The TJC-28 showed a good fit with the 2-parameter logistic model, with no relevant differential item functioning across sex, age, and time and with excellent reliability. The 28 joints covered a reasonable range of disease activity, even though they were mainly targeted at patients with moderate or high disease activity levels. The joint parameters reflected the left-right symmetry of joint involvement for all pairs of joints except one. All disease activity measures, except ESR, were significantly correlated with the TJC-28. Most correlations were of the expected magnitude. Conclusion. The TJC-28 showed good internal and acceptable external construct validity for patients with early-stage RA. The IRT analyses did point to some potential limitations of the instrument, a major problem being its limited measurement range. Future research should examine whether instrument modifications might lead to a more robust assessment of disease activity in patients with RA.

Contribution of assessing forefoot joints in early rheumatoid arthritis patients: Insights from item response theory.

To evaluate the contribution of assessing forefoot joints to the measurement range and measurement precision of joint counts in early rheumatoid arthritis (RA) using item response theory.

Validation of automatic joint space width measurements in hand radiographs in rheumatoid arthritis

Abstract. Computerized methods promise quick, objective, and sensitive tools to quantify progression of radiological damage in rheumatoid arthritis (RA). Measurement of joint space width (JSW) in finger and wrist joints with these systems performed comparable to the Sharp–van der Heijde score (SHS). A next step toward clinical use, validation of precision and accuracy in hand joints with minimal damage, is described with a close scrutiny of sources of error. A recently developed system to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was validated in consecutive hand images of RA patients. To assess the impact of image acquisition, measurements on radiographs from a multicenter trial and from a recent prospective cohort in a single hospital were compared. Precision of the system was tested by comparing the joint space in mm in pairs of subsequent images with a short interval without progression of SHS. In case of incorrect measurements, the source of error was analyzed with a review by human experts. Accuracy was assessed by comparison with reported measurements with other systems. In the two series of radiographs, the system could automatically locate and measure 1003/1088 (92.2%) and 1143/1200 (95.3%) individual joints, respectively. In joints with a normal SHS, the average (SD) size of MCP joints was 1.7±0.2 and 1.6±0.3  mm in the two series of radiographs, and of PIP joints 1.0±0.2 and 0.9±0.2  mm. The difference in JSW between two serial radiographs with an interval of 6 to 12 months and unchanged SHS was 0.0±0.1  mm, indicating very good precision. Errors occurred more often in radiographs from the multicenter cohort than in a more recent series from a single hospital. Detailed analysis of the 55/1125 (4.9%) measurements that had a discrepant paired measurement revealed that variation in the process of image acquisition (exposure in 15% and repositioning in 57%) was a more frequent source of error than incorrect delineation by the software (25%). Various steps in the validation of an automated measurement system for JSW of MCP and PIP joints are described. The use of serial radiographs from different sources, with a short interval and limited damage, is helpful to detect sources of error. Image acquisition, in particular repositioning, is a dominant source of error.

Cost-Effectiveness and Cost-Utility Analysis of Treat-to-Target Versus Usual Care in Early Rheumatoid Arthritis: Results of the DREAM Registry

Background Treat-to-target (T2T) has proven to be more effective in achieving remission in early rheumatoid arthritis (RA) patients than usual care [1]. However, T2T has not been fully implemented in daily clinical practice yet. Moreover, it is unknown whether T2T is cost-effective. Objectives To analyse the cost-effectiveness and cost-utility of a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) <2.6) compared to usual care in early RA over the first two years of the disease. Methods Two early RA inception cohorts including patients who fulfilled the ACR 1987 criteria were compared. The T2T group (n=261) consisted of patients from the DREAM remission induction cohort and was treated according to a protocolized treatment strategy aiming at DAS28 remission. The usual care group (n=213) consisted of patients from the Nijmegen early RA inception cohort and was treated without DAS28-guided, protocolized treatment decisions. For both groups, direct medical costs were collected and compared with gain in effectiveness (DAS28 remission) and quality adjusted life years (QALYs) (EQ-5D utility estimated from the HAQ) over two years of follow-up. Results T2T produced a higher remission percentage (64.4% vs. 34.7%) and a larger gain in QALYs (median (IQR) 1.45 (1.24-1.55) vs. 1.39 (1.18-1.53), p=0.037) than usual care. The total mean (SD) costs per patient were €4.807 (7.434) in the T2T group and €3.806 (5.761) in the usual care group. The incremental cost-effectiveness ratio was €3.340 per patient in remission. The incremental cost-utility ratio was €18.259 per QALY. The figure presents the cost planes which show the relation between A) the differences in effectiveness and costs and B) the differences in utility and costs of T2T versus usual care. Anti-TNF therapy was given to more T2T patients (21.5% vs. 15.0%) and was prescribed earlier in the disease process, compared to usual care. Conclusions This quasi-experiment showed that over the first two years of treatment, T2T is associated with higher costs but also with substantial higher effectiveness. We conclude that T2T is cost-effective in daily clinical practice. References [1] Schipper et al, Ann Rheum Dis. 2011 (In press). Disclosure of Interest None Declared