Backround: A New Definition of Treatment Response in Rheumatoid Arthritis: Identification of the Critical Difference in Disease Activity Sunday 363 Frank Behrens 1 , Michaela Koehm 1 , Eva C. Scharbatke 2 , Stefan Kleinert 2 , Geerd Weyer 3 , Rieke Alten 4 , Hans Peter Tony 2 and Harald Burkhardt 1 1 CIRI/ Rheumatology, J.W. Goethe-University, Frankfurt/Main, 2 Rheumatology, University of Würzburg, 3 Biostatistics, ICRC, Berlin, 4 Rheumatology Schlossparkklinik, Berlin, Germany Situational effects and measurement errors inducing fluctuations in disease activity measurements complicate the evaluation of a clinically meaningful therapeutic response in rheumatoid arthritis (RA). To itemize this complexity, a statistical approach was used to determine a critical difference (dcrit) defining valid criterion for clinical response as assessed by the Disease Activity Score-28 joints (DAS28): DAS28dcrit. Background: Conclusion: Based on our data, a DAS28dcrit value of 1.8 (DAS28 improvement of 1.8 points) signifies an individual therapeutic response that exceeds the threshold of random fluctuation. The dcrit value determined by statistical analysis of expected variation in DAS28 scores higher than the DAS28 change required to achieve a good EULAR response (1.2 points) and is independent of baseline activity, which may make it more convenient for clinical use. Further studies in larger populations will be required to confirm the utility of the dcrit value in determining therapeutic response. However, our data suggest that a dcrit value of 1.8 has the potential to guide treatment decisions in daily clinical practice and to facilitate research on treatment responders. The overall dcrit value in the 728 patient populations was detected at 1.75. Values for DAS28dcrit were comparable in all evaluated subgroups, regardless of treatment centre, class of therapy (DMARDs or biologics including TNF-inhibitors and Rituximab), or baseline disease activity (Table). Results: all patients DAS28 M12 Class of therapy Age Gender ≤ 3.2 > 3.2 DMARDs Biologics ≤ 60 years > 60 years male female n 728 393 335 57 671 460 268 167 561 dcrit 1.75 1.57 1.79 1.90 1.73 1.74 1.77 1.65 1.78 Table 2: DAS28DCRIT - 2 - 1,5 - 1 - 0,5 0 EULAR Response DAS<3.2 DAS>3.2 DCRIT Area of normal fluctuation (stable medication , stable disease activity) good moderate non DAS28 Figure 2: EULAR vs. DAS28DCRIT Table 1: Demographic Data Parameter Age, yrs (SD) 54.8 (12.4) Females, % 77.0 BMI, kg/m 2 (SD) 25.9 (4.6) Disease duration, yrs (SD) 11.5 (8.9) Tender joint count (SD) 12.6 (7.2) Swollen joint count (SD) 9.8 (6.2) CRP, mg/L (SD) 32.8 (63.2) ESR, mm/h (SD) 33.0 (21.8) Rheumatoid factor, % 77.4 Erosive changes, % 76.7 Rheumatoid nodules, % 24.3 Joint replacement surgery, % 15.3 Patient global assessment-VAS (SD) 6.5 (1.9) DAS28 (SD) 5.9 (1.1) FFbH, % remaining functional capacity (SD) 60.2 (22.8) Concomitant therapy Any conventional DMARD, % 77.4 MTX, % 58.1 Leflunomide, % 19.4 Glucocorticoids, % 85.1 The population comprised a total number of 728 RA patients with stable response to DMARD, steroid or biological therapy (including TNF-inhibitors and Rituximab) derived from three different clinics in Germany (University Würzburg, University Frankfurt, Berlin) and from a prospective observational study with Adalimumab. Patients were included with stable therapy and disease course from months 12 to 24 after therapy initiation. Methods: Methods: To evaluate changes in DAS28 score, DAS28 scores at 12, 18 and 24 months were subjected to an ANOVA model to determine the error of measurement which was used to establish a 95% one sided confidence interval (95% CI) for decrease occurring by chance within the range of normal fluctuations. The limit of the confidence region defined the critical difference (dcrit) in disease activity for a reliable change in a single patient. Figure 1: Interindividual trends The authors would like to thank Abbott and Wyeth/Pfizer for providing anonymized data sets from prospective observational studies in Germany. Acknowledgements:
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Backround:
A New Definition of Treatment Response in Rheumatoid Arthritis: Identification of the Critical Difference in Disease Activity Sunday 363
Frank Behrens1, Michaela Koehm1, Eva C. Scharbatke2, Stefan Kleinert2, Geerd Weyer3, Rieke Alten4, Hans Peter Tony2 and Harald Burkhardt1 1CIRI/ Rheumatology, J.W. Goethe-University, Frankfurt/Main, 2Rheumatology, University of Würzburg, 3Biostatistics, ICRC, Berlin, 4Rheumatology Schlossparkklinik, Berlin, Germany
Situational effects and measurement errors inducing fluctuations in disease activity measurements complicate the evaluation of a clinically meaningful therapeutic response in rheumatoid arthritis (RA). To itemize this complexity, a statistical approach was used to determine a critical difference (dcrit) defining valid criterion for clinical response as assessed by the Disease Activity Score-28 joints (DAS28): DAS28dcrit.
Background:
Conclusion: Based on our data, a DAS28dcrit value of 1.8 (DAS28 improvement of 1.8 points) signifies an individual therapeutic response that exceeds the threshold of random fluctuation. The dcrit value determined by statistical analysis of expected variation in DAS28 scores higher than the DAS28 change required to achieve a good EULAR response (1.2 points) and is independent of baseline activity, which may make it more convenient for clinical use. Further studies in larger populations will be required to confirm the utility of the dcrit value in determining therapeutic response. However, our data suggest that a dcrit value of 1.8 has the potential to guide treatment decisions in daily clinical practice and to facilitate research on treatment responders.
The overall dcrit value in the 728 patient populations was detected at 1.75. Values for DAS28dcrit were comparable in all evaluated subgroups, regardless of treatment centre, class of therapy (DMARDs or biologics including TNF-inhibitors and Rituximab), or baseline disease activity (Table).
Results:
all
patients
DAS28 M12
Class of therapy Age Gender
≤ 3.2
> 3.2
DMARDs Biologics ≤ 60 years
> 60 years
male female
n
728
393
335
57
671
460
268
167
561
dcrit
1.75
1.57
1.79
1.90
1.73
1.74
1.77
1.65
1.78
Table 2: DAS28DCRIT
- 2
- 1,5
- 1
- 0,5
0
EULAR Response
DAS<3.2 DAS>3.2 DCRIT
Are
a of
nor
mal
fluc
tuat
ion
(sta
ble
med
icat
ion
, sta
ble
dise
ase
activ
ity)
good moderate non
DA
S28
Figure 2: EULAR vs. DAS28DCRIT
Table 1: Demographic Data Parameter
Age, yrs (SD) 54.8 (12.4)
Females, % 77.0
BMI, kg/m2 (SD) 25.9 (4.6)
Disease duration, yrs (SD) 11.5 (8.9)
Tender joint count (SD) 12.6 (7.2)
Swollen joint count (SD) 9.8 (6.2)
CRP, mg/L (SD) 32.8 (63.2)
ESR, mm/h (SD) 33.0 (21.8)
Rheumatoid factor, % 77.4
Erosive changes, % 76.7
Rheumatoid nodules, % 24.3
Joint replacement surgery, % 15.3
Patient global assessment-VAS (SD) 6.5 (1.9)
DAS28 (SD) 5.9 (1.1)
FFbH, % remaining functional capacity (SD)
60.2 (22.8)
Concomitant therapy
Any conventional DMARD, % 77.4
MTX, % 58.1
Leflunomide, % 19.4
Glucocorticoids, % 85.1 !
The population comprised a total number of 728 RA patients with stable response to DMARD, steroid or biological therapy (including TNF-inhibitors and Rituximab) derived from three different clinics in Germany (University Würzburg, University Frankfurt, Berlin) and from a prospective observational study with Adalimumab. Patients were included with stable therapy and disease course from months 12 to 24 after therapy initiation.
Methods:
Methods: To evaluate changes in DAS28 score, DAS28 scores at 12, 18 and 24 months were subjected to an ANOVA model to determine the error of measurement which was used to establish a 95% one sided confidence interval (95% CI) for decrease occurring by chance within the range of normal fluctuations. The limit of the confidence region defined the critical difference (dcrit) in disease activity for a reliable change in a single patient.
Figure 1: Interindividual trends
The authors would like to thank Abbott and Wyeth/Pfizer for providing anonymized data sets from prospective observational studies in Germany.
Acknowledgements:
Related Documents
