Artikel
Measurement of individual critical differences in activity of Rheumatoid Arthritis: Confirmation and usage of DAS28-dcrit in Tocilizumab-treated patients with RA
Suche in Medline nach
Autoren
-
Frank Behrens
- CIRI am Klinikum der Johann Wolfgang Goethe-Universität, Rheumatologie, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt/Main
-
Michaela Köhm
- CIRI am Klinikum der Johann Wolfgang Goethe-Universität, Rheumatologie, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt/Main
-
Christof Specker
- Universitätsklinikum Essen, St. Josef Krankenhaus, Klinik für Rheumatologie und klinische Immunologie, Essen
-
Gerhard Fliedner
- Rheumapraxis, Osnabrück
-
Michael W. Hofmann
- Chugai Pharma Marketing Ltd., Frankfurt/Main
-
Rasmus Lüthje
- Chugai Pharma Marketing Ltd., Frankfurt/Main
-
Harald Louis Burkhardt
- Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik II, Rheumatologie, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Frankfurt/Main
| Veröffentlicht: | 12. September 2014 |
|---|
Gliederung
Text
Background: Normal fluctuations in disease-activity measurements are issues for evaluation of a therapeutic-response in daily practice in rheumatoid arthritis (RA) patients. To address this aspect we established a statistical approach to determine a critical difference (dcrit) that defines valid criterion for response as assessed by the Disease Activity Score-28 joints (DAS28) earlier. With this study the dcrit-criterion was implemented in a Tocilizumab (TCZ)-treated cohort to evaluate its cut-off and onset of response in an independent population.
Methods: The patient population was derived from the interim analysis of the prospective non-interventional study ICHIBAN in RA-patients TCZ-treated. 159 (of in total 305) patients fulfilled criteria for stable disease-course over 12 months to calculate dcrit by individual statistical approach according to the previous established concept. The criteria included individual stable TCZ-, DMARD-, Steroid- and NSAID-treatment and stable mean DAS28 of the whole cohort. To evaluate individual changes in DAS28-scores, we subjected DAS28 scores at 12, 18, and 24 months to an ANOVA model to establish a 95% one sided confidence interval (95% CI) for normal fluctuations. The total cohort was used to define onset of response by fulfilling DAS28-dcrit criteria.
Results: The mean baseline DAS28 from the stable cohort (n=159) was 5.46 and decreased to month 12 to 2.6. For the next year of treatment the mean DAS28 did not show significant differences (month 15 2.6, month 18 2.49, month 21 2.47 and month 24 2.51).
The calculation of the DAS28-dcrit cut-off in TCZ-monotherapy results in 1.81, for the population including combinational-therapy 1.9.
40.7% of the patients achieve DAS28-dcrit after 4 weeks of treatment with an increase of the responders up to 61.8% at week 12 and 69.6% at week 24. After 2-years of treatment 75.6% of the patients reach a stable DAS28-dcrit response.
Conclusion: The established DAS28-dcrit value of 1.8 (DAS28 improvement of 1.8 points) was confirmed in an independent cohort with TCZ-treated patients. A slightly higher critical difference was seen in patients treated with combinational-therapy possibly due to small numbers for analysis. Already after 4 weeks of treatment more than 40% of the patients achieved a DAS28-dcrit response.
