Background/Purpose:

Fluctuations in disease activity due to short-term situational effects and measurement errors are important considerations for evaluation of individual clinically meaningful therapeutic response in daily practice in patients with rheumatoid arthritis (RA). 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-ESR)¹. In this analysis, DAS28_dcrit response was evaluated post-hoc from a RCT (ADACTA²) comparing Tocilizumab (TCZ) to Adalimumab (ADA) treatment.

Methods:

Patient population was derived from ADACTA² with active RA treated with monotherapy of TCZ (8mg/kg) and ADA (40 mg e.o.w.).325 patients were analyzed. DAS28_dcrit response of 1.8 was used as cut off for an individual important improvement of DAS28 derived from the established statistical approach on validation of DAS28_dcrit response¹. The cohort was used to calculate the proportion achieving DAS28_dcrit response at every study visit (BL up to week 24). DAS28 dcrit response was compared to standard disease activity measurements. Achievement of DAS28_dcrit response at multiple visits in individual patients (not consecutive) was evaluated.

Results:

Patient population of both treatment arms was comparable in disease activity at baseline, balance of gender and pretreatment. In the TCZ group, 53.8% of the patients achieved DAS28_dcrit response at week 4, 75.2% at week 8, 82.7% at week 12, 84.5% at week 16, 89.5% at week 20 and 90.1% at week 24. In the ADA group, 36.6% achieved DAS28_dcrit response at week 4, and 44.8% at week 8, 48.6% at week 12, 51.4% at week 16, 63.0% at week 20 and 59.1% at week 24 (Table 1). In the TCZ group, 88.3% of patients achieved DAS28_dcrit response at least at 3 visits, 77.9% at least at 4, 65.5% at least at 5 and 37.2% at least at 6 visits; for the ADA group, 67.8% at least at 3, 53.0% at least at 4, 40.9% at least at 5 and 22.6% at least at 6 visits.

Conclusion:

The established critical differences for DAS28 (DAS28_dcrit) of 1.8 was confirmed in an independent cohort of ADA-treated patients¹. In the RCT ADACTA², for the cut-off of 1.8, high percentages of patients achieved this level of response even early after initiation of TCZ-treatment (week 4 and 8) compared to ADA treatment. Stability of TCZ treatment effect was shown by approx. 78% of the patients (compared to 53.0% for ADA) with at least 4 visits out of 6 with DAS28_dcrit response.

References:

¹Behrens F, Tony HP, Alten R, Kleinert S, Scharbatke EC, Köhm M, Gnann H, Tams J, Greger G, Burkhardt H. Development and validation of a new disease activity score in 28 joints-based treatment response criterion for rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013 Oct;65(10):1608-16. doi: 10.1002/acr.22037.

²Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, Klearman M, Musselman D, Agarwal S, Green J, Kavanaugh A; ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013 May 4;381(9877):1541-50. doi: 10.1016/S0140-6736(13)60250-0. Epub 2013 Mar 18. Erratum in: Lancet.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-analysis-of-achievement-of-individual-important-response-measured-by-das28dcrit-in-a-randomized-head-to-head-trial-of-tocilizumab-vs-adalimumab-in-active-rheumatoid-arthritis/