Background/Purpose: The ACR Hybrid, officially recommended by the ACR as a revision to the ACR20/50/70 response criteria, combines the ACR20/50/70 scores with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. Despite the demonstrated higher sensitivity to patient-reported improvement than the ACR20 criterion [1], its application is still limited in clinical trials [2], possibly because the scientific community is not yet familiar with its use. Data from an ongoing drug trial in DMARD-naïve patients with early rheumatoid arthritis (RA) were used to compare the ACR Hybrid scores versus the traditional efficacy measures (ACR20/50/70) and DAS28.

Methods: To assess the validity of the ACR Hybrid measure, we used blinded data from the ongoing trial with the EP4 receptor antagonist CR6086 in early rheumatoid arthritis, DMARD-naïve patients (the CREATIVE study). This is a randomized, placebo-controlled, double-blind, dose response, Phase IIb, multicentre trial of CR6086 administered for 12 weeks in combination with methotrexate (NCT03163966). The study consists of a baseline evaluation and 4 post-baseline visits at the following time-points: weeks 3, 6, 9 and 12. The ACR Hybrid score was obtained calculating the mean percent change from baseline across the 7 ACR core set measures for each patient/visit and determining whether patients achieved ACR20, 50, or 70 responses at that visit. The ACR Hybrid scores were compared with ACR20/50/70 outcomes and DAS28 calculated at each post-baseline visit. Missing data were not imputed. Results are presented as number of visits, regardless of patients and time-points.

Results: A total of 146 patients newly diagnosed with RA by the 2010 ACR/EULAR classification criteria had been randomized in EU/non-EU countries at the time of the data cut-off (May 2018). Overall, 376 post-baseline visits were available for the analyses. ACR20 response was achieved in 157/376 (42%) visits, while mean percent changes in ACR core measures ≥20%, and therefore positive ACR Hybrid scores, were observed in 250 visits (i.e. 66% of total) (Table). Similarly, ACR50 response was achieved in 66/376 (18%) visits, while mean improvements in ACR core measures ≥50% were observed in 87 visits (i.e. 23% of total). ACR Hybrid scores and percent change from baseline in DAS28 were highly correlated (Spearman’s correlation -0.85).

Conclusion: Analysis of blinded data from an ongoing Phase IIb drug trial in early RA, DMARD-naïve patients encourages the use of the ACR Hybrid score and supports its role as a valuable endpoint in clinical trials. By increasing the sensitivity of the analysis, this new measure of RA response might facilitate the demonstration of differences between treatments.

[1] Ward MM et al. Arthritis Rheum. 2014; 66(9): 2339–2343.

[2] van Vollenhoven RF et al. Arthritis Care Res (Hoboken). 2011; 63:128–134.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/acr-hybrid-analysis-blinded-data-from-the-ongoing-phase-iib-trial-with-the-ep4-receptor-antagonist-cr6086-in-dmard-naive-patients-with-early-rheumatoid-arthritis/