ASSOCIATION OF ACR CLINICAL RESPONSES WITH CDAI (CLINICAL DISEASE ACTIVITY INDEX) AND RAPID3 (ROUTINE ASSESSMENT OF PATIENT INDEX DATA 3) INDICES OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH CERTOLIZUMAB PEGOL PLUS METHOTREXATE

Background: CDAI (clinical disease activity index) and RAPID3 (routine assessment of patient index data 3) cut points defining responses that best match ACR20/50/70 response in rheumatoid arthritis (RA) patients (pts), are unknown. Objectives: To evaluate cut points in a study population treated with certolizumab pegol (CZP) plus methotrexate (MTX). Methods: ACR responders through Week (Wk) 12 from 393 CZP treated pts (400 mg at Wks 0, 2 and 4 then 200 mg every 2 Wks) plus MTX in RAPID 1 (NCT00152386) were categorized by proposed response (R) cut points in CDAI (change from baseline [CFB] ≥6.7, ≥10.0, ≥13.9) and RAPID3 (CFB ≥1.8, ≥3.6). ACR20/50/70 responses were compared with proposed categorizations using cross-tabulations, AUC under the ROC curve (AUC-ROC), % correctly classified (%CC) pts and kappa statistics. CART (classification and regression trees) modeling identified CDAI and RAPID3 cut points defining responses most closely associated with ACR20/50/70 responses. Results: Sensitivities were very high; at Wk 12, 93–100% ACR20/50/70 responders achieved CFB in CDAI (≥6.7,≥10.0,≥13.9). Positive predictive value [PPV] was lower indicating CDAI-R is not as strongly associated with ACR-R as ACR-R is with CDAI-R; lower specificities indicate that ACR nonresponse (NR) does not correspond well to CDAI-NR (particularly for ACR50/70). However, CDAI-NR predicts well ACR-NR (very high negative predictive value [NPV]) (Table). CFB in CDAI≥13.9 was most closely associated with ACR20-R (κ=0.57). Association between proposed CDAI categorizations and ACR50/70 was weak (κ=0.05–0.29). A similar trend was observed for RAPID3. CART modeling identified CFB in CDAI ≥13.80/≥20.15/≥20.15 and CFB in RAPID3 ≥5.46/≥7.28/≥5.53 as categorizations most closely associated with ACR20/50/70 responses. Table 1. Association between ACR20/50/70 response at week 12 and CDAI change from baseline (CFB) CDAI CFBCDAI Response (%)ACR Response (%)NPV - % Pts among those who do not achieve CDAI response who do not achieve an ACR response at Wk 12PPV - % Pts among those with CDAI response who also achieve an ACR response at Wk 12Sensitivity - % Pts among ACR responders at Wk 12 who also achieved CDAI responseSpecificity - % Pts among ACR non responders at Wk 12 who do not achieve CDAI responseAUC-ROC% CCKappa ACR20≥6.786.663.898.173.399.636.20.6876.60.41 ≥10.082.563.892.675.798.044.70.7178.70.48 ≥13.973.863.883.380.593.160.30.7781.20.57 ACR50≥6.786.632.910038.010019.90.6046.30.14 ≥10.082.532.910039.910026.10.6350.40.19 ≥13.973.832.999.044.399.238.70.6958.60.29 ACR70≥6.786.615.210017.510015.80.5828.50.05 ≥10.082.515.210018.410020.60.6032.60.07 ≥13.973.815.210020.610030.90.6541.40.12 Conclusions: CDAI and RAPID3 CFB thresholds were identified that defined the closest associations with ACR responses in pts with inadequate response to MTX and high disease activity at baseline (mean DAS28 6.9). Sensitivities/NPVs were very high overall. Association with ACR20 was relatively strong. Association with ACR50/70 was weaker. Further studies are needed to analyze different pt populations, including those with lower disease activity at baseline. References: 1. Arthritis Rheum 2008; 58(11):3319–29. 2. Classification And Regression Trees (CART) software, Salford Systems, CA, USA Disclosure of Interest: M. Schiff Grant/Research support from: UCB Pharma, Consultant for: UCB Pharma, K. Luijtens Employee of: UCB Pharma, O. Davies Employee of: UCB Pharma, Y. Yazici Consultant for: UCB PharmaCitation: Annals of the Rheumatic Diseases, volume 71, supplement 3, year 2012, page 655Session: Rheumatoid arthritis – prognosis, predictors and outcome (Abstracts accepted for publication )