982 - Utility of Patient-Reported Outcomes in Assessing Treatment Response in Rheumatoid Arthritis: Humira® Efficacy Response Optimization (HERO) Trial

F. Wolfe1, K. Michaud1, T. Pincus2, J. D. Kent3, A. L. Pangan3. 1National Data Bank for Rheumatic Diseases, Wichita, KS; 2Vanderbilt University, Nashville, TN; 3Abbott, Abbott Park, IL
Presentation Number: 982

PURPOSE: It remains uncertain as to which variables best measure treatment effect. In the HERO trial, we used the rapid improvement that occurs with anti-TNF therapy to evaluate response variables two weeks after starting adalimumab (ADA). Early assessments do not include improvement that may occur with time as a function of regression to the mean, leaving only treatment and placebo (PBO) effects to influence results.
METHODS: HERO was a randomized, double-blind, PBO-controlled, multi-center, Phase IV study of ADA 40 mg every other week (wk) in pts with active RA, with emphasis on pt-reported outcomes (PROs) and early response. Pts received a blinded dose of study drug, followed by 10 wks of open-label (OL) ADA at Wk 2. Physician measures, C-reactive protein (CRP) and PROs were collected at baseline, Wks 2, 4, and 12. Pt Activity Score (PAS) was based on Health Assessment Questionnaire (HAQ) disability score, pain on a visual analog scale (VAS) and pt global VAS. We evaluated Wk 2 blinded data to see how well each variable captured ADA or PBO effect. To assess magnitude of treatment effect, we calculated effect sizes (ES) (standardized responses) at Wk 2 for PBO (ES[P]) and for ADA, labelled ES[T+P] as there is a true (T) treatment effect and a PBO component (P) in each observed response. We calculated Kendall’s Tau-a between type of treatment (ADA or PBO) and change in study variables. Variables with higher Tau-a scores have greater ability to detect treatment effect. The area under the Receiver Operating Curve (AUC), a standardized multivariable measure of treatment effect, was used to compare groups of variables.
RESULTS: There were 1891 pts evaluated. In the ADA arm, ACR 20/50/70 response rates were 24/13/9 at Wk 2 and 58/47/40 at Wk 12. Greatest PBO effect (ES[P]) was found for DAS-28, physician global (MD global), VAS stiffness and tender joint count (TJC) (Table 1). Only CRP was without PBO effect. ADA treatment ES (ES [T+P]) was greatest for MD global, DAS-28 and VAS stiffness. As assessed by Tau-a, CRP, PAS and VAS pain best distinguished ADA treatment effects. The AUC was 0.64 for either PAS or DAS-28. However, combining PAS+CRP increased the AUC to 0.71.
CONCLUSIONS: Physician and pt-based measures have PBO components that can limit their usefulness. At Wk 2 of this study, certain pt-based measures were equal or superior to individual physician variables and DAS-28 in determining efficacy, due to increased PBO effect in physician measures. The PAS + CRP combination is an effective and less biased way to evaluate early improvement and appears to be suitable for clinical practice use.
All pts.
All pts
(Week 12)
ES (T + P)
(Week 2)
ES (P)
(Week 2)
(Week 2)
CRP (mg/dL)1.400.700.47-0.010.213
PAS (0-10)5.072.990.540.160.142
VAS Pain (0-10)5.793.220.600.170.139
VAS Stiffness (0-10)5.592.750.620.240.123
Pt. Global (0-10)
MD Global (0-10)5.652.430.720.290.116
HAQ-II (0-3)1.190.830.320.090.100
MD HAQ (0-3)0.940.610.340.110.099
HAQ (0-3)1.240.820.310.110.094
VAS Fatigue (0-10)5.783.540.350.150.087
SJC (0-28)9.704.460.410.210.085
TJC (0-28)
VAS QOL (0-10)0.760.82-0.30-0.04-0.075
FACIT Fatigue (0-52)28.0734.82-0.35-0.14-0.078

F. Wolfe, The NDB has received research support from Abbott, Amgen, Bristol-Myers-Squibb and Centocor, 2 Research grants.