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.
VariableMean
All pts.
(Baseline)
Mean
All pts
(Week 12)
ES (T + P)
(Week 2)
ES (P)
(Week 2)
Tau-a
(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
DAS-283.892.550.630.290.135
VAS Stiffness (0-10)5.592.750.620.240.123
Pt. Global (0-10)5.283.000.500.140.118
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)12.285.220.400.230.068
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.