A Randomized Trial Comparing Disease Activity Measures for the Assessment and Prediction of Response in Rheumatoid Arthritis Patients Initiating Certolizumab Pegol

Abstract

Objective: The aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to compare the patient-reported Routine Assessment of Patient Index Data 3 (RAPID-3) instrument with the investigator-based Clinical Disease Activity Index (CDAI) for assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 (coprimary end points).

Methods: Patients received 400 mg of CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks thereafter. Patients were randomized 1:1 to assessment with the RAPID-3 or the CDAI. Responder classification was performed at week 12; treatment response was defined as a score of ≤6 or a 20% improvement over baseline on the RAPID-3 or a score of ≤10 or a 20% improvement over baseline on the CDAI. Long-term treatment success was defined as a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.2 at week 52. Comparisons were made for the coprimary end points using noninferiority methods. Patients with improvement of <1 on the CDAI score or with no improvement on the RAPID-3 score at week 12 or patients with high levels of disease activity (CDAI score >22 or RAPID-3 score >12) at 2 consecutive visits were withdrawn from the study.

Results: Patients had longstanding disease (mean 8.9 years) and high levels of disease activity (mean scores of 6.3 on the DAS28-ESR, 16.1 on the RAPID-3, and 40.2 on the CDAI). Previous anti-tumor necrosis factor therapy had failed in 55.5% of them. At week 12, a total of 64.7% (by RAPID-3) and 76.4% (by CDAI) of the patients were classified as responders (difference of -11.9% [95% confidence interval -18.4%, -5.3%]). At week 52, a total of 31.5% (by RAPID-3) and 32.3% (by CDAI) of the responders achieved a low level of disease activity on the DAS28-ESR (difference of -1.3% [95% confidence interval -9.3%, 6.6%]).

Conclusion: The CDAI classified more patients as CZP responders at week 12 than did the RAPID-3. Although these outcome measures were not statistically comparable, the positive predictive value for low disease activity at week 52 was similar. As these tools cover differing domains of therapy response, further evaluation for clinical disease activity assessments and treatment decisions is needed.

Figure 1

Study design (A) and disposition of the study patients (B). ^aResponders according to the Clinical Disease Activity Index (CDAI) were defined as patients with a CDAI score of ≤10 or a 20% improvement over baseline. ^bResponders according to the Routine Assessment of Patient Index Data 3 (RAPID‐3) were defined as patients with a RAPID‐3 score of ≤6 or a 20% improvement over baseline. RA = rheumatoid arthritis; DMARD = disease‐modifying antirheumatic drug; TNF = tumor necrosis factor; DAS28‐ESR = Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; LDA = low disease activity; CZP = certolizumab pegol; Q2W = every 2 weeks.

Figure 2

Predicted response at week 12 and proportion of week 12 predicted responders with low levels of disease activity according to the DAS28‐ESR at week 52 and in remission/low disease activity at week 12 and week 52 (full analysis set; nonresponder imputation). A, Proportion of patients in remission and low disease activity according to the DAS28‐ESR at week 12 and week 52. B, Proportion of week 12 responders and week 12 responders with low disease activity according to the DAS28‐ESR at week 52. The difference in proportions for the RAPID‐3 arm minus the CDAI arm was analyzed using nonparametric analysis of covariance with the assessment tool as the factor and with the baseline DAS28‐ESR, sex, age, prior anti‐TNF use, and duration of RA (<2 or ≥2 years) as covariates. 95% CI = 95% confidence interval (see Figure 1 for other definitions).

Figure 3

Change in the DAS28‐ESR and the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) by week 12 responder status (full analysis set; nonresponder imputation). A, Mean change from baseline in the DAS28‐ESR by week 12 responder status. B, Proportion of ACR20 responders by week 12 responder status. MID = minimum clinically important difference (see Figure 1 for other definitions).