Impact of certolizumab pegol on patient-reported outcomes in rheumatoid arthritis and correlation with clinical measures of disease activity

Abstract

Introduction: The effect of certolizumab pegol (CZP) on patient-reported outcomes (PROs) was investigated in 1063 patients with rheumatoid arthritis (RA) from the REALISTIC trial (double-blind, placebo-controlled to week 12, open-label to week 28; randomized 4:1 [CZP:placebo]). Correlations between PROs and RA signs and symptoms, and the relative efficacy of these measures, were examined.

Methods: Adults with RA and an inadequate response to at least one disease-modifying antirheumatic drug were enrolled. PROs assessed included physical function (using the Health Assessment Questionnaire-Disability Index), pain, fatigue, sleep disturbance, Patient Global Assessment of Disease Activity (PtGA), Routine Assessment of Patient Index Data 3 (RAPID3), and Rheumatoid Arthritis Disease Activity Index (RADAI).

Results: Early significant and clinically meaningful improvements in all PROs were observed to week 12 with CZP vs. placebo and were maintained to the end of the trial (week 28). At week 12, up to one-third more CZP patients showed improvements compared with placebo that were greater than or equal to the minimal clinically important difference (MCID) in fatigue, sleep problems, pain, PtGA, RADAI, and RAPID3. The changes in PROs were correlated with clinical measures of disease activity, including the Disease Activity Score in 28 joints using C-reactive protein as well as tender and swollen joint counts.

Conclusions: Rapid improvements in PROs were seen in patients with RA treated with CZP. The magnitude of improvement exceeded the MCID in multiple domains and demonstrated that CZP improves aspects of health-related quality of life that are meaningful to patients and superior to placebo. PROs provide information complementary to clinical outcomes in assessment of treatment benefits.

Trial registration: ClinicalTrials.gov identifier: NCT00717236 . Registered on 15 July 2008.

Figures

Fig. 1

Adjusted mean least squares (LS) change from baseline in a fatigue, b sleep disturbance, c pain, and d Health Assessment Questionnaire-Disability Index (HAQ-DI) (intention-to-treat population, last observation carried forward; placebo n = 212, CZP n = 851). ap < 0.001 for CZP vs. placebo by analysis of covariance (ANCOVA); bp ≤ 0.01 for CZP vs. placebo by ANCOVA. CZP certolizumab pegol; FAS Fatigue Assessment Scale, MOS-SPI Sleep Problem Index II domain of the 12-item Medical Outcomes Study Sleep Scale, OLE open-label extension, VAS visual analogue scale

Fig. 2

Rheumatoid Arthritis Disease Activity Index total score (RADAI-TS) and Routine Assessment of Patient Index Data 3 (RAPID3) responses. a Adjusted mean least squares (LS) change from baseline in RADAI-TS. b Adjusted mean LS change from baseline in RAPID3. c Percentage of patients reporting improvements greater than or equal to the minimal clinically important difference (MCID) in RADAI. d Percentage of patients reporting improvements greater than or equal to the MCID in RAPID3 (intention-to-treat population, placebo n = 212, CZP n = 851). ap < 0.001 CZP vs. placebo by analysis of covariance; bp < 0.001 CZP vs. placebo by logistic regression. CZP certolizumab pegol, OLE open-label extension, PBO placebo

Fig. 3

Correlations between clinical measures of rheumatoid arthritis (RA) signs and symptoms and patient-reported outcomes in overall RA population (placebo and CZP combined, intention-to-treat population). CRP C-reactive protein, CZP certolizumab pegol, DAS28 Disease Activity Score in 28 joints, ESR erythrocyte sedimentation rate, FAS Fatigue Assessment Scale, HAQ-DI Health Assessment Questionnaire-Disability Index, JS joint score, MOS-SPI Sleep Problem Index II domain of the 12-item Medical Outcomes Study Sleep Scale, PtGA Patient Global Assessment of Disease Activity, RADAI Rheumatoid Arthritis Disease Activity Index, RAPID3 Routine Assessment of Patient Index Data 3, TS total score