Improvements in patient-reported outcomes and workplace and household productivity following 52 weeks of treatment with certolizumab pegol in combination with methotrexate in DMARD-naïve early rheumatoid arthritis patients: Results from the C-early randomized, double-blind, controlled phase 3 study

BACKGROUND:

Rheumatoid arthritis (RA) leads to high burden on patient (pt) physical function, quality of life (QoL) and work disability. Improvements in pt-reported outcomes (PROs)1 and workplace and household productivity2 with certolizumab pegol (CZP)+MTX were reported in established RA. Here we report results from C-EARLY, a phase 3 study of CZP+MTX in DMARD-naïve pts with early active RA.

OBJECTIVES:

To assess the effect of CZP+MTX vs placebo (PBO)+MTX on PROs, workplace and household productivity, and need for help with daily activities in DMARD-naïve pts with early active RA. Methods: Pts in this multicenter, double-blind, randomized study (NCT01519791) were DMARD-naïve, had early, active RA.: <1yr diagnosis at baseline (BL), fulfilling 2010 ACR/EULAR criteria; ≥4 swollen and ≥4 tender joints; DAS28[ESR]≥3.2; CRP≥10mg/L and/or ESR≥28mm/hr, rheumatoid factor or ACPA positive. Pts were randomized 3:1 to CZP (400mg Wks 0, 2, 4 then 200mg Q2W to Wk52)+MTX or PBO+MTX. MTX was initiated at 10mg/wk and increased up to 25mg/wk by Wk8, maximum tolerated dose was maintained to Wk52. Changes from BL in HAQ-DI, PtGADA, Pain VAS, % pts achieving normative physical function (HAQ-DI≤0.5), health-related QoL (SF-36, EQ-5D-3L) and workplace and household productivity (Work Productivity Survey [WPS]3) were assessed. At Wk52 changes from BL were analyzed using ANCOVA (LOCF imputation); categorical variables were analyzed using logistic regression (non-responder imputation); WPS responses (LOCF imputation) were compared using a nonparametric bootstrap-t method. Need for regular assistance in usual activities was summarized descriptively.

RESULTS:

660 (CZP+MTX) and 219 (PBO+MTX) pts were randomized; 655 vs 213 in the full analysis set (pts with BL and post-BL DAS28[ESR]). BL characteristics were balanced between study arms. BL disease severity was high: mean (SD) HAQ-DI 1.6 (0.6), Pain VAS 66.1 (22.4), PtGADA 65.3 (22.0) (Table A), DAS28[ESR] 6.7 (0.9), months since diagnosis 2.9 (4.3). 52% of pts were employed at BL (Table B). At Wk52, greater PRO improvements were observed with CZP+MTX vs PBO+MTX (Table A). CZP+MTX pts reported greater improvements vs PBO+MTX in household productivity, and lower need for assistance in usual activities. Employed CZP+MTX pts reported reductions in absenteeism and presenteeism vs PBO+MTX (Table B).

CONCLUSIONS:

In DMARD-naïve early RA pts, CZP+MTX showed greater improvements at 1yr in physical function, pain, disease activity, fatigue and health-related QoL, improved workplace and household productivity, and reduced need for assistance with regular activities compared to PBO+MTX. (Table Presented).