Early Response As a Predictor of Long-term Remission in Dmard-naïve Patients with Severe, Active and Progressive Rheumatoid Arthritis Treated with Certolizumab Pegol in Combination with Methotrexate

BACKGROUND/PURPOSE:

In established rheumatoid arthritis (RA), a lack of response to treatment with certolizumab pegol (CZP) at early timepoints is associated with a low probability of achieving future target responses.1 The phase 3 C-EARLY study (NCT01519791) assessed efficacy and safety of CZP in inducing and maintaining a sustained clinical response and inhibiting radiographic damage in DMARD-naïve patients (pts) with active, severe, progressive RA with poor prognostic factors in comparison to MTX alone. Here, we examine the association between response to CZP+MTX in this pt population at an early visit (improvement/lack of improvement from baseline [BL] in DAS28[ESR] at Week [Wk] 12) and remission at Wk52.

METHODS:

This multicenter, double-blind, randomized study enrolled pts who were DMARD-naïve with active, severe, progressive RA (<1 year since diagnosis at BL, fulfilling 2010 ACR/EULAR criteria: ≥4 swollen and ≥4 tender joints; DAS28[ESR]≥3.2; CRP≥10 mg/L and/or ESR≥ 28 mm/hr, rheumatoid factor/ACPA positive). 879 pts were randomized 3:1 to CZP (400 mg at Wks 0, 2 and 4, then 200 mg every 2 wks to Wk52+MTX; n=660) or PBO+MTX Q2W (n=219). MTX was initiated at 10 mg/wk and increased to 25 mg/wk by Wk8, maximum tolerated dose per patient (optimized dose) was maintained to Wk52. Predictability analyses consisted of positive predictive value (PPV; probability of achieving Wk52 remission after achieving a Wk12 response) and negative predictive value (NPV; probability of failing to achieve Wk52 remission after failing to achieve a Wk12 response). Remission was defined as DAS28(ESR)<2.6; Wk12 responses analyzed were change from BL in DAS28(ESR) ≥0.6 and ≥1.2. Observed data were utilized for Wk12 responses; missing Wk52 values were imputed using non-responder imputation.

RESULTS:

At Wk52, 42.6% CZP+MTX pts vs 26.8% PBO+MTX pts achieved remission (DAS28[ESR] <2.6) (Table A). NPV of early responses was high (Table B): CZP+MTX-treated pts who did not achieve DAS28(ESR) improvements from BL ≥0.6 or ≥1.2 points at Wk12 had a high probability of not being in remission at Wk52; 92% and 93% respectively. Pts who did achieve an improvement from BL in DAS28(ESR) of ≥0.6 and ≥1.2 at Wk12 had 45% and 49% chance of Wk52 remission (Table B), respectively.

CONCLUSION:

DMARD-naïve pts with active, severe and progressive RA who failed to achieve DAS28(ESR) improvements at Wk12 after treatment with CZP+MTX were unlikely to be in remission at Wk52. These findings in DMARD-naïve pts are consistent with earlier reports in pts with established disease.