Background Treatment to lowest disease activity possible is the recommended treatment target for patients (pts) with rheumatoid arthritis (RA). However, radiographic damage and inflammatory biomarkers may differ based on treatment received and despite achieving the clinical target. Elevated inflammatory biomarkers have been associated with a higher risk of radiographic progression and extra-articular co-morbidities such as atherosclerosis.
Objectives To explore differences in radiographic progression, clinical efficacy, and inflammatory biomarker levels in MTX-naïve RA pts with DAS28(CRP) <3.2 at Wk52, after treatment with MTX only or with GLM+MTX.
Methods In GO-BEFORE, a randomized, double-blind, PBO-controlled trial, 637 MTX-naïve RA pts were randomized to PBO+MTX (n=160), golimumab (GLM) 100 mg+PBO (n=159), GLM 50 mg+MTX (n=159), and GLM 100 mg + MTX (n=159). At Wk52, the proportions of radiographic nonprogressors (change in vdH-S ≤0) and ACR20, ACR50, and ACR70 responders were determined. Changes from baseline to Wk52 in ESR, CRP, ICAM-1, IL-6, IL-8, and MMP-3 levels were measured. Outcomes were compared between the MTX only and the combined GLM (50 and 100 mg) +MTX groups among pts who did and did not have DAS28(CRP) <3.2 at Wk52. A similar analysis was performed for pts who did and did not achieve DAS28(CRP) <2.6.
Results Among pts with DAS28(CRP) <3.2, clinical responses were similar between treatment groups, however a greater proportion of GLM+MTX-treated pts were radiographic nonprogressors vs. MTX only (p<0.05). Significantly greater improvements from baseline were also noted in levels of ICAM-1, IL-6, and IL-8 in GLM+MTX-treated pts (table). Among non-DAS28(CRP) <3.2 pts, no statistical differences were observed between treatment groups in radiographic, clinical efficacy, or biomarker outcomes. Overall, DAS28(CRP) <3.2 pts had better outcomes compared to those not achieving this threshold, regardless of treatment received. In the DAS28(CRP) <2.6 analysis, greater improvements in biomarker levels were also observed for those attaining target on MTX+GLM; however, difference in radiographic nonprogression did not reach significance. Pts not achieving DAS28(CRP) <2.6, nevertheless, showed significant radiographic nonprogression when on GLM+MTX compared to MTX alone.
Conclusions Patients who attain DAS28(CRP) <3.2 on GLM+MTX exhibit greater radiographic nonprogression and suppression of ICAM-1, IL-6, and IL-8 compared to those on MTX alone at 1 yr. The potential benefits, beyond clinical response, of achieving pre-specified treatment goals with a TNF inhibitor may deserve further evaluation.
Disclosure of Interest G. Karpouzas Consultant for: Janssen, Speakers bureau: Janssen, P. Emery Grant/research support: Janssen, Consultant for: Janssen, R. Fleischmann Grant/research support: Janssen, Consultant for: Janssen, S. Xu Employee of: Janssen Research & Development, LLC., E. Hsia Employee of: Janssen Research & Development, LLC.