Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis

Abstract

ObjectiveTo evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status.MethodsPatients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models.Results1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI.ConclusionA pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity.Trial registration numbersNCT01895309, NCT01936181 and NCT02167139

Baseline bony erosions and time-averaged DAS28 predict discontinuation of TNF inhibitors in rheumatoid arthritis

“…In addition to reducing disease activity, another important treatment target in RA is the prevention of joint destruction, as joint destruction is irreversible and significantly reduces patient quality of life 11 . Long-term TNFi treatment in patients with early RA was found to slow radiographic structural damage 12 , and the achievement of remission by TNFi treatment showed beneficial effects on the radiographic progression of RA 13 . To date, however, the effect of baseline radiographic destruction in RA on TNFi retention rate has not been determined.…”

Validation of the adjusted multi-biomarker disease activity score as a prognostic test for radiographic progression in rheumatoid arthritis: a combined analysis of multiple studies

“…Preventing new joint damage remains an important goal for RA patient management. Although biologic agents have reduced the amount of joint damage progression observed in clinical trials and in practice, progression occurs in some patients receiving biologic therapy [3][4][5][6][7][8]. In addition, biologic therapy is not always initiated promptly in patients with inadequate response to a conventional disease-modifying anti-rheumatic drug (DMARD) [9].…”