Background At 2 yrs, rituximab (RTX) plus methotrexate (MTX) has been shown to inhibit progressive joint damage (PJD) in patients (pts) with RA and an inadequate response to TNF inhibitors (TNF-IR).1 This 5-yr analysis assessed the impact of RTX on PJD in TNF-IR pts in the REFLEX open-label extension (OLE) study.
Methods In REFLEX, TNF-IR pts receiving MTX were randomized to placebo (PBO; n=209) or RTX (n=311).2 Pts subsequently transferred to an OLE study to receive RTX repeat treatment as clinically required. This post-hoc analysis was conducted on ITT pts with X-rays at baseline (BL) and 5 yrs. Pts randomized at BL to PBO who may have subsequently received RTX as rescue therapy (PBO-RTX group) and pts originally randomized to RTX (RTX group) were included. X-rays of hands and feet were read at BL and yrs (Y) 1, 4, and 5; all were rescored for this analysis (Sharp-Genant method) by trained radiologists who were blinded to group assignment and X-ray order. Missing data were imputed using linear extrapolation of progression observed from BL to last value prior to missing value.
Results The ITT population comprised 79 PBO-RTX and 105 RTX pts; 71 PBO-RTX pts were rescued with RTX during Y1, with 6 additional pts rescued after Y1. BL demographics and disease characteristics were balanced between groups, except disease duration (PBO-RTX 10.5 Y; RTX 13.5 Y). Pts in both groups received up to 12 (mean=5) RTX courses over the 5 yrs. In both groups, mean (SE) rate of change in modified Total Sharp Score (ΔmTSS) continued to decrease to Y5; change from BL at Y5 was 5.51 (0.95) for PBO-RTX pts and 3.21 (0.64) for RTX pts (table). Similar effects were observed for erosion scores and joint space narrowing. Annualized progression rate decreased from 2.08 (BL to Y1) to 0.89 (Y1 to Y4) and 0.25 (Y4 to Y5) in PBO-RTX pts, and from 0.91 to 0.56 and 0.33 for the same periods in RTX pts. Between Y4 and Y5, PBO-RTX pts showed similar rates of PJD to those originally randomized to RTX. A greater proportion of pts in the RTX group vs the PBO-RTX group showed no radiographic progression (ΔmTSS ≤0) at Y1 (48.0% vs 32.0%), a difference that remained at Y4 (32.4% vs 24.1%) and Y5 (32.4% vs 21.5%).
Conclusions This 5-yr analysis demonstrates that TNF-IR pts originally randomized to RTX had enhanced inhibition of PJD at 5 yrs vs those originally randomized to PBO (and later rescued with RTX). Both groups showed continued improvement in PJD inhibition over time, with PBO pts progressing more rapidly in Y1 than RTX pts. RTX pts were more likely to have no radiographic progression at Y1, Y4 and Y5. A delay of approximately 1 yr in RTX initiation appears to lead to an increased rate of PJD. Differences between the groups remained to 5 yrs.
Cohen et al. Ann Rheum Dis 2010;69:1158.
Cohen et al. Arthritis Rheum 2006;54:2793.
Disclosure of Interest E. Keystone Grant/Research support from: Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB, Consultant for: Abbott, AstraZeneca, Biotest, Bristol-Meyers Squibb, Centocor, Roche, Genentech, Merck, Nycomed, Pfizer, UCB, S. Cohen Grant/Research support from: Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB, Consultant for: Amgen, Bristol-Meyers Squibb, Roche/Genentech, Merck, Pfizer, P. Emery Consultant for: Pfizer, Merck, Abbott, BMS, Roche, Novartis, J. Kremer Grant/Research support from: Genentech, Roche, Consultant for: Genentech, Speakers Bureau: Genentech, M. Dougados Grant/Research support from: Roche, Abbott, Pfizer, BMS, UCB, Novartis, Merck, Consultant for: Roche, Abbott, Pfizer, BMS, UCB, Novartis, Merck, J. Loveless Consultant for: Roche, Speakers Bureau: Roche, C. Chung Employee of: Genentech, P. Wong Employee of: Genentech, P. Lehane Employee of: Roche Products Ltd, H. Tyrrell Employee of: Roche Products Ltd
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