TOCILIZUMAB REDUCES SYNOVITIS WITHIN 2 WEEKS AND PRE-EROSIVE OSTEITIS WITHIN 12 WEEKS IN PATIENTS WITH RA: RESULTS FROM A MULTI-SITE LOW-FIELD MRI STUDY

O. Troum1, C. Peterfy2, J. Kaine3, B.-M.M. Day4, T. Woodworth5, P.G. Conaghan6 1University of Southern California, Santa Monica; 2Spire Sciences and Synarc, San Francisco; 3Sarasota Arthritis Research Center, Sarasota; 4Genentech, a member of the Roche group, South San Francisco, United States; 5Roche, Welwyn; 6University of Leeds, Leeds, United Kingdom

Background: IL-6R blockade with tocilizumab (TCZ) inhibits progression of radiographic joint damage in patients (pts) with RA within 6 mos. However, clinical and biochemical markers of disease activity show improvement 2 wks after initiation of TCZ. Synovitis and, particularly, osteitis have been shown on magnetic resonance imaging (MRI) to be strong predictors of radiographic progression of joint damage in pts with RA.

Objectives: To examine early effects of TCZ on synovitis and osteitis in pts with erosive RA who were inadequate responders to methotrexate (MTX).

Methods: As part of a randomized, double-blind, phase 3b study (ACT-RAY) that added TCZ to MTX versus switching to TCZ monotherapy, 63 RA pts on stable MTX were randomized to continue stable MTX or to receive placebo; both arms also received TCZ (8 mg/kg IV) every 4 wks. In this substudy, 0.2T extremity MRI of one hand (metacarpophalangeal joints [MCP] 1-5) and wrist was acquired at baseline and at wks 2 and 12. MR images underwent quality control and were scored by two radiologists using a RAMRIS method blinded to visit order. Blinded data from both TCZ arms were pooled and analyzed.

Results: Distribution of change scores was skewed. At wk 2, 44% of pts had improved synovitis scores and 7% of pts had improved scores ≥ smallest detectable change (SDC). Median changes from baseline in RAMRIS scores are shown in the table. At wk 12, 65% of pts had improved synovitis scores and 32% of pts had improved ≥SDC (1.7) (Table). By wk 12, median osteitis score improved from baseline and 28% of pts had improved ≥SDC (3.0) (Table). Median erosion score did not change at either time point, but 10 pts showed erosion score change ≥SDC (2.2) (7 regressed, 3 progressed) at wk 12. Osteitis developed in 2 normal joints with persistent synovitis, but no new erosions or synovitis developed in normal joints.

Conclusion: TCZ reduced synovitis in only 2 wks and pre-erosive osteitis within 12 wks of treatment initiation. Early MRI evidence of improvement with TCZ is consistent with inhibition of X-ray joint damage at 1 year.
Disclosure of Interest: O. Troum Grant/Research Support from: Roche, Amgen, Abbott, Centocor, BMS, UCB, Pfizer, Novartis, Consultant for: Roche, Amgen, Abbott, Centocor, UCB, Pfizer, Takeda, Speakers Bureau: Amgen, Abbott, BMS, Pfizer, Roche, Proctor & Gamble, Takeda, UCB, C. Peterfy Shareholder of: Spire Sciences, Synarc, Consultant for: Abbott, Amgen, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, Roche, Wyeth, Centocor, Genentech, Synarc, Bioclinica, Icon Medical Imaging, Employee of: Spire Sciences, J. Kaine Speakers Bureau: Bristol-Myers Squibb, Novartis, Amgen, UCB, Genentech, B.-M. Day Employee of: Genentech, division of Roche, T. Woodworth Employee of: Roche, P. G. Conaghan Grant/Research Support from: Pfizer, Speakers Bureau: Abbott, AstraZeneca, BMS, Centocor, Merck, Novartis, Pfizer, Roche

Citation: Ann Rheum Dis 2010;69(Suppl3):98

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