Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Baseline CRP Predicts Early Improvement in Synovitis, Osteitis, and Erosion on MRI in RA Patients Treated with Tocilizumab: Results from the ACT-RAY MRI Substudy.

Troum6,  Orrin M., Peterfy4,  Charles G., Kaine3,  Jeffrey L., Chung1,  Carol, Anisfeld1,  Andrew, Olech2,  Ewa, Conaghan5,  Philip G.

Genentech, a Member of the Roche Group, South San Francisco, CA
Oklahoma University Health Sciences Center, Oklahoma City, OK
Sarasota Arthritis Research Center, Sarasota, FL
Spire Sciences and Synarc, San Francisco, Kentfield, CA
University of Leeds, Leeds, United Kingdom
University of Southern California, Santa Monica, CA, Santa Monica, CA

Purpose:

IL-6R inhibition with tocilizumab (TCZ) inhibits progression of radiographic joint damage in patients (pts) with RA within 6 months. However, clinical and biochemical markers of disease activity, including CRP, and bone and cartilage turnover markers show improvement 2–4 weeks after TCZ initiation. Synovitis (SYN), particularly osteitis (OST), on magnetic resonance imaging (MRI) and elevated CRP levels have been shown to be strong predictors of radiographic progression of joint damage in patients with RA. This analysis examined early effects of TCZ on SYN, OST, and erosion (ERO) in pts with erosive RA who were inadequate responders to methotrexate (MTX-IR).

Methods:

As part of a randomized, double-blind, phase 3b study (ACT-RAY) in MTX-IR pts, 63 RA pts on stable MTX were randomly assigned to continue stable MTX or to receive placebo, both in combination with TCZ 8 mg/kg IV every 4 weeks. In this substudy, 0.2T extremity MRI of one hand (metacarpophalangeal joints [MCP] 1–5) and wrist was acquired at baseline and at weeks 2 and 12. MR images were quality controlled and scored by two radiologists using a RAMRIS method blinded to visit order. In this interim analysis, blinded data from both TCZ arms were pooled and analyzed. CRP values were measured at baseline and every 4 weeks.

Results:

By week 2, SYN scores improved in 44% of pts and improved >= smallest detectable change (SDC) in 7% of pts. By week 12, SYN and OST scores improved >=SDC in 32% and 28% of patients, respectively. Median ERO score did not change at either time point, but 10 pts showed ERO score change >=SDC (7 regressed [12%], 3 progressed [5%]) at week 12. Baseline CRP levels were variable, with a mean of 1.2 mg/dL (range 0.1–10.3); 93% of patients achieved normal CRP levels by week 12. Exploratory analysis stratifying MRI RAMRIS subscores by baseline CRP levels revealed that mean baseline SYN, OST, and ERO scores were numerically higher in patients with baseline CRP >=1.0 than in those with CRP <=0.3, or 0.3–1.0. Pts with high baseline CRP (>=1.0) were 1.7-, 7.2-, and 3.2-fold more likely to achieve improvements >=SDC in SYN, OST, and ERO, respectively, at week 12 than were pts with normal baseline CRP levels (<=0.3) (Table).

Conclusions:

TCZ reduced synovitis in only 2 weeks and pre-erosive OST within 12 weeks of treatment initiation. Pts with baseline CRP levels >=1.0 mg/dL were more likely than pts with baseline CRP levels <1 mg/dL to achieve improvements in MRI measures of inflammation and erosive activity, indicating that CRP may have the potential to predict which pts willexperience the greatest MRI improvements after treatment with TCZ. Analysis of the upcoming 52-week visit from this study will offer an opportunity to confirm this observation. MRI evidence of early improvement with TCZ is in line with prior demonstration of inhibition of X-ray joint damage at 1 year and the observation that baseline CRP predicts radiographic progression.

   Baseline CRP, mg/dL
  <=0.3>0.3-<1.0>=1.0Total
Mean baseline RAMRIS scoren19222263
 SYN6.66.59.47.5
 OST3.95.316.28.7
 ERO13.620.422.319.0
Pts with week-12 improvement >= SDC, %n16202157
 SYN25a2543a32
 OST6b3043b28
 ERO6c1019c12
SDC: SYN = 1.7, OST = 3.0, ERO = 2.2.a 43 is 1.7-fold greater than 25,b43 is 7.2-fold greater than 6.c19 is 3.2-fold greater than 6.

To cite this abstract, please use the following information:
Troum, Orrin M., Peterfy, Charles G., Kaine, Jeffrey L., Chung, Carol, Anisfeld, Andrew, Olech, Ewa, et al; Baseline CRP Predicts Early Improvement in Synovitis, Osteitis, and Erosion on MRI in RA Patients Treated with Tocilizumab: Results from the ACT-RAY MRI Substudy. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :120
DOI: 10.1002/art.27889

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