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.
1. [120] - 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.
Orrin M. Troum, MD1,Charles G. Peterfy, MD, PhD2,Jeffrey L. Kaine, MD3,Carol Chung4,Andrew Anisfeld4,Ewa Olech, MD5,Philip G. Conaghan, MD, PhD6. 1University of Southern California, Santa Monica, CA, Santa Monica, CA,2Spire Sciences and Synarc, San Francisco, CA, Kentfield, CA,3Sarasota Arthritis Research Center, Sarasota, FL, Sarasota, FL,4Genentech, a member of the Roche Group, South San Francisco, CA,5Oklahoma University Health Sciences Center, Oklahoma City, OK, Oklahoma City, OK,6University of Leeds, Leeds, United Kingdom, Leeds
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 will experience 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.
Keywords: rheumatoid arthritis, treatment, tocilizumab, imaging techniques
Disclosure:
- Orrin Troum:
Abbott Laboratories: Research grants, Consulting fees, Speakers' bureau
Amgen Inc.: Research grants, Consulting fees, Speakers' bureau
Bristol-Myers Squibb: Research grants, Speakers' bureau
Centocor, Inc.: Research grants, Consulting fees
Novartis Pharmaceuticals Corporation: Research grants
Takeda: Consulting fees, Speakers' bureau
Pfizer Inc: Research grants, Consulting fees, Speakers' bureau
Proctor and Gamble: Speakers' bureau
Roche: Research grants, Consulting fees, Speakers' bureau
UCB, Inc.: Research grants, Consulting fees - Charles Peterfy:
Abbott Laboratories: Consulting fees
Amgen Inc.: Consulting fees
Biogen Idec: Consulting fees
Bristol-Myers Squibb: Consulting fees
Celgene: Consulting fees
Centocor, Inc.: Consulting fees
Lilly USA, LLC.: Consulting fees
Novartis Pharmaceuticals Corporation: Consulting fees
Crescendo: Consulting fees
Genentech: Consulting fees
Spire Sciences, LLC: Stock, stock options or bond holdings, Employment (full or part-time), Ownership or partnership
Pfizer Inc: Consulting fees
Rigel Pharma: Consulting fees
Roche: Consulting fees
Synarc, Inc.: Stock, stock options or bond holdings, Ownership or partnership
UCB, Inc.: Consulting fees
Wyeth Pharmaceuticals: Consulting fees - Jeffrey Kaine:
Amgen Inc.: Speakers' bureau
Bristol-Myers Squibb: Speakers' bureau
Novartis Pharmaceuticals Corporation: Speakers' bureau
UCB, Inc.: Speakers' bureau - Carol Chung:
Genentech: Employment (full or part-time) - Andrew Anisfeld:
Genentech: Employment (full or part-time) - Ewa Olech:
Biogen Idec: Research grants, Speakers' bureau
Bristol-Myers Squibb: Speakers' bureau
Centocor, Inc.: Research grants
Bio-rad: Research grants
Crescendo: Research grants
Genentech: Research grants, Consulting fees, Speakers' bureau
Pfizer Inc: Consulting fees
Roche: Research grants, Consulting fees
UCB, Inc.: Research grants, Consulting fees, Speakers' bureau
Vertex: Research grants - Philip Conaghan:
AstraZeneca: Speakers' bureau
Bristol-Myers Squibb: Speakers' bureau
Centocor, Inc.: Speakers' bureau
Merck Pharmaceuticals: Speakers' bureau
Novartis Pharmaceuticals Corporation: Speakers' bureau
Bioiberica: Speakers' bureau
Pfizer Inc: Research grants, Speakers' bureau
Roche: Speakers' bureau