Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Early Reductions in Tissue Inflammation with Tocilizumab As Either Monotherapy or in Combination with Methotrexate: 12-Week Unblinded Results From a Magnetic Resonance Imaging Substudy of a Randomized Controlled Trial.

Conaghan1,  Philip G., Peterfy2,  Charles G., DiCarlo2,  Julie, Olech3,  Ewa, Alberts4,  Alan R., Alper5,  Jeffrey A., Devenport6,  Jenny

NIHR-Leeds Biomedical Research Unit and Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom
Spire Sciences LLC, San Francisco, CA
Oklahoma Medical Research Foundation, Oklahoma City, OK
West Broward Rheumatology Associates, Inc., Tamarac, FL
Jeffrey Alper MD Research, Naples, FL
Genentech, South San Francisco, CA
USC Keck School of Medicine, Santa Monica, CA

Background/Purpose:

Tocilizumab (TCZ) monotherapy (MONO) has been shown to be superior to methotrexate (MTX) in achieving clinical reduction of disease activity in rheumatoid arthritis (RA).1 A 24-week (wk) interim analysis of the double-blind phase 3b ACT-RAY study2 showed no additional clinical benefit from adding MTX to TCZ vs switching to TCZ+PBO in patients with an inadequate response to MTX. It is important to determine if tissue inflammation, an important predictor of radiographic damage, is reduced in an analogous pattern. While MRI results from the blinded TCZ±MTX population have been reported,3 this analysis examined effects of MRI measures of synovitis (SYN), osteitis (OST), and erosion (ERO) through wk 12 after therapy initiation by treatment assignment in patients with erosive RA.

Methods:

In the ACT-RAY study, RA patients with inadequate response to MTX were randomized to continue stable MTX or receive placebo (PBO), both in combination with TCZ 8 mg/kg IV every 4 wks. In a substudy of this trial (N=63), 0.2T extremity MRI of one hand (metacarpophalangeal joints 1–5) and wrist was acquired at baseline (BL) and wks 2, 12, and 52. MRIs were quality-controlled and scored by 2 blinded radiologists by a RAMRIS method. Change in scores from BL through wk 12 for the TCZ+MTX and TCZ+PBO groups in this substudy are compared to evaluate early effects on joint inflammation between the two treatment regimens.

Results:

BL mean RAMRIS scores showed high disease severity and burden in both groups (Table). Decreases in SYN and OST were observed at wk 2 and became statistically significant in both groups by wk 12. No significant changes from BL in mean ERO score emerged (Table). BL osteitis scores were higher in the PBO group; the proportion of patients who experienced improvements >=Smallest Detectable Change (SDC) for both SYN and OST was higher in the PBO group than in the MTX group. Similar numbers of patients experienced ERO progression vs regression in each group (Table). During this period, no patient in the TCZ+PBO group and only 1 (3.3%) patient in the TCZ+MTX group developed a newly eroded bone.

Table. Mean Values and SDC-Based Classification of RAMRIS Scores

Mean RAMR[squ]S ScoreBL (n = 31)Wk 2 (n = 31)TCZ+MTX (N = 31)Wk 12 (n = 30)BL to Wk 12 D (95% CI) (n = 30)BL (n = 32)Wk 2 (n = 32)TCZ+PBO (N = 32)BL to Wk 12 D (95% CI) (n = 29)
BL to Wk 2 D (95% CI) (n = 31)BL to Wk 2 D (95% CI) (n = 32)Wk 12 (n = 29)   
SYN7.27.1-0.1 (-0.5, 0.3)6.3-0.9* (-1.6, -0.2)7.46.5-0.9† (-1.5, -0.4)5.7-1.9‡ (-2.8, -1.0)
OST7.87.6-0.2* (-1.3, 0.9)4.4-3.6† (-6.5, -0.7)11.110.3-0.7 (-1.8, 0.3)5.5-5.1* (-8.6, -1.6)
ERO19.419.40.0 (-0.4, 0.5)19.2-0.3 (-1.2, 0.6)16.016.20.2 (-0.0, 0.5)16.60.0 (-0.6, 0.6)
*P<0.01,P<0.001;P<0.0001.
Wilcoxon Signed Rank test for no change from BL within group; Percentile interval: 95% CI of mean change from BL within group.
TCZ+MTX (N=30) n (%)TCZ+PBO (N=29) n (%)
Classification Derived from SDCa at Wk 12Regressors (Change <= SDC)Progressors (Change >= SDC)Regressors (Change <= SDC)Progressors (Change >= SDC)
SYN7 (23.3)1 (3.3)11 (37.9)0
OST6 (20.0)09 (31.0)1 (3.4)
ERO3 (10.0)2 (6.7)3 (10.3)2 (6.9)
a SDC values at wk 12:
SYN: 1.71
OST: 4.27
ERO: 1.51

Conclusion:

These MRI data (previously blinded for TCZ±MTX, but now unblinded to evaluate TCZ+MTX and TCZ+PBO groups separately) demonstrate that TCZ is associated with early suppression of SYN and OST, with no mean increase in ERO score observed through wk 12. The similarities in MRI findings between TCZ+PBO and TCZ+MTX groups suggest that continuation of MTX in combination with TCZ or switching to TCZ MONO are equally beneficial for early suppression of joint inflammation. TCZ MONO may be an appropriate alternative to TCZ+MTX in patients who are intolerant or unwilling/unable to take MTX.

References

1.Jones, G et al. Ann Rheum Dis. 2010;69:88–96.

2.Dougados, M et al. Presented at the EULAR Annual Congress; May 25–28, 2011; London, UK.

3.Troum, O et al. Presented at the EULAR Annual Congress; May 25–28, 2011; London, UK.

To cite this abstract, please use the following information:
Conaghan, Philip G., Peterfy, Charles G., DiCarlo, Julie, Olech, Ewa, Alberts, Alan R., Alper, Jeffrey A., et al; Early Reductions in Tissue Inflammation with Tocilizumab As Either Monotherapy or in Combination with Methotrexate: 12-Week Unblinded Results From a Magnetic Resonance Imaging Substudy of a Randomized Controlled Trial. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :434
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