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.


Assessment of Inflammation and Damage by MRI in Established RA Patients with Methotrexate Inadequate Response Receiving Golimumab: Results of the GO-FORWARD Trial.

Conaghan3,  Philip G., Emery4,  Paul, Ostergaard5,  Mikkel, Keystone8,  Ed C., Genovese7,  Mark C., Klareskog6,  Lars, Xu1,  Weichun

Centocor Research and Development, Inc.
Centocor Research and Development, Inc./Univ. of Pennsylvania School of Medicine, Malvern, PA
Chapel Allerton Hospital, Leeds, United Kingdom
Chapel Allerton Hospital, Leeds, United Kingdom
Copenhagen University Hospital at Glostrup and Hvidovre
Karolinska University Hospital, Stockholm, Sweden
Stanford University, Sunnyvale, CA
University of Toronto, Toronto, ON, Canada

Background:

Previously reported results of the GO-FORWARD trial have shown the beneficial effects of adding the human monoclonal antibody golimumab (GLM) on signs and symptoms and physical function in an established RA cohort with methotrexate (MTX) inadequate response. Magnetic resonance imaging (MRI) provides a sensitive tool for the objective assessment of both inflammation and damage.

Objective:

To evaluate the effect of GLM on the inflammation and structural damage detected by MRI in pts with active RA despite MTX.

Methods:

Patients (n=444) were randomly assigned to receive placebo (PBO) + MTX, GLM 100mg + PBO, GLM 50mg + MTX, or GLM 100mg + MTX. A subset of study sites capable and willing participated in the MRI substudy. All pts from each substudy site were eligible for the substudy (n=240). GLM and PBO were administered via subcutaneous injection q4 wks. At wk16, pts in the PBO + MTX, GLM 100mg + PBO, and GLM 50mg + MTX groups with <20% improvement in both tender and swollen joint counts entered early escape to receive GLM 50mg + MTX, GLM 100mg + MTX, and GLM 100mg + MTX, respectively. The main comparison was between the combined GLM + MTX and PBO + MTX groups. MRIs of the pt's dominant wrist and metacarpophalangeal joints were obtained at baseline and wks12, 24, 52 and 104 using 1.5T MRI with contrast enhancement. Results through wk24 are presented here. Images were scored by 2 independent expert readers who were blinded to image time point or sequence, pt identity, or treatment group. Readers scored synovitis (0–21), bone erosions (0–230), and bone edema (osteitis; 0–69) using the Rheumatoid Arthritis MRI Scoring (RAMRIS) system; the average of each RAMRIS score provided by the readers was used in the analysis. Pts who entered early escape at wk16 had their last observation carried forward in the MRI analysis at wk24.

Results:

Significant improvements in synovitis and bone edema (osteitis), which are known prognosticators of future structural damage, were observed in the combined GLM + MTX groups versus the PBO + MTX group. The minimal changes in bone erosions observed in all treatment groups (Table), precluded the adequate evaluation of GLM's effect on bone erosions, which is consistent with previously published radiographic data. This could be because the overall GO-FORWARD study population had less active inflammation at baseline (median CRP concentrations ranging from 0.60 to 0.95mg/dL), indicating this population would have minimal changes in bone erosion.

Conclusion:

Results of MRI assessments showed that GLM + MTX significantly improved synovitis and bone edema (osteitis) relative to PBO plus MTX as early as wk12 and also at wk24. The effect of GLM on bone erosions could not be determined by semi-quantitative scoring in this population of RA pts who had minimal changes in bone erosion during this study.

Table. RAMRIS scores including at baseline and changes from baseline to weeks 12 and 24

RAMRIS scores: values are meandian (interquartile range)Placebo + MTX (n = 72)GLM 100mg + PBO (n = 72)GLM 50mg + MTX (n = 47)GLM 100mg + MTX (n = 49)Combined GLM + MTX (n = 96)
Synovitis*     
  Baseline6.7 6.8 (3.3, 9.30)7.3 7.5 (2.5, 10.5)7.6 7.8 (4.1, 10.5)6.3 6.6 (3.0, 8.5)7.0 7.0 (4.0, 9.5)
  Week 12-0.2 -0.5 (-1.5, 1.5)-0.8 -0.3 (-2.0, 0.5)-2.0 -2.0 (-3.0, -0.5)-1.5 -2.0 (-3.2, 0.5)-1.8 -2.0 (-3.2, 0.0)
    p value 0.299<0.0010.014<0.001
  Week 24-0.4 -0.5 (-1.5, 1.0)-1.0 -1.0 (-1.5, 0.0)-1.9 -1.8 (-3.0, -0.5)-2.0 -1.0 (-4.5, 0.0)-1.9 -1.0 (-3.1, -0.33)
    p value 0.202<0.0010.003<0.001
Bone edema (Osteitis)     
  Baseline7.1 2.0 (0.0, 12.0)6.9 2.3 (0.0, 10.0)7.6 4.0 (0.5, 12.5)6.0 2.0 (0.0, 7.0)6.8 2.5 (0.0, 11.8)
  Week 120.2 0.0 (-1.0, 1.5)-2.1 0.0 (-2.1, 0.0)-2.8 -0.5 (-4.5, 0.0)-1.3 0.0 (-1.5, 0.0)-2.0 -0.5 (-2.1, 0.0)
    p value 0.0070.0020.0710.003
  Week 240.7 0.0 (-0.5, 0.5)-1.3 0.0 (-1.5, 0.0)-2.6 -0.5 (-4.1, 0.0)-0.9 0.0 (-1.6, 0.0)-1.7 0.0 (-2.2, 0.0)
    p value 0.109<0.0010.1770.004
Bone erosion     
  Baseline25.5 12.8 (8.0, 28.3)25.2 17.4 (5.5, 35.5)23.9 11.0 (5.5, 29.0)22.1 13.5 (6.0, 20.7)23.0 12.5 (6.0, 25.0)
  Week 12-0.8 0.0 (-0.5, 0.1)0.5 0.0 (0.0, 0.5)-1.3 0.0 (-0.5, 0.0)-0.8 0.0 (-0.1, 0.4)-1.0 0.0 (-0.5, 0.0)
    p value 0.0380.3640.3200.899
  Week 24-0.5 0.0 (-0.5, 0.0)0.4 0.0 (0.0, 0.0)-1.1 0.0 (-0.5, 0.0)-0.8 0.0 (-0.1, 0.2)-0.9 0.0 (-0.2, 0.0)
    p value 0.1390.2070.6800.622
*Given that several sites did not have the capability to obtain postgadolinium images, synovitis evaluations of the wrist and MCP joints were obtained in 56, 53, 38, and 39 patients in the PBO + MTX, 100 mg + PBO, 50 mg + MTX, and 100 mg + MTX groups, respectively.

To cite this abstract, please use the following information:
Conaghan, Philip G., Emery, Paul, Ostergaard, Mikkel, Keystone, Ed C., Genovese, Mark C., Klareskog, Lars, et al; Assessment of Inflammation and Damage by MRI in Established RA Patients with Methotrexate Inadequate Response Receiving Golimumab: Results of the GO-FORWARD Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1097
DOI: 10.1002/art.28864

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