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.


Golimumab and Methotrexate Combination Therapy Significantly Improves Synovitis, Osteitis and Bone Erosion Compared to Methotrexate AloneA Magnetic Resonance Imaging Study of Methotrexate-Nave Rheumatoid Arthritis Patients.

Ostergaard6,  Mikkel, Emery4,  Paul, Conaghan5,  Philip G., Fleischmann7,  Roy M., Xu2,  Weichun, Hsia3,  Elizabeth C., Beutler1,  Anna

Centocor Research and Development, Inc., Collegeville, PA
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, Hvidovre, Denmark
University of Texas SW Medical Center, Dallas, TX

Background:

In the GO-BEFORE study, golimumab (GLM) improved signs and symptoms of RA, improved physical function, and slowed the progression of structural damage in patients who were methotrexate (MTX) naïve.

Objective:

To evaluate the effect of GLM on the inflammation and structural damage detected by magnetic resonance imaging (MRI) in patients with RA who were MTX naïve.

Methods:

Patients (n=637) were randomly assigned to receive placebo (PBO) + MTX, GLM 100 mg + PBO, GLM 50 mg + MTX, or GLM 100 mg + MTX. A subset of study sites capable and willing participated in the MRI substudy. All patients from each substudy site were eligible for substudy participation (n=318). GLM and PBO were administered via subcutaneous injection every 4 weeks. The primary comparison was between the PBO + MTX and combined GLM + MTX groups. MRIs of the patient's dominant wrist and metacarpophalangeal joints were obtained at baseline and weeks 12, 24, 52, and 104 using 1.5T MRI with contrast enhancement. Results through week 24 are presented here. Images were scored by two independent expert readers blinded to image time point or sequence, patient identity, or treatment group. Readers scored synovitis (0–21), bone edema (osteitis) (0–69), and bone erosions (0–230), using the Rheumatoid Arthritis MRI Scoring (RAMRIS) system; the average of each RAMRIS score provided by the readers was used in the analysis.

Results:

Mean baseline RAMRIS bone edema and RAMRIS bone erosion scores were numerically slightly lower in the PBO than GLM groups. Significant improvements in RAMRIS synovitis, osteitis and bone erosions were observed at weeks 12 and 24 in the combined GLM + MTX groups relative to PBO + MTX (Table). Significant improvements in synovitis and bone edema were observed in both GLM + MTX dose groups at both weeks 12 and 24 versus the PBO + MTX group. Significantly less bone erosion progression was documented at week 12 for the GLM 50 mg + MTX group and at 24 weeks for both GLM + MTX doses. Comparison of radiographic data (using the van der Heijde modification of the Sharp score) within the MRI substudy patients (n=318) showed no significant difference between the PBO + MTX and combined GLM + MTX groups (mean ± SD changes from baseline to week 28 of 0.92 ± 2.96 and 0.49 ± 3.23, respectively; p=0.19), thus demonstrating MRI to be superior to x-rays in terms of sensitivity to changes in erosive progression.

Conclusion:

Results of this MRI substudy of the GO-BEFORE trial demonstrated that patients who received GLM + MTX had improvements in inflammation (synovitis and osteitis) and improvements in erosions exceeding those observed with PBO + MTX as early as week 12 and continuing through week 24, confirming the clinical and radiological findings previously reported for the overall study population. MRI assessment was superior to x-ray in terms of sensitivity to change in erosive progression.

RAMRIS scores:values are mean/median (interquartile range)Placebo+MTX (n = 82)GLM 100mg+PBO (n = 77)GLM 50mg+MTX (n = 78)GLM 100mg+MTX (n = 81)Combined GLM+MTX (n = 159)
Synovitis*     
Baseline8.8 8.5(5.0, 12.0)9.3 9.0(4.0, 14.5)10.3 10.5(7.0, 14.0)9.6 9.5(6.0, 13.5)9.9 10.0(6.5, 13.8)
Week 120.1 0.0(-1.0, 1.5)-1.8 -1.0(-3.5, -0.5)-1.7 -1.0(-2.5, -0.2)-2.2 -2.0(-4.0, 0.0)-1.9 -1.5(-3.5, 0.0)
p value <0.001<0.001<0.001<0.001
Week 24-1.0 -1.0(-1.6, 0.0)-1.6 -1.1(-2.5, 0.0)-2.2 -1.5(-3.5, -0.3)-2.7 -1.5(-4.5, -0.5)-2.5 -1.5(-4.0, -0.5)
p value 0.3440.0110.001<0.001
Bone edema (Osteitis)     
Baseline8.4 5.0(2.5, 11.5)10.6 6.5(1.5, 17.8)11.5 9.5(4.0, 17.0)9.5 7.0(2.0, 13.0)10.5 7.5(3.0, 15.3)
Week 120.6 0.3(-1.0, 2.0)-2.0 -0.1(-3.0, 0.5)-2.5 -1.0(-3.5, 0.0)-1.2 -0.5(-2.5, 0.0)-1.8 -1.0(-2.9, 0.0)
p value 0.001<0.0010.003<0.001
Week 24-0.3 0.0(-1.5, 1.0)-1.9 -0.5(-2.0, 0.0)-2.5 -1.0(-3.0, 0.0)-2.1 -0.8(-2.5, 0.5)-2.3 -0.8(-3.0, 0.0)
p value 0.043<0.0010.015<0.001
Bone erosion     
Baseline17.7 13.5(8.8, 19.0)21.0 15.8(10.8, 25.3)25.0 15.5(11.2, 27.0)21.3 13.3(10.0, 19.5)23.1 13.9(11.0, 22.8)
Week 120.2 0.0(0.0, 0.5)0.5 0.0(0.0, 0.5)-0.8 0.0(-0.5, 0.5)0.0 0.0(-0.1, 0.0)-0.4 0.0(-0.5, 0.5)
p value 0.6600.0360.0540.016
Week 24-0.2 0.0(0.0, 0.5)0.5 0.0(0.0, 0.5)-0.7 0.0(-0.6, 0.0)-0.2 0.0(-0.5, 0.0)-0.4 0.0(-0.5, 0.0)
p value 0.9730.0160.0280.010
* Given that several sites did not have the capability to obtain postgadolinium images, synovitis evaluations of the wrist and MCP joints were obtained in 71, 66, 67, and 68 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:
Ostergaard, Mikkel, Emery, Paul, Conaghan, Philip G., Fleischmann, Roy M., Xu, Weichun, Hsia, Elizabeth C., et al; Golimumab and Methotrexate Combination Therapy Significantly Improves Synovitis, Osteitis and Bone Erosion Compared to Methotrexate AloneA Magnetic Resonance Imaging Study of Methotrexate-Nave Rheumatoid Arthritis Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2264
DOI: 10.1002/art.30027

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