Use of Magnetic Resonance Imaging to Support Dose Selection in a Phase II Trial of Baricitinib Combined with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis. The Journal of rheumatology Peterfy, C., DiCarlo, J., Emery, P., Genovese, M. C., Keystone, E. C., Taylor, P. C., Schlichting, D. E., Beattie, S. D., Luchi, M., Macias, W. 2019


OBJECTIVE: Magnetic resonance imaging (MRI) was used in a Phase IIb study (NCT01185353) of baricitinib in patients with RA to support dose selection for the Phase III program.METHODS: 301 patients with active RA on stable methotrexate were randomized 2:1:1:1:1 to placebo or once-daily baricitinib (1-, 2-, 4-, or 8-mg) for up to 24 weeks. 154 patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and weeks 12 and 24. Two expert radiologists, blinded to treatment and visit order, scored images for synovitis, osteitis, bone erosion, and cartilage loss. Combined inflammation (osteitis + 3x synovitis score) and total joint damage (erosion + 2.5x cartilage loss score) scores were calculated. Treatment groups were compared using analysis of covariance adjusting for baseline scores.RESULTS: Mean changes from baseline to week 12 for synovitis were -0.10, -1.50, and -1.60 for patients treated with placebo, baricitinib 4-mg, and baricitinib 8-mg, respectively (P=0.003 vs placebo for baricitinib 4- and 8-mg); mean changes for osteitis were 0.00, -3.20, and -2.10 (P=0.001 vs placebo for baricitinib 4-mg and P=0.037 for 8-mg) and mean changes for bone erosion were 0.90, 0.10, and 0.40 (P=0.089 for 4-mg and P=0.275 for 8 mg), respectively in these treatment groups.CONCLUSION: Using MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4- and 8-mg, which corroborate previously demonstrated clinical efficacy of baricitinib and increase confidence that baricitinib 4-mg could positively effect reduction of the radiographic progression in Phase III studies.

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