RT Journal Article
SR Electronic
T1 MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 887
OP 895
DO 10.3899/jrheum.171469
VO 46
IS 8
A1 Charles Peterfy
A1 Julie DiCarlo
A1 Paul Emery
A1 Mark C. Genovese
A1 Edward C. Keystone
A1 Peter C. Taylor
A1 Doug E. Schlichting
A1 Scott D. Beattie
A1 Monica Luchi
A1 William Macias
YR 2019
UL http://www.jrheum.org/content/46/8/887.abstract
AB Objective. Magnetic resonance imaging (MRI) was used in a phase IIb study of baricitinib in patients with RA to support dose selection for the phase III program.Methods. Three hundred one patients with active RA who were taking 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. One hundred fifty-four patients with definitive radiographic erosion had MRI of the hand/wrist at baseline and at 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 + 3× synovitis score) and total joint damage (erosion + 2.5× cartilage loss score) scores were calculated. Treatment groups were compared using ANCOVA 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), respectively. 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. MRI findings in this subgroup of patients suggest suppression of synovitis, osteitis, and combined inflammation by baricitinib 4 and 8 mg. This corroborates previously demonstrated clinical efficacy of baricitinib and increases confidence that baricitinib 4 mg could reduce the radiographic progression in phase III studies. [Clinical trial registration number (www.ClinicalTrials.gov): NCT01185353]