Baricitinib 4 mg once daily may reduce radiographic progression of active rheumatoid arthritis (RA), according to study results published in the Journal of Rheumatology.
Researchers conducted a substudy of participants in a phase 2 trial (NCT01185353) to evaluate patients with active RA despite treatment with methotrexate. Magnetic resonance imaging (MRI) data were used to support dose selection for the phase 3 trial.
In brief, patients were randomly assigned 2:1:1:1:1 to receive either placebo or baricitinib 1, 2, 4, or 8 mg once daily for 12 weeks. At 12 weeks, patients in the first 2 groups were randomly reassigned 1:1 to either baricitinib 2 mg twice daily or 4 mg once daily through week 24.
Patients participating in the MRI substudy underwent conventional radiography of hands, wrists, and feet. Persons with ≥1 definitive radiographic erosion underwent MRI of the most severely involved hand or wrist at baseline and weeks 12 and 24. Researchers scored images for synovitis, osteitis, bone erosion, and cartilage loss; combined inflammation and total joint damage scores were calculated.
In total, 154 patients met the entry criteria for the substudy. After randomization, 139 remained for the primary week 12 assessments. Among patients who participated in the substudy, 20% improvement in American College of Rheumatology response criteria were significantly higher in the baricitinib 4-mg and 8-mg groups at week 12 compared with placebo.
In addition, declines in the Disease Activity Score of 28 joints and level of high-sensitivity C-reactive protein; Health Assessment Questionaire-Disability Index (8 mg only); and swollen joint counts were significantly larger in the baricitinib 4-mg and 8-mg groups vs placebo at week 12. Treatment responses for the 4-mg and 8-mg groups were higher at week 24 and more efficacious vs the 2-mg dose.
At week 12, MRI measures of inflammation in the treatment group — including synovitis, osteitis, and combined inflammation scores — were significantly improved. Mean changes from baseline to week 12 in synovitis were −0.1 for the placebo group, −1.5 for the 4-mg group, and −1.6 for the 8-mg group. Mean changes for osteitis were 0, −3.2, and −2.1 and for bone erosion were 0.9, 0.1, and 0.4 in the placebo, 4-mg, and 8-mg groups, respectively.
Improvements continued through week 24, with decreases in both synovitis and combined inflammation scores appearing to be dose-dependent.
Compared with placebo, researchers noted a “statistically significant suppression of progression” at week 12 for bone erosion in the baricitinib 2-mg treatment arm, cartilage loss in the 4-mg treatment arm, and total joint damage in both arms. These measures remained stable at week 24.
Study limitations included the use of MRI assessments in only a small subgroup of patients and the assessment only of patients with evidence of erosive disease. In addition, statistical analyses were not adjusted for multiplicity, suggesting that some significant findings may be false positives.
“When reviewed in the context of the clinical findings, these data informed dose selection for the phase 3 program,” the researchers concluded. “The available imaging data from this… study increased confidence that the 4 mg baricitinib dose would be able to demonstrate a positive effect on reducing the rate of radiographic progression in phase 3 studies.”
This study was funded by Eli Lilly and Co and Incyte Corporation. Dr Di Carlo was an employee of Spires Science Inc., Dr Luchi was an employee of Incyte Corporation, and Dr Macias was an employee of Eli Lilly and Company at the time of this study.
Peterfy C, DiCarlo J, Emery P, et al. MRI and dose selection in a phase II trial of baricitinib with conventional synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis [published online January 15, 2019]. J Rheumatol. doi:10.3899/jrheum.171469