Publications

MRI studies have shown that BARI reduces joint inflammation and damage in patients with moderate-to-severe active RA. This review summarises the effects of BARI on structural joint damage progression and the mechanisms underlying these effects, using MRI data from across the clinical trial program. Early preclinical animal models showed a significant reduction in joint inflammation, ankle width, and bone resorption. Efficacy and safety of BARI have been confirmed in an extensive programme, including MRI-based assessment of radiographic progression, joint erosion, and joint space narrowing. Preclinical studies have shown BARI has an osteoprotective effect, but no direct impact on bone-resorbing cells. Recent analysis of serum biomarkers in blood samples from patients in RA-BUILD showed BARI significantly reduced serum biomarkers of joint synovial inflammation and tissue destruction. The decrease in biomarker levels were associated with a decrease in disease activity composite scores, including the SDAI, CDAI, HAQ-DI and DAS28-ESR. ACR responses and improvements in disease activity at week 12 were significantly greater with BARI than with ADA. Patients receiving BARI also showed smaller mean changes in mTSS, erosion score and joint space narrowing than those on methotrexate monotherapy. Interestingly, those who achieved a sustained response were less likely to show radiographic progression at Week 52 than those who did not. A post hoc analysis based on clinical response suggested some characteristics were significantly associated with increased probability of structural progression, independent of treatment. These included female sex, lower BMI, smoking, higher hsCRP levels, and higher CDAI.