Inhibitin of structural joint damage progression in patients
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Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease.

In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2mg or 4mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage.

In patients naive to DMARDs (RA-BEGIN study), baricitinib 4mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate.

In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4?mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2mg once daily, but the effects of baricitinib 4mg were more robust. The positive effects of baricitinib 4mg on radiographic progression continued over 1 and 2years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo.

Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naive to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.

Source: https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02379-6
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