Baricitinib 4 Mg Proves Effective for Reducing Joint Damage Progression for Patients with Rheumatoid Arthritis


Previously proven to be an effective and well-tolerated treatment for patients with RA, baricitinib can also help patients reduce joint damage progression and erosion.

A handful of studies have demonstrated that patients with moderate-to-severe rheumatoid arthritis (RA) can greatly reduce joint inflammation and damage by taking 2-4 mg of baricitinib daily, according to a comprehensive review of the literature published recently in Arthritis Research & Therapy.1 The medication has an osteoprotective effect that increases mineralization in bone-forming cells while not impacting the bone-resorbing cells.

Baricitinib, a selective Janus Kinase (JAK) inhibitor, has previously proven to be an effective and well-tolerated treatment for patients with RA who have experienced inadequate response to 1 or more TNF antagonist therapies. In this recent review of studies, patients taking baricitinib experienced a dose-dependent suppression of synovitis, osteitis, erosion, and cartilage loss versus placebo. This was confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM, and RA-BUILD) using MRIs to assess structural joint damage at various checkpoints.

Although 2 mg appears to slightly improve the symptoms of RA, the most effective dosage falls around the 4 mg mark, as the difference for 2 mg versus the placebo is not statistically significant in many cases. The phase 3 clinical studies confirm that baricitinib 4 mg greatly inhibits joint inflammation and radiographic joint damage progression.

For patients with RA, preventing damage to cartilage and bone is an important goal. Medicines that inhibit cytokine intracellular transduction pathways, like baricitinib, are currently being investigated as possible effective treatments of the disease. In all phase 3 studies, radiographic progression was measured using the van der Heijde modified total Sharp score (mTSS). Higher scores (ranging from 0 to 448) indicated greater joint damage.

During a preliminary MRI phase 2 study, the effects of baricitinib on joint damage progression were examined on patients with moderate-to-severe RA. Findings, which were scored for synovitis, osteitis, and bone erosion, demonstrated that individuals taking 4 mg of baricitinib had significant changes in joint inflammation, bone erosion and total joint damage versus the placebo.

In another early preclinical study, rats treated with baricitinib 10 mg/kg for 14 days were shown to have a major reduction in joint inflammation, ankle width, and bone resorption compared with vehicle-treated animals.

RA-BEGIN (NCT01711359) was a phase 3, randomized, double-blind, double-dummy, active comparator-controlled, 52-week study in 588 patients with early RA symptoms. Patients received methotrexate monotherapy once weekly, baricitinib monotherapy 4 mg once daily, or a combined treatment.

At week 24, baricitinib monotherapy or combination therapy proved superior to methotrexate monotherapy, according to American College of Rheumatology criteria (ACR20), which showed 77% improvement for baricitinib monotherapy, 78% for combined therapy, and 62% for methotrexate monotherapy. Additionally, the difference versus methotrexate was statistically significant for mTSS and erosion score for the combination therapy group as well as the proportion of patients who experienced no radiographic progression was also greater with baricitinib than with methotrexate monotherapy.

The second study,RA-BEAM (NCT01710358), was a phase 3, randomized, double-blind, placebo- and active-controlled, 52-week study in 1307 patents with moderate-to-severe active RA and an inadequate response to methotrexate. Patients received a placebo, baricitinib 4 mg once daily, or adalimumab 40 mg every other week. Once more, patients treated with baricitinib had a significantly greater ACR20 response than other treatment methods (70% vs 61%, respectively). By the final week, patients who had received baricitinib had smaller mean changes in mTSS, erosion score, joint space narrowing, and a greater proportion of patients who experienced no radiographic progression.

RA-BUILD (NCT01721057), was a phase 3, randomized, double-blind, placebo-controlled, 24-week study in 684 patients with moderate-to-severe active RA who were naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) and had shown an inadequate response or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients received either 2 or 4 mg of baricitinib or a placebo, in addition to any background therapies.

The authors of the study discovered that “the ACR20 response rate at week 12 was significantly greater with baricitinib 4 mg than with placebo (62% vs 39%). Exploratory analyses with respect to radiographic progression revealed a statistically significant reduction in mTSS and joint space narrowing from baseline to week 24 with both baricitinib doses compared with placebo. However, the reduction in joint erosion score versus placebo was significant only for baricitinib 4 mg. The proportion of patients with no radiographic progression was also significantly greater versus placebo for patients receiving baricitinib 4 mg.” Additionally, a recent analysis of 240 patients in this group showed that “treatment with baricitinib 4 mg once daily significantly reduced serum biomarkers of joint synovial inflammation and tissue destruction.”

Patients who completed baricitinib phase 2 and 3 clinical studies were eligible to enter the ongoing long-term extension study: RA-BEYOND (NCT01885078). At week 52, patients from RA-BEGIN who received methotrexate or baricitinib 4 mg plus methotrexate were switched to baricitinib 4 mg monotherapy.

The patients in all 3 groups (RA-BEGIN, RA-BEAM, and RA-BUILD) all showed significantly smaller mean changes in mTSS and erosion score at the 2-year mark. Investigators found that “the proportion of patients who experienced no radiographic progression was greater with baricitinib plus methotrexate and with baricitinib monotherapy than with methotrexate monotherapy, and the results were statistically significant for baricitinib plus methotrexate versus methotrexate monotherapy.” Furthermore, for the RA-BEAM and RA-BUILD groups, patients who had initially received baricitinib 4 mg had significantly smaller mean changes in joint space narrowing and experienced less radiographic progression versus the placebo. These studies show promising evidence that baricitinib is a powerfully effective tool for the continued treatment of patients with RA.


Emery P, Durez P, Hueber AJ, et al. Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis-a comprehensive review. Arthritis Res Ther. 2021;23(1):3. Published 2021 Jan 4. doi:10.1186/s13075-020-02379-6

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