Background: Baricitinib is effective in the treatment of rheumatoid arthritis (RA) patients who are not responding to the optimum dose of methotrexate, though safety is a concern with the 4 mg dose.

Objectives: To assess the efficacy and safety of baricitinib in different doses for the treatment of patients with moderate to severe rheumatoid arthritis (RA) despite adequate treatment with methotrexate.

Methods: In this open-label, randomized controlled, 24-week trial, a total of 94 patients who had an inadequate response or intolerance to methotrexate were randomly assigned to baricitinib 2 mg daily plus methotrexate 10 mg weekly (47 patients) and baricitinib 4 mg daily plus methotrexate 10 mg weekly (47 patients). The primary efficacy endpoint was the achievement of low disease activity (LDA) plus remission measured with Disease Activity Score-28 by C-reactive protein (DAS28-CRP). The secondary efficacy endpoints were the achievement of LDA plus remission by DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Bangla version of the Health Assessment Questionnaire-Disability Index (B-HAQ) response and the mean changes of the core set of outcomes from baseline at 24 weeks were analyzed. Changes in acute phase reactants and composite measures within the groups from baseline to 24 weeks were also analyzed.

Results: At 24 weeks, LDA plus remission in DAS28-CRP was attained in 38 (84.4%) and 18 (45.0%) patients in the baricitinib 4 mg and 2 mg groups, respectively (P=0.01). In the 4 mg and 2 mg groups, this was achieved in 16 (35.6%) and 6 (15%) patients, respectively (P= 0.03). In CDAI, LDA plus remission was achieved in 37 (82.2%) patients in the 4 mg and 20 (50.0%) patients in the 2 mg group (P=0.01), while in SDAI, it was achieved in 36 (80.0%) patients in the 4 mg and 19 (47.5%) patients in the 2 mg group (P=0.02). Except for ESR, the core set of outcomes also improved significantly in the baricitinib 4 mg group than in the 2 mg group (P<0.05). The functional status (measured by B-HAQ) significantly decreased within the groups (P<0.05). Two patients (4.5%) in the 4 mg group and 1 (2.5%) in the 2 mg group developed herpes zoster. Five (12.5%) patients in 2 mg group and 11 (24.4%) in 4 mg group developed skin eruptions/itching. None of the study subjects developed tuberculosis, malignancy, or venous thromboembolism. There were no reported cases of death. Elevated liver enzyme developed in 4 (8.9%) patients in the 4 mg group and none in the baricitinib 2 mg group. Renal impairment was seen in 3 (7.5%) patients in 2 mg and 1 (2.2%) in the 4 mg group.

Conclusion: Baricitinib 4 mg is more effective than baricitinib 2 mg in patients with RA who had an inadequate response to methotrexate. In terms of safety, there were no significant difference between the group.

Trial registration number NCT05660655.

REFERENCES: NIL. Acknowledgements: NIL.

Disclosure of Interests: None declared.