Baricitinib in moderate to severe rheumatoid arthritis: dose-dependent efficacy and safety in a randomized clinical trial in a developing country

Patients with rheumatoid arthritis (RA) who have an inadequate response or intolerance to methotrexate require effective and safe alternative therapies. Baricitinib, a Janus kinase inhibitor, has shown efficacy in RA, but dose-dependent outcomes in developing countries remain limited. To compare the efficacy and safety of baricitinib 2 mg versus 4 mg, both in combination with methotrexate, in patients with moderate-to-severe RA with an inadequate response to methotrexate. This was a 24-week, open-label, randomized controlled trial conducted in a developing country. Adult patients with moderate-to-severe RA and inadequate response or intolerance to methotrexate were randomly assigned (1:1) to receive either baricitinib 2 mg daily plus methotrexate 10 mg weekly or baricitinib 4 mg daily plus methotrexate 10 mg weekly. Primary outcome: proportion of patients achieving low disease activity (LDA) according to DAS28-CRP at week 24. Secondary endpoints included LDA by DAS28-ESR and Clinical Disease Activity Index (CDAI). The Simplified Disease Activity Index (SDAI), functional improvement assessed by the Bangla Health Assessment Questionnaire–Disability Index (B-HAQ), and changes in core set outcomes and acute-phase reactants. Safety outcomes were assessed throughout the study. Analyses were conducted on an intention-to-treat basis. A total of 94 patients were randomized, with 47 per treatment group. At week 24, LDA by DAS28-CRP was achieved by 38 patients (84.4%) in the baricitinib 4 mg group compared with 18 patients (45.0%) in the baricitinib 2 mg group (P = 0.01). Remission alone occurred in 16 patients (35.6%) receiving 4 mg and six patients (15.0%) receiving 2 mg (P = 0.03). LDA rates were also significantly higher in the 4 mg group, as assessed by CDAI (82.2% vs. 50.0%; P = 0.01) and SDAI (80.0% vs. 47.5%; P = 0.02). Except for erythrocyte sedimentation rate, all core set outcomes improved significantly more in the 4 mg group (P < 0.05). Functional status improved significantly within both groups (P < 0.05). Adverse events were generally mild to moderate. Herpes zoster occurred in two patients (4.5%) in the 4 mg group and one patient (2.5%) in the 2 mg group. No cases of tuberculosis, malignancy, venous thromboembolism, or death were observed. In patients with moderate-to-severe RA and an inadequate response to methotrexate, 4 mg baricitinib demonstrated superior efficacy compared with 2 mg baricitinib, with a comparable safety profile over 24 weeks. This study was registered with ClinicalTrials.gov (Identifier: NCT05660655, https://clinicaltrials.gov/ct2/show/NCT05660655) on 13 December 2022.