Baricitinib, a selective inhibitor of Janus kinase (JAK) 1 & 2, was approved in Europe for the treatment of rheumatoid arthritis (RA) in patients with an inadequate response to one or more DMARDs in February 2017, followed by FDA approval in May 2018 for patients in the USA with an inadequate response to tumor necrosis factor (TNF) inhibitor therapy.
The approval of baricinitib was based on the results of the “RA…” series of phase 3 clinical trials, which demonstrated the efficacy and safety profile of the JAK inhibitor compared with placebo or active comparators in patients with moderate-to-severe active RA.
Here, we provide a quick guide to the clinical trials of baricitinib in RA, including the four published phase 3 trials and earlier phase 2 studies. All of these trials are sponsored by Eli Lilly and Company or Incyte Corporation, two companies with a collaboration agreement for the development and marketing of baricitinib.
NCT00902486: Completed, not yet published
Phase 2 | |
Patient population: active RA and an inadequate response to any DMARD | Comparator treatment: placebo |
Although this dose-ranging study has not been published, the results were presented at the 2010 American College of Rheumatology meeting. The investigators reported that baricitinib (INCB028050) was well tolerated and gave rise to clinically meaningful responses over 12 weeks of treatment.
NCT01185353: Published
Phase 2b | |
Patient population: moderate-to-severe RA despite treatment with methotrexate | Comparator treatment: placebo |
The results of this phase 2b study, evaluating multiple doses of baricitinib and published in the Annals of the Rheumatic Diseases in 2014, showed that 76% of participants receiving baricitinib at a dose of 4 or 8 mg once daily experienced at least a 20% improvement in ACR criteria (ACR20) at week 12, compared with 41% of those in the placebo group, a significant difference.
Efficacy measures were similar for patients receiving 4 or 8 mg baricitinib, but fewer patients receiving the 2 mg dose achieved ACR responses and they had worse disease activity and lower rates of remission than those in the 4 mg and 8 mg groups. Therefore, 4 mg was selected as the optimal dose for evaluation in phase 3 studies.
Open-label follow-up results from this study were published in The Journal of Rheumatology in August 2017, and indicated that baricitinib continues to be well tolerated and efficacious for up to 2.5 years.
Related news story: Long-term results support baricitinib for the treatment of RA
NCT01469013: Published
Phase 2b | |
Patient population: Japanese patients with RA despite methotrexate therapy | Comparator treatment: placebo |
As reported in The Journal of Rheumatology in 2016, the results of this phase 2b trial showed that a significantly higher proportion of Japanese patients receiving treatment with baricitinib at a dose of 4 or 8 mg once daily achieved an ACR20 response at week 12 compared with those receiving placebo, at 77% versus 31%. The researchers observed improvements in disease activity, remission, and physical function from as early as week 2.
RA-BEACON: Published
Phase 3 | |
Patient population: moderate-to-severe RA and an inadequate response to TNF inhibitor or other biologic DMARD treatment | Comparator treatment: placebo |
The results of the RA-BEACON trial, reported in The New England Journal of Medicine in 2016, showed that a significantly higher percentage of patients receiving 4 mg baricitinib once daily versus placebo experienced an ACR20 response at week 12, at 55% versus 27%.
Participants in the 4 mg baricitinib group also had significantly greater improvements in the Health Assessment Questionnaire–Disability Index (HAQ-DI) score and Disease Activity Score at 28 joints based on C-reactive protein (DAS28-CRP) at week 12 compared with those in the placebo group, but there was no significant difference in the proportion of patients achieving a Simplified Disease Activity Index score of 3.3 points or lower between the two groups.
RA-BUILD: Published
Phase 3 | |
Patient population: moderate-to-severe RA; biologic-naïve and inadequate response to at least one conventional DMARD | Comparator treatment: placebo |
IN RA-BUILD, 62% of participants receiving 4 mg daily baricitinib achieved an ACR20 response at week 12, compared with 39% of patients receiving placebo, a significant difference. Patients treated with baricitinib also had higher scores on the HAQ-DI and other measures of disease activity, as well as greater improvements in joint pain and tiredness than those in the placebo group.
The results were published in the Annals of the Rheumatic Diseases in 2016.
RA-BEGIN: Published
Phase 3 | |
Patient population: active RA and no prior treatment with conventional or biologic DMARDs | Comparator treatment: methotrexate |
The results of the RA-BEGIN trial were published in Arthritis & Rheumatology in February 2017. They showed that a significantly greater proportion of participants receiving baricitinib monotherapy at a dose of 4 mg once daily had an ACR20 response at week 24 compared with those receiving methotrexate monotherapy, at 77% versus 62%.
Patients receiving combination therapy with baricitinib plus methotrexate had similar ACR20 response rates as those in the baricitinib monotherapy group.
RA-BEAM: Published
Phase 3 | |
Patient population: active RA and background therapy with methotrexate | Comparator treatment: placebo or adalimumab |
As reported in The New England Journal of Medicine in February 2017, patients receiving baricitinib had significantly higher ACR20 response rates at week 12 than those receiving placebo (70 vs 40 %).
Participants in the baricitinib group also experienced a significant reduction in radiographic progression of structural joint damage at week 24 compared with those in the placebo group. And 12-week ACR20 response rates were significantly higher among patients receiving baricitinib versus the active comparator adalimumab (70 vs 61%).
Related news story: Baricitinib shows promise in patients with RA
RA-BALANCE: Published
Phase 3 | |
Patient population: Patients from China, Argentina, and Brazil with moderate-to-severe RA and an inadequate response to methotrexate | Comparator treatment: placebo |
The main results from RA-BALANCE, published in Clinical and Experimental Rheumatology, demonstrated significantly higher ACR20 response rates at week 12 among participants treated with baricitinib versus placebo (58.6 vs 28.3%).
An analysis of Chinese participants, comprising 80% of the overall study population (n=290 patients), found similar results.
Related news story: RA-BALANCE: Further support for baricitinib in RA
RA-BEYOND: Ongoing
Phase 3 | |
Patient population: moderate-to-severe RA patients who have completed a previous baricitinib study | Comparator treatment: placebo |
This study will follow up patients who have completed one of the above studies, to determine baricitinib’s long-term efficacy and safety. Participants will be followed up for an additional 5 years in RA-BEYOND.
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