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12-09-2017 | Rheumatoid arthritis | Feature | Article

At a glance: Trials evaluating baricitinib in RA

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 disease-modifying antirheumatic drugs (DMARDs) in February 2017.

This approval was based on the results of the “RA…” series of phase III clinical trials, which demonstrated the efficacy and safety profile of baricitinib compared with placebo or active comparators in patients with moderate-to-severe active RA. Baricitinib is not currently approved for use in the USA.

Here, we provide a quick guide to the clinical trials of baricitinib in RA, including the four published phase III trials and earlier phase II 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 II

Patient population: active RA and an inadequate response to any DMARD

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT00902486

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 IIb

Patient population: moderate-to-severe RA despite treatment with methotrexate

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT01185353

The results of this phase IIb 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 III 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 IIb

Patient population: Japanese patients with RA despite methotrexate therapy

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT01469013

As reported in The Journal of Rheumatology in 2016, the results of this phase IIb 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 III

Patient population: moderate-to-severe RA and an inadequate response to TNF inhibitor or other biologic DMARD treatment

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT01721044

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 III

Patient population: moderate-to-severe RA; biologic-naïve and inadequate response to at least one conventional DMARD

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT0172105

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 III

Patient population: active RA and no prior treatment with conventional or biologic DMARDs

Comparator treatment: methotrexate

https://clinicaltrials.gov/ct2/show/NCT01711359

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 III

Patient population: active RA and background therapy with methotrexate

Comparator treatment: placebo or adalimumab

https://clinicaltrials.gov/ct2/show/NCT01710358

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

 

NCT02265705: Ongoing

Phase III

Patient population: moderate-to-severe RA and an inadequate response to methotrexate

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT02265705

This 52-week trial is investigating the efficacy and safety of baricitinib 4 mg once daily versus placebo, with a primary endpoint of ACR20 response at week 12. Participants will continue to receive background methotrexate treatment throughout the study.

 

RA-BEYOND: Currently recruiting

Phase III

Patient population: moderate-to-severe RA patients who have completed a previous baricitinib study

Comparator treatment: placebo

https://clinicaltrials.gov/ct2/show/NCT01885078

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.

By Claire Barnard

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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