Baricitinib for Rheumatoid Arthritis

(RA-BRANCH Trial)

No longer recruiting at 175 trial locations

Overseen By Alan Kivitz

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Eli Lilly and Company

Must be taking: DMARDs

Must not be taking: JAK inhibitors

Disqualifiers: Cancer, Active tuberculosis, Serious infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety of the drug baricitinib compared to TNF inhibitors for individuals with rheumatoid arthritis (RA), with a particular focus on blood clots. It includes three groups: one receiving a high dose of baricitinib, another a low dose, and a third taking TNF inhibitors such as adalimumab or etanercept. The trial seeks participants with RA who have experienced issues like previous blood clots or a high BMI (a measure of body fat). Participants should also have had limited success with other RA treatments. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you must not have used a Janus kinase (JAK) inhibitor before or more than one TNF inhibitor that was stopped due to lack of effectiveness or intolerance.

What is the safety track record for these treatments?

Research has shown that baricitinib is generally safe, with studies finding its safety comparable to other rheumatoid arthritis (RA) treatments. Patients have taken baricitinib for up to 9.3 years, and it is usually well-tolerated. However, like other RA treatments, it carries a risk of infections, especially since RA patients are already more susceptible.

Similarly, TNF inhibitors such as adalimumab and etanercept are widely used for RA and have well-established safety records. They target specific proteins in the immune system to reduce inflammation.

Both baricitinib and TNF inhibitors have received approval for RA, indicating their safety for this condition. This study aims to closely compare these treatments concerning rare blood clot events. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for rheumatoid arthritis, which typically include TNF inhibitors like adalimumab or etanercept, Baricitinib offers a different approach. It works by inhibiting Janus kinase (JAK) enzymes, which play a crucial role in the inflammatory process. This new mechanism of action can potentially provide relief for patients who don't respond well to TNF inhibitors. Additionally, Baricitinib is administered orally, which may be more convenient compared to the subcutaneous injections required for TNF inhibitors. Researchers are excited about Baricitinib because it provides a novel pathway for addressing inflammation in rheumatoid arthritis, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for rheumatoid arthritis?

Research has shown that baricitinib effectively treats rheumatoid arthritis (RA). Studies have found that both 4 mg and 2 mg doses of baricitinib can control the disease and even lead to remission for up to 6.5 years. In this trial, participants will receive either a high or low dose of baricitinib. After 12 weeks, 20% of patients taking baricitinib with other RA medications showed significant improvement, compared to only 8% who took a placebo. Additionally, about 80% of patients on the higher dose and 70% on the lower dose maintained their improvement over time. This treatment has already proven effective for RA, which is why researchers are comparing it to TNF inhibitors in this study. ^{3 4 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for people over 60 with rheumatoid arthritis who've had a blood clot (VTE) and are overweight (BMI ≥30 kg/m²). It's not for those with cancer, previous JAK inhibitor use, or more than one TNF inhibitor treatment. Participants should have tried at least one RA medication without success.

Inclusion Criteria

You have a BMI of 30 or higher.

I am 60 years old or older.

Documented evidence of a VTE prior to this study

Exclusion Criteria

I have not responded well or am intolerant to at least one arthritis medication.

I have not responded well or am intolerant to at least one arthritis medication.

I do not have cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either baricitinib or TNF inhibitors to compare safety with respect to venous thromboembolic events

Approximately 5.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib
• TNF Inhibitor

Trial Overview The study compares the safety of Baricitinib, a drug targeting immune response, to TNF inhibitors in preventing blood clots in patients with rheumatoid arthritis. The goal is to see which treatment has fewer risks associated with VTEs.

How Is the Trial Designed?

Group I: Baricitinib Low Dose Experimental Treatment 1 Intervention

Baricitinib administered orally.

Group II: Baricitinib High Dose Experimental Treatment 1 Intervention

Baricitinib administered orally.

Group III: TNF Inhibitor Active Control 1 Intervention

Adalimumab or etanercept administered subcutaneously (SC) per standard of care.

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

Baricitinib, a selective JAK1/JAK2 inhibitor, has demonstrated significant clinical efficacy in patients with rheumatoid arthritis (RA) who did not respond adequately to conventional and biological DMARDs, showing improvements in radiographic joint damage in pivotal phase III trials.

The drug was well tolerated with no unexpected safety issues reported, and a long-term phase III study is currently assessing its safety and efficacy over four years, indicating ongoing commitment to understanding its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib: JAK inhibition for rheumatoid arthritis. Gras, J.[2021]

Baricitinib is an effective treatment for moderately to severely active rheumatoid arthritis (RA), showing significant benefits over placebo, methotrexate, and adalimumab in improving symptoms and quality of life, as demonstrated in Phase III randomized controlled trials.

While baricitinib has an acceptable safety profile, it is associated with some rare but serious adverse events, including infections and malignancies, making monitoring necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New alternative in the treatment of rheumatoid arthritis: clinical utility of baricitinib. Kawalec, P., Śladowska, K., Malinowska-Lipień, I., et al.[2020]

Baricitinib demonstrated a consistent safety profile over 128 weeks in patients with rheumatoid arthritis, with treatment-emergent adverse events occurring in 63% of patients on 4 mg and 67% on 8 mg, and no unexpected late safety signals identified.

Clinical improvements in disease symptoms were maintained beyond the initial 24-week blinded period, with similar or increased rates of disease improvement observed at weeks 76 and 128, indicating the long-term efficacy of baricitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis. Keystone, EC., Genovese, MC., Schlichting, DE., et al.[2021]

Baricitinib has shown real-world effectiveness in treating moderate-to-severe rheumatoid arthritis, with 8.7-60% of patients achieving remission within 12 weeks and 20.2-81.6% reaching low disease activity by 24 weeks, indicating its efficacy across various patient backgrounds.

The safety profile of baricitinib remains consistent with previous clinical studies, and it demonstrates high drug persistence rates comparable to anti-tumor necrosis factor drugs, suggesting it is a reliable treatment option for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis. Hernández-Cruz, B., Kiltz, U., Avouac, J., et al.[2023]

Baricitinib is an effective oral treatment for rheumatoid arthritis (RA), particularly in patients who have not responded to other therapies, showing efficacy in four clinical trials and delaying radiographic progression of the disease.

While the 4 mg dose of baricitinib demonstrated greater efficacy, only the 2 mg dose is FDA approved due to safety concerns, particularly the risk of thromboembolism, highlighting the importance of weighing safety and effectiveness when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis. Mogul, A., Corsi, K., McAuliffe, L.[2021]

In a double-blind phase III study involving 527 patients with moderately to severely active rheumatoid arthritis who had not responded to previous treatments, baricitinib significantly improved patient-reported outcomes (PROs) compared to placebo over 24 weeks.

Patients receiving the higher dose of baricitinib (4 mg) experienced more rapid and greater improvements in physical functioning, fatigue, pain, and morning joint stiffness, indicating its efficacy as a treatment option for those with treatment-refractory rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Smolen, JS., Kremer, JM., Gaich, CL., et al.[2021]

In a two-year study of 44 patients with rheumatoid arthritis, both baricitinib and tofacitinib were found to be effective in reducing disease activity, with baricitinib showing slightly greater reductions in the DAS28 scale and pain levels over 12 months.

Both medications had similar safety profiles, with low rates of adverse reactions (10% for baricitinib and 12.5% for tofacitinib) and comparable treatment discontinuation rates due to loss of effectiveness, indicating they are both viable options for managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib and tofacitinib in patients with rheumatoid arthritis: results of regular clinical practice. González-Freire, L., Giménez-Candela, RM., Castro-Luaces, S., et al.[2021]

Baricitinib is an effective oral treatment for moderate to severe rheumatoid arthritis (RA), showing significant improvements in symptoms, disease activity, and physical function in patients who did not respond well to other DMARDs, based on pivotal trials involving multiple countries.

The treatment was generally well tolerated over a duration of up to 5.5 years, with common side effects including upper respiratory infections and increased LDL cholesterol, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib: A Review in Rheumatoid Arthritis. Al-Salama, ZT., Scott, LJ.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38258434/

Efficacy of baricitinib in patients with moderate-to-severe ... Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11443035/

Efficacy of baricitinib in patients with moderate-to-severe ... Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02265705

NCT02265705 | A Study of Baricitinib (LY3009104) in ... The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as baricitinib in participants with moderately to ...

4. olumiant.lilly.com olumiant.lilly.com/hcp/rheumatoid-arthritis

Rheumatoid Arthritis | HCP - Olumiant® (baricitinib) - Eli Lilly At week 12, 20% of patients taking Olumiant 2 mg/day plus cDMARDs achieved an ACR50 response compared to 8% of patients taking placebo plus cDMARDs, with a p- ...

5. jrheum.org jrheum.org/content/52/4/316

Baricitinib Dose Reduction in Patients With Rheumatoid ... Published preliminary data reported approximately 80% of patients in the baricitinib 4-mg group and 70% of patients in the 2-mg group sustained ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9443639/

A Review of Safety Outcomes from Clinical Trials ... Patients with RA, AD and SLE have an increased risk for infections compared with those without the disease or the general population, with the ...

7. ard.bmj.com ard.bmj.com/content/81/3/335

Safety of baricitinib for the treatment of rheumatoid arthritis ... The results suggest that baricitinib has a consistent safety profile as demonstrated in previous reports and is in line with other JAK inhibitors and biologic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11653574/

Efficacy and safety of baricitinib in rheumatoid arthritis ... Baricitinib 2 mg in RA patients with moderate renal dysfunction showed comparable efficacy and retention rate to 4 mg in patients with normal/mild renal ...