Advanced Therapeutics for Rheumatoid Arthritis

Overseen By Janet E Pope, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Biologics, JAK inhibitors

Disqualifiers: Active infection, Tuberculosis, Cancer, 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

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the retention rates of two advanced therapies, Tumour Necrosis Factor (TNF) and Janus kinase inhibitor (JAK) in the treatment of adults with Rheumatoid Arthritis (RA) over a two year period. It will also examine the ability to embed a clinical trial in a clinical situation using an electronic medical record (EMR).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must have failed treatments with methotrexate, hydroxychloroquine, sulfasalazine, and Leflunomide, which suggests that you may need to have tried these medications before joining the trial.

What data supports the idea that Advanced Therapeutics for Rheumatoid Arthritis is an effective treatment?

The available research shows that Advanced Therapeutics for Rheumatoid Arthritis, specifically etanercept, is effective in treating the condition. One study found that etanercept led to rapid improvement in symptoms over three months. Another study showed that adding etanercept to methotrexate, a common treatment, provided additional benefits for patients who still had active disease. Additionally, research on children with juvenile rheumatoid arthritis indicated that etanercept was effective for those who did not respond well to methotrexate. These studies suggest that etanercept can be a beneficial option for managing rheumatoid arthritis. ^{1 2 3 4 5}

What safety data is available for Etanercept in treating rheumatoid arthritis?

Etanercept, also known as Enbrel, has been shown to be safe in treating rheumatoid arthritis, with rapid, dose-dependent improvements observed over 3 months in a phase II study. Common minor side effects include injection site reactions and upper respiratory tract infections, which typically do not require discontinuation of the medication. Some patients have reported an urticaria-like rash. Overall, Etanercept has demonstrated significant improvements in rheumatoid arthritis symptoms in placebo-controlled trials. ^{1 4 6 7 8}

Is the drug Etanercept, Tofacitinib a promising treatment for rheumatoid arthritis?

Yes, Etanercept is a promising drug for treating rheumatoid arthritis. It has been shown to improve symptoms quickly and effectively when added to existing treatments. It works by targeting a specific protein involved in the inflammation process, helping to reduce the disease's activity. ^{1 2 3 4 9}

Research Team

Janet E Pope, MD MPH

Principal Investigator

Western University, Canada

Eligibility Criteria

This trial is for adults with active Rheumatoid Arthritis who have at least 5 swollen joints, are seropositive, show joint erosion, and haven't responded to standard treatments like methotrexate. They must be able to consent and attend follow-up visits. It's not for those with serious infections, tuberculosis, multiple sclerosis, current or past cancer (including lymphoma), or previous advanced therapy use.

Inclusion Criteria

Methotrexate, hydroxychloroquine, and sulfasalazine have not worked for me.

Leflunomide did not work for my condition.

I am 18 years old or older.

Exclusion Criteria

I am currently diagnosed with cancer.

I am not allergic or unable to take etanercept or tofacitinib.

I have had lymphoma at some point.

Treatment Details

Interventions

• Etanercept
• Tofacitinib

Trial Overview The study compares the retention rates of two RA treatments over two years: Etanercept (a TNF inhibitor) and Tofacitinib (a JAK inhibitor). It also assesses how well clinical trials can integrate into regular care using electronic medical records.

Participant Groups

Group I: etanercept Active Control 1 Intervention

etanercept 50 mg subcutaneously injected per week

Group II: tofacitinib Active Control 1 Intervention

tofacitinib 5 mg orally daily

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

Approved in United States as Enbrel for:

• Moderate to Severe Rheumatoid Arthritis
• Moderate to Severe Polyarticular Juvenile Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Moderate to Severe Plaque Psoriasis

Approved in European Union as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Approved in Canada as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Academic Medical Organization of Southwestern Ontario

Collaborator

Trials

17

Recruited

1,600+

Findings from Research

In a randomized, double-blind, placebo-controlled trial involving 234 patients with active rheumatoid arthritis, etanercept demonstrated significant improvements in disease activity over 6 months, with 59% of patients achieving a 20% improvement compared to only 11% in the placebo group.

Etanercept was well tolerated and showed a dose-dependent effect, with no dose-limiting toxic effects, confirming its safety and efficacy as a treatment for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Moreland, LW., Schiff, MH., Baumgartner, SW., et al.[2022]

In a 24-week study involving 89 patients with rheumatoid arthritis who were not responding adequately to methotrexate alone, the addition of etanercept significantly improved clinical outcomes, with 71% of patients achieving a 20% improvement in disease activity compared to only 27% in the placebo group.

The combination therapy was safe and well tolerated, with only mild injection-site reactions reported, indicating that etanercept can be a beneficial addition to methotrexate for patients with persistent disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. Weinblatt, ME., Kremer, JM., Bankhurst, AD., et al.[2022]

In a three-month trial involving 180 patients with refractory rheumatoid arthritis, the novel TNF antagonist TNFR:Fc significantly reduced disease activity, with 75% of patients receiving the highest dose (16 mg/m²) showing a 20% or greater improvement in symptoms compared to only 14% in the placebo group.

TNFR:Fc was found to be safe and well-tolerated, with only mild injection-site reactions and upper respiratory symptoms reported, and no serious side effects or antibodies against the treatment detected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. Moreland, LW., Baumgartner, SW., Schiff, MH., et al.[2022]

Etanercept is a fusion protein that acts as a soluble receptor for tumor necrosis factor (TNF), effectively used to treat various chronic inflammatory diseases in humans, such as rheumatoid arthritis and psoriasis.

To study its effects in mouse models, researchers developed a murine version of the soluble p75-TNF receptor, allowing for better understanding of its mechanism in conditions that mimic human granulomatous infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. Kim, HY., Renshaw-Gegg, LW., Balciunas, AM., et al.[2016]

In a study involving children aged 4 to 17 with polyarticular juvenile rheumatoid arthritis, 74% of patients responded positively to etanercept treatment after three months, indicating its efficacy in improving disease activity.

In a subsequent double-blind phase, patients receiving etanercept experienced significantly longer times to disease flare (over 116 days) compared to those on placebo (28 days), with no significant differences in adverse events, demonstrating its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. Lovell, DJ., Giannini, EH., Reiff, A., et al.[2022]

Etanercept has shown preliminary effectiveness in treating methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA), suggesting it could be a valuable option for patients who do not respond to standard treatments.

While most side effects of etanercept have been minor, two patients experienced a urticaria-like rash after injections, indicating that while generally safe, some individuals may have specific adverse reactions that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. Skyttä, E., Pohjankoski, H., Savolainen, A.[2017]

In a 24-week study involving 60 children with juvenile idiopathic arthritis (JIA), treatment with the etanercept biosimilar rhTNFR-Fc combined with methotrexate led to a significant reduction in disease activity, as measured by the cJADAS-10 score, which dropped from 14.66 to 2.4 (P < 0.01).

Approximately half of the patients achieved inactive disease status after 24 weeks, and improvements were also observed in symptoms like morning stiffness and joint effusions, indicating that rhTNFR-Fc is both effective and safe for treating JIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study. Xu, X., Liu, X., Zheng, W., et al.[2022]

Enbrel, a soluble tumor necrosis factor (TNF) receptor fusion protein, effectively inhibits TNF's biological effects and has been shown to significantly improve symptoms of rheumatoid arthritis in placebo-controlled trials.

Current clinical trials are evaluating the safety and efficacy of Enbrel in combination with methotrexate for patients with refractory rheumatoid arthritis, as well as comparing its effectiveness to methotrexate in early rheumatoid arthritis cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Soluble tumor necrosis factor receptor (p75) fusion protein (ENBREL) as a therapy for rheumatoid arthritis. Moreland, LW.[2019]

Tumor necrosis factor (TNF) is a key player in rheumatoid arthritis (RA), and recent advances have led to the development of targeted therapies like etanercept and infliximab, which directly inhibit TNF.

Both etanercept and infliximab have been shown to be effective and well tolerated in clinical trials for patients with refractory RA, as confirmed by placebo-controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor inhibitors: new options for treating rheumatoid arthritis. Moreland, LW.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Soluble tumor necrosis factor receptor (p75) fusion protein (ENBREL) as a therapy for rheumatoid arthritis. [2019]

9. Israel pubmed.ncbi.nlm.nih.gov

Tumor necrosis factor inhibitors: new options for treating rheumatoid arthritis. [2015]