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

Duration: 24 months

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two advanced treatments for Rheumatoid Arthritis (RA), Etanercept (a TNF inhibitor) and Tofacitinib (a JAK inhibitor), over two years. Researchers aim to determine patient adherence to these treatments and how electronic medical records can facilitate trial management in a real-world setting. It suits individuals with active RA who have not found relief with other medications like methotrexate or hydroxychloroquine and have at least five swollen joints. As a Phase 4 trial, this research seeks to understand how these FDA-approved and effective treatments can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that etanercept is generally safe and effective for treating rheumatoid arthritis (RA). In past studies, about 4% of patients experienced serious side effects, though none were fatal, and about 3% discontinued use due to side effects. Long-term research indicates that etanercept remains safe for extended use.

Tofacitinib has also undergone safety studies for RA. It is considered safe when patients are carefully selected. Common side effects include colds, headaches, and diarrhea. However, concerns exist about an increased risk of heart problems and cancer, making it crucial to discuss health conditions with a doctor before starting treatment.

Both treatments have been tested in various settings and are generally well-tolerated, but individual experiences can vary. Consulting healthcare providers is essential to determine the best option for individual health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for rheumatoid arthritis because they offer unique approaches to managing the condition. Etanercept works by targeting and inhibiting tumor necrosis factor (TNF), a substance in the body that causes inflammation and is a key player in rheumatoid arthritis progression. This is different from many standard treatments that might not specifically target TNF. On the other hand, Tofacitinib is distinctive because it is taken orally and works by inhibiting Janus kinase (JAK) pathways, which play a crucial role in the inflammatory process. These innovative methods of action give hope for more effective and potentially faster relief for patients compared to traditional treatments.

What is the effectiveness track record for Etanercept and Tofacitinib in treating Rheumatoid Arthritis?

Research has shown that both etanercept and tofacitinib effectively treat rheumatoid arthritis (RA). In this trial, participants will receive either etanercept or tofacitinib. One study found that 49.8% of patients taking etanercept with methotrexate experienced significant symptom improvement, reaching remission. Another study showed that many patients did not experience worsening of joint damage while using etanercept. For tofacitinib, more than half of the patients felt better within three months of starting treatment. Additionally, 31.9% of patients had low disease activity after a year on tofacitinib. These results highlight the potential of both treatments to relieve RA symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Janet E Pope, MD MPH

Principal Investigator

Western University, Canada

Are You a Good Fit for This Trial?

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 have active rheumatoid arthritis with 5 or more swollen joints.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either etanercept or tofacitinib for the treatment of Rheumatoid Arthritis

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8964852/

Effectiveness of Etanercept in Rheumatoid Arthritis In this non-interventional study, 24% and 39% of patients with RA treated with ETN as part of routine care in Germany achieved remission and LDA ...

2. enbrelpro.com enbrelpro.com/efficacy/rheumatoid-arthritis

Rheumatoid Arthritis (RA) Efficacy Primary endpoint results · DAS 28 remission (DAS 28 <2.6) was achieved by 49.8% of patients with ENBREL + MTX vs 27.8% with MTX at Year 1 (P<0.001) · Change from ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9575986/

Real-world effectiveness and persistence of reference ... Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting.

4. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr.25092

Effectiveness and Persistence in SB4‐ and Reference ... Outcomes for disease status/drug persistence at week 52 were similar between patients with RA treated with etanercept or SB4. INTRODUCTION. The ...

5. amgen.com amgen.com/newsroom/press-releases/2003/10/new-data-show-many-rheumatoid-arthritis-patients-treated-with-enbrel-plus-methotrexate-have-experienced-clinical-remission-and-most-had-no-progression-of-joint-damage

New Data Show Many Rheumatoid Arthritis Patients ... 80 percent of combination-treated patients experienced no progression of joint damage and a majority (51 percent) of patients reported significant improvement ...

6. enbrelpro.com enbrelpro.com/safety/rheumatoid-arthritis

Rheumatoid Arthritis (RA) Safety | Enbrel® (etanercept) Safety Data ; Serious adverse events, 4 (4.0) ; Adverse events leading to discontinuation of investigational product, 3 (3.0) ; Fatal adverse events, 0 (0.0) ...

7. enbrel.com enbrel.com/rheumatoid-arthritis

Rheumatoid Arthritis Treatment | ENBREL® (etanercept) Learn about ENBREL® (etanercept) for moderate to severe rheumatoid arthritis (RA). See Full Prescribing & Safety Info.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/103795s5556lbl.pdf

ENBREL (etanercept) - accessdata.fda.gov In controlled portions of trials in RA, PsA, AS and PsO, the rates of serious infection were similar (0.8% in placebo,. 3.6% in MTX, and 1.4% in Enbrel/Enbrel + ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1798057/

Long term safety of etanercept in elderly subjects with ... Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly.

10. amgen.com amgen.com/newsroom/press-releases/2007/06/enbrel-safety-data-for-up-to-eight-years-in-patients-with-juvenile-rheumatoid-arthritis-being-presented-at-eular

ENBREL Safety Data for up to Eight Years in Patients with ... -- ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in patients who have ...