TNFi Therapy Strategies for Juvenile Spondyloarthritis

(BACK-OFF JSpA Trial)

Recruiting at 31 trial locations

Overseen By Cora Sears, MPH

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Children's Hospital of Philadelphia

Must be taking: TNFi therapies

Disqualifiers: Inflammatory bowel disease, uncontrolled uveitis, psoriasis, others

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

Compensation: Varies

Number of Visits: 12

Duration: 12 months

198 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized pragmatic trial will generate knowledge about strategies used to de-escalate tumor necrosis factor inhibitor (TNFi) therapy in patients with juvenile spondyloarthritis with sustained inactive disease and are treated at one of the 29 participating pediatric healthcare systems. This open label study will be conducted in the setting of routine clinical care and will compare the risk and timing of flare (Aim 1) and patients' lived experiences (Aim 2) across three arms.

Will I have to stop taking my current medications?

The trial focuses on de-escalating (reducing) TNFi therapy, so you will not have to stop taking your current TNFi medication completely, but you will need to be willing to reduce it.

Is TNFi therapy safe for humans?

Etanercept, a TNFi therapy, has been shown to be generally safe in humans for conditions like rheumatoid arthritis and juvenile idiopathic arthritis. Common side effects include minor injection site reactions and upper respiratory infections, but caution is advised due to potential risks like re-activating tuberculosis and concerns about lymphoma. ^{1 2 3 4 5}

How is the drug etanercept unique in treating juvenile spondyloarthritis?

Etanercept is a tumor necrosis factor inhibitor (TNFi) that is used to treat juvenile spondyloarthritis by reducing inflammation and slowing disease progression. It is unique because it is specifically designed to block the action of a protein called TNF, which is involved in systemic inflammation, and it has been shown to improve physical functionality and reduce disease activity in patients who do not respond well to other treatments like NSAIDs. ^{3 6 7 8 9}

What data supports the effectiveness of this drug for juvenile spondyloarthritis?

Research shows that etanercept, a drug similar to the one used in this trial, has been effective in treating conditions like juvenile rheumatoid arthritis and enthesitis-related arthritis, which are related to juvenile spondyloarthritis. This suggests it may also be effective for juvenile spondyloarthritis. ^{1 2 3 10 11}

Are You a Good Fit for This Trial?

This trial is for kids and young adults aged 8 to 21 with juvenile spondyloarthritis, who have been symptom-free for at least six months while on standard TNFi therapy. They must meet specific criteria including arthritis or enthesitis, and not have certain conditions like inflammatory bowel disease or psoriasis requiring more than topical treatment.

Inclusion Criteria

I am between 8 and 21 years old.

My arthritis symptoms started before I was 16.

I have arthritis or enthesitis and at least two other related symptoms.

Exclusion Criteria

My psoriasis started before my TNF inhibitor treatment.

I have a history of inflammatory bowel disease.

My eye inflammation wasn't controlled with local treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of three treatment arms: continued fixed standard dosing, fixed longer dosing intervals, or stopping TNFi, for 12 months

12 months

4 visits (in-person)

Follow-up

Participants are monitored for long-term outcomes after the intervention period

24 months

8 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Standard TNFi Therapy
• TNFi fixed longer dosing intervals
• TNFi treatment

Trial Overview The study tests three approaches in patients with inactive juvenile spondyloarthritis: continuing standard TNFi therapy, stopping TNFi treatment altogether, or extending the time between doses of TNFi. It aims to see which strategy best balances flare frequency with quality of life.

How Is the Trial Designed?

Group I: TNFi fixed longer dosing intervals Experimental Treatment 1 Intervention

Fixed longer dosing intervals of TNFi (i.e., increased time between doses)

Group II: TNFi Therapy Withdrawal Experimental Treatment 1 Intervention

Stop TNFi treatment

Group III: TNFi Standard Therapy Active Control 1 Intervention

Continue fixed standard treatment (i.e., no change from current therapy)

Standard TNFi Therapy is already approved in United States, European Union 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

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

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]

In an open-label pilot trial involving 8 children with enthesitis-related arthritis (ERA), treatment with the TNF fusion protein etanercept led to significant improvements in active joint count, hemoglobin levels, and erythrocyte sedimentation rate (ESR) within just 2 months.

All patients tolerated etanercept well with no reported side effects, and the benefits were sustained over the entire 2-year study period, indicating its potential as an effective long-term treatment for ERA refractory to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. Henrickson, M., Reiff, A.[2015]

In a study of 40 patients with active ankylosing spondylitis, etanercept treatment led to significant improvements in disease symptoms, with 80% of patients responding positively compared to only 30% in the placebo group after four months.

Etanercept was well tolerated, showing no significant difference in adverse events compared to the placebo, indicating it is a safe option for managing ankylosing spondylitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. Gorman, JD., Sack, KE., Davis, JC.[2015]

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 study of 68 patients with active ankylosing spondylitis, treatment with rh TNFR:Fc significantly improved symptoms, with 85% of patients achieving at least a 20% improvement (ASAS20) by week 24.

While rh TNFR:Fc showed rapid symptom relief, radiological improvements in joint structure were not significant until week 24, indicating that while symptoms improve quickly, structural changes may take longer to manifest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical evaluation and radiological observation of recombinant human tumor necrosis factor receptor-Fc fusion protein in treatment of active ankylosing spondylitis]. Pan, XY., Li, J., Pang, J., et al.[2015]

Etanercept is an effective and safe treatment for rheumatoid arthritis (RA), significantly reducing disease activity and preventing joint damage, and can be used alone or with methotrexate for enhanced effectiveness.

While generally safe, etanercept requires caution due to potential risks such as re-activating tuberculosis and concerns about lymphoma, and it is recommended for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. Scott, DL.[2015]

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]

Juvenile spondyloarthritis, a type of juvenile idiopathic arthritis, is closely linked to HLA B-27 positivity and can lead to serious complications like ankylosing spondylitis, making effective treatment crucial.

Current severe disease management primarily uses tumor necrosis factor inhibitors (TNFi), but there are additional treatment options available for adults, such as IL-17 and IL-23 blockers, which may not yet be fully explored in pediatric guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Juvenile Spondyloarthritis: Where We Stand. Bridges, JM., Stoll, ML.[2021]

In a study of 86 patients with juvenile spondyloarthropathy (JSpA), the main reason for starting tumor necrosis factor inhibitors (TNFi) was active disease observed during physical exams, affecting 61% of patients.

After 6 months of TNFi therapy, patients showed significant improvements, including a reduction in active joints and enthesitis, as well as decreased pain; however, 54% still had active disease after 12 months, indicating that while TNFi can help, it may not fully control the disease in all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of Tumor Necrosis Factor Inhibitor Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomess. Oliver, M., Simard, JF., Lee, T., et al.[2022]

In a study of 20 patients with juvenile spondyloarthropathies who did not respond to NSAIDs, TNFalpha antagonist therapy showed significant clinical and laboratory improvements within 3 months, with 59% achieving remission.

The treatment was generally safe, with only two serious adverse events reported, and benefits were sustained for up to a year, although discontinuation often led to relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of TNFalpha antagonist therapy in patients with juvenile spondyloarthropathies. Sulpice, M., Deslandre, CJ., Quartier, P.[2020]

In a study of 804 patients with ankylosing spondylitis, those using tumor necrosis factor inhibitors (TNFis) showed significantly greater reductions in disease activity and improvements in physical functionality compared to non-users over 12 months.

Despite some patients discontinuing TNFis, the treatment still appeared to help maintain spinal mobility, suggesting that TNFis can effectively manage symptoms and potentially slow the progression of mobility issues in ankylosing spondylitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Subcutaneous Tumor Necrosis Factor Inhibitors in Patients With Ankylosing Spondylitis: A Real-World Prospective Observational Cohort Study in China. Ji, X., Wang, Y., Hu, Z., et al.[2020]

Citations

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

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

2. Canada pubmed.ncbi.nlm.nih.gov

Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. [2015]

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

Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. [2015]

4. 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]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical evaluation and radiological observation of recombinant human tumor necrosis factor receptor-Fc fusion protein in treatment of active ankylosing spondylitis]. [2015]

6. India pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. [2015]

7. Italy pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of Juvenile Spondyloarthritis: Where We Stand. [2021]

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

Determinants of Tumor Necrosis Factor Inhibitor Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomess. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Efficacy and safety of TNFalpha antagonist therapy in patients with juvenile spondyloarthropathies. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Subcutaneous Tumor Necrosis Factor Inhibitors in Patients With Ankylosing Spondylitis: A Real-World Prospective Observational Cohort Study in China. [2020]