Personalized Arthritis Medication for Rheumatoid Arthritis

(SUPRA Trial)

Overseen By Marie Hudson, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Marie Hudson, MD

Must be taking: b/tsDMARDs

Disqualifiers: Active infection, Malignancy, Severe organ dysfunction, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to match individuals with rheumatoid arthritis to the treatment that works best for them, focusing on three types of medications: Anti-IL6 (such as Tocilizumab and Sarilumab), JAK inhibitors (such as tofacitinib and baricitinib), and TNF inhibitors. The goal is to determine which drug is most effective for each person, moving towards a personalized treatment plan. Suitable candidates for this trial have rheumatoid arthritis that hasn't responded well to standard medications and are ready to try a second or third line of treatment. As an unphased trial, this study offers an opportunity to explore personalized treatment options that might better manage the condition.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments under study—TNFi, JAKi, and Anti-IL6—have different safety profiles.

TNFi treatments, such as adalimumab and golimumab, have been used extensively. Studies suggest they can increase the risk of serious infections due to immune system suppression. However, they effectively manage rheumatoid arthritis.

JAK inhibitors, including tofacitinib and baricitinib, generally pose a low risk of side effects, particularly in the absence of existing heart problems. Some studies have raised concerns about infections and blood clots, but these risks are typically low.

Anti-IL6 treatments, like tocilizumab and sarilumab, have been researched for long-term safety. They are usually well-tolerated, though they carry a higher risk of serious infections. No major safety differences have been identified between these two drugs.

Overall, while some risks exist, these treatments have been widely used and are generally considered safe for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rheumatoid arthritis because they offer targeted approaches that differ from standard therapies like methotrexate or corticosteroids. Anti-IL6 treatments, such as tocilizumab and sarilumab, uniquely block the IL-6 receptor, reducing inflammation more specifically. JAK inhibitors like tofacitinib, baricitinib, and upadacitinib target JAK enzymes, which play a crucial role in the inflammatory process, offering a novel way to interfere with disease progression. Meanwhile, TNF inhibitors like etanercept, adalimumab, golimumab, and certolizumab pegol work by directly neutralizing TNF, a key inflammatory molecule. These targeted therapies could bring more customized and potentially more effective treatment options to patients.

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

This trial will compare the effectiveness of three treatments for rheumatoid arthritis: TNFi, JAKi, and Anti-IL6. Studies have shown that all three treatments are effective. Participants in the TNFi arm may receive treatments like adalimumab or etanercept, which work well, although effectiveness can vary based on factors such as rheumatoid factor levels. Those in the JAKi arm may receive inhibitors like tofacitinib or baricitinib, which have proven to be at least as effective as other advanced treatments, with clear improvements in symptoms. Participants in the Anti-IL6 arm may receive treatments such as tocilizumab or sarilumab, which have shown significant benefits in reducing disease activity and improving patient outcomes. Overall, these treatments have a strong record of effectiveness, but the best choice may depend on individual patient needs and responses. ^{6 7 8 9 10}

Who Is on the Research Team?

Marie Hudson, MD MPH

Principal Investigator

Sir Mortimer B. Davis - Jewish General Hospital

Are You a Good Fit for This Trial?

The SUPRA trial is for adults over 18 with Rheumatoid Arthritis who haven't improved after standard treatments. It's split into two parts: one for those needing a second-line treatment, and another for those where TNF inhibitors didn't work. Participants must be able to consent and fill out forms in English or French.

Inclusion Criteria

I have not responded to standard arthritis treatments and qualify for advanced therapy.

I have been diagnosed with rheumatoid arthritis according to the 2010 criteria.

Exclusion Criteria

I have another inflammatory condition like lupus that needs specific treatment.

I cannot take certain arthritis medications due to an active infection, current cancer, severe organ issues, history of blood clots (unless I'm on blood thinners), high risk of heart disease, or because I am pregnant/breastfeeding.

Unable to provide consent or complete forms (alone or with assistance) in English or French

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various treatments including TNFi, JAKi, and Anti-IL6 receptor monoclonal antibodies

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Feasibility Assessment

Assessment of feasibility outcomes such as patient adherence and recruitment rates

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-IL6
• JAKi
• TNFi

Trial Overview

This study tests different drugs (TNFi, JAKi, Anti-IL6) to find the best personalized treatment for Rheumatoid Arthritis patients. The goal is to match the right drug to each patient based on their specific needs at the correct time.

How Is the Trial Designed?

Group I: Sub-study 1 TNFi Active Control 1 Intervention

TNFi - any sub-cutaneous (sc) formulation, namely etanercept (receptor fusion protein), adalimumab (monoclonal antibody), golimumab (monoclonal antibody), or certolizumab (pegylated fragment of a monoclonal antibody)

Group II: Sub-study 2 JAKi Active Control 1 Intervention

JAKi - tofacitinib (JAK1/3 inhibitor), baricitinib (JAK 1/2 inhibitor) or upadacitinib (JAK1 inhibitor)

Group III: Sub-study 1 Anti-IL6 Active Control 1 Intervention

Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab

Group IV: Sub-study 2 Anti-IL6 Active Control 1 Intervention

Anti-IL6 receptor monoclonal antibodies - tocilizumab or sarilumab

Anti-IL6 is already approved in European Union, United States for the following indications:

Approved in European Union as Tocilizumab for:

• Rheumatoid arthritis
• Giant cell arteritis
• Polyarticular or systemic juvenile idiopathic arthritis
• Cytokine release syndrome

Approved in United States as Actemra for:

• Moderately to severely active rheumatoid arthritis
• Giant cell arteritis
• Polyarticular or systemic juvenile idiopathic arthritis
• Cytokine release syndrome

Approved in European Union as Sarilumab for:

• Moderately to severely active rheumatoid arthritis

Approved in United States as Kevzara for:

• Moderately to severely active rheumatoid arthritis

Who Is Running the Clinical Trial?

Marie Hudson, MD

Lead Sponsor

Trials

2

Recruited

90+

Lady Davis Institute

Collaborator

Trials

50

Recruited

6,600+

Montreal General Hospital

Collaborator

Trials

20

Recruited

10,400+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Tofacitinib is the first targeted synthetic DMARD approved for rheumatoid arthritis, functioning as a Janus kinase (JAK) inhibitor that reduces T-cell activation and inflammation, leading to decreased joint damage.

The safety and efficacy of tofacitinib have been evaluated in six phase 3 trials, demonstrating its effectiveness as a treatment option for RA, either alone or in combination with other non-biologic DMARDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis. Lundquist, LM., Cole, SW., Sikes, ML.[2022]

In a comparison of four Janus kinase inhibitors (tofacitinib, baricitinib, upadacitinib, and filgotinib) for treating rheumatoid arthritis in patients who did not respond adequately to other biologic treatments, no significant differences were found in efficacy based on Disease Activity Score and ACR20 response rates, indicating they may be similarly effective.

However, tofacitinib showed lower efficacy compared to upadacitinib, suggesting that while most JAK inhibitors are equivalent, tofacitinib may not be as effective as upadacitinib in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib. Vallez-Valero, L., Gasó-Gago, I., Marcos-Fendian, Á., et al.[2023]

In a Phase 3 trial involving 797 patients with rheumatoid arthritis who did not respond adequately to methotrexate, tofacitinib (5 or 10 mg twice daily) led to significant improvements in patient-reported outcomes (PROs) after 3 months, which were maintained over 24 months.

Patients receiving tofacitinib reported clinically meaningful enhancements in various aspects of health, including pain and quality of life, compared to those on placebo, with similar improvements observed in patients who switched from placebo to tofacitinib later in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: patient-reported outcomes from the 24-month Phase 3 ORAL Scan study. Strand, V., van der Heijde, D., Tanaka, Y., et al.[2022]

JAK inhibitors, such as tofacitinib and baricitinib, show superior efficacy compared to methotrexate in treating early rheumatoid arthritis (RA) patients who have not previously received treatment, and they are equally or more effective than adalimumab in certain cases.

While JAK inhibitors are effective, they carry a risk of serious infections similar to other advanced RA therapies, with a notably higher incidence of herpes zoster reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Janus kinase inhibitors in the treatment of rheumatoid arthritis: a systemic literature review. Jegatheeswaran, J., Turk, M., Pope, JE.[2020]

Tofacitinib and baricitinib are new oral drugs that effectively target the JAK-STAT signaling pathway to treat rheumatoid arthritis in patients who do not respond well to traditional treatments like methotrexate.

While these JAK inhibitors show promise in managing RA, clinicians face challenges in handling both serious and non-serious adverse events, necessitating careful consideration of patient age and comorbidities in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events, clinical considerations and management recommendations in rheumatoid arthritis patients treated with JAK inhibitors. Atzeni, F., Talotta, R., Nucera, V., et al.[2021]

In a study of 46,913 treatment courses for rheumatoid arthritis, the overall rate of treatment discontinuation due to adverse events was similar between Janus kinase inhibitors (JAKi) and tumor necrosis factor inhibitors (TNFi), suggesting comparable safety profiles.

However, specific JAKi like tofacitinib showed a higher rate of discontinuation compared to TNFi, indicating that the safety and tolerability of these treatments can vary significantly among different medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study). Aymon, R., Mongin, D., Bergstra, SA., et al.[2023]

In a 6-month study involving 399 patients with moderate-to-severe rheumatoid arthritis who did not respond adequately to TNF inhibitors, tofacitinib (5 mg and 10 mg) significantly improved symptoms and physical function compared to placebo, with ACR20 response rates of 41.7% and 48.1%, respectively.

Tofacitinib demonstrated a manageable safety profile, with common side effects including diarrhea and nasopharyngitis, making it a promising treatment option for patients with rheumatoid arthritis who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Burmester, GR., Blanco, R., Charles-Schoeman, C., et al.[2022]

Tofacitinib, an oral Janus kinase inhibitor, showed a therapy effectiveness rate of 15.4% in patients with rheumatoid arthritis previously treated with methotrexate, which is comparable to the effectiveness of non-TNF biologics (19.8%).

The study did not definitively establish whether tofacitinib was associated with a higher rate of serious infections requiring hospitalization compared to other treatments, indicating a need for further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study. Machado, MAÁ., Moura, CS., Guerra, SF., et al.[2019]

JAK inhibitors (jakinibs) like tofacitinib, upadacitinib, and others have shown significant efficacy in treating moderate-to-severe rheumatoid arthritis (RA) in patients who did not respond to conventional or biological treatments, with upadacitinib demonstrating the best overall results.

While most jakinibs are generally safe, tofacitinib was associated with 11 deaths in clinical studies, indicating a need for caution, especially in patients with severe liver and kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current jakinibs for the treatment of rheumatoid arthritis: a systematic review. Rocha, CM., Alves, AM., Bettanin, BF., et al.[2021]

Citations

1.

empr.com

empr.com/reports/tocilizumab-vs-sarilumab-mortality-cv-outcomes-compared-in-ra-patients/

Tocilizumab vs Sarilumab: Mortality, CV Outcomes ...

Treatment with sarilumab was associated with lower all-cause mortality compared with tocilizumab in adults with rheumatoid arthritis.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11557782/

Real-world Effectiveness of Sarilumab in RA

In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed ...

3.

arthritis-research.biomedcentral.com

arthritis-research.biomedcentral.com/articles/10.1186/s13075-025-03514-x

Comparative effectiveness of subcutaneous sarilumab 200 mg ...

SAR-SC 200 mg biweekly initiation was associated with a statistically significantly greater decrease in disease activity than TCZ-SC 162 mg biweekly in IL-6Ri- ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11891176/

Update on tocilizumab in rheumatoid arthritis: a narrative ...

This narrative review provides an update on TCZ's efficacy and safety based on data from randomized controlled trials (RCTs) and real-world evidence (RWE).

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0003496724427143

IL-6 receptor inhibition with tocilizumab improves treatment ...

Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30590833/

Safety and tolerability of subcutaneous sarilumab ...

This is the first analysis examining safety and tolerability of sarilumab and tocilizumab administered as single or multiple doses in patients with RA within ...

7.

frontiersin.org

frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1665293/full

Safety of Sarilumab in the treatment of rheumatoid arthritis

Sarilumab, a fully humanized IgG1 monoclonal antibody targeting the IL-6 receptor α, has shown efficacy in clinical trials but requires real-world safety ...

8.

actemrahcp.com

actemrahcp.com/ra/clinical-study-safety/clinical-study-safety.html

Rheumatoid Arthritis (RA) Clinical Trial Safety Side Effects

Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death.

9.

rheumatologyadvisor.com

rheumatologyadvisor.com/news/no-clinically-meaningful-safety-differences-between-sarilumab-tocilizumab-in-ra/

No Clinically Meaningful Safety Differences Between ...

The interleukin (IL)-6 inhibitors sarilumab and tocilizumab have shown no clinically relevant differences in safety and tolerability ...

10.

ard.bmj.com

ard.bmj.com/content/68/10/1580

Long-term safety and efficacy of tocilizumab, an anti-IL-6 ...

In this 5-year extension study, tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile.