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

Trial Summary

What is the purpose of this trial?

Rheumatoid arthritis is a disabling arthritis that affects young women disproportionately. Although the physicians have some excellent treatments, they do not know which treatment is best for which patient. The investigators want to find ways to identify the right drug for the right patient at the right time. This is what personalized medicine is all about.

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.

What data supports the effectiveness of the drugs used in the Personalized Arthritis Medication for Rheumatoid Arthritis trial?

Research shows that Janus kinase inhibitors (JAK inhibitors) like tofacitinib, baricitinib, upadacitinib, and filgotinib can be effective for patients with rheumatoid arthritis who haven't responded well to other treatments. These drugs have been shown to help reduce symptoms and improve patient-reported outcomes in clinical trials. ^{1 2 3 4 5}

Is the personalized arthritis medication generally safe for humans?

The safety of JAK inhibitors, a type of medication used for rheumatoid arthritis, has been studied, showing that they can cause side effects like serious infections and reactivation of herpes zoster (shingles). However, these side effects are similar to those seen with other advanced arthritis treatments. ^{2 3 4 6 7}

How is the drug tofacitinib unique for treating rheumatoid arthritis?

Tofacitinib is unique because it is an oral medication that targets specific enzymes (Janus kinase inhibitors) to reduce inflammation and joint damage in rheumatoid arthritis, unlike many other treatments that are injected or infused. ^{1 2 5 8 9}

Research Team

Marie Hudson, MD MPH

Principal Investigator

Sir Mortimer B. Davis - Jewish General Hospital

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. Germany 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. [2023]

3. England 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). [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Current jakinibs for the treatment of rheumatoid arthritis: a systematic review. [2021]

5. Italy 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of Janus kinase inhibitors in the treatment of rheumatoid arthritis: a systemic literature review. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Adverse events, clinical considerations and management recommendations in rheumatoid arthritis patients treated with JAK inhibitors. [2021]

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

Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study. [2019]