Adalimumab for Arthritis

Overseen By Tom Appleton, MD, PhD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tom Appleton

Must not be taking: Chloroquine, Sulfasalazine, Azathioprine, others

Disqualifiers: Rheumatoid arthritis, Lupus, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications like Chloroquine, Sulfasalazine, Azathioprine, 6-MP, and Leflunomide. If you are on these, you would need to discontinue them to participate.

What data supports the effectiveness of the drug Adalimumab for treating arthritis?

Research shows that Adalimumab is effective in treating psoriatic arthritis and rheumatoid arthritis, improving symptoms and quality of life for patients who did not respond well to other treatments. It works by targeting a specific protein in the body that causes inflammation, helping to reduce pain and swelling. ^{1 2 3 4 5}

Is Adalimumab (Humira) generally safe for humans?

Adalimumab, also known as Humira, has been used for over 10 years and is generally considered safe, but it can increase the risk of serious infections like tuberculosis. Common side effects include reactions at the injection site and mild infections, while rare side effects may include heart issues, skin rashes, and neurological problems. Patients should be screened and monitored closely during treatment. ^{6 7 8 9 10}

How is the drug Adalimumab unique in treating arthritis?

Adalimumab is unique because it is a fully human monoclonal antibody that specifically targets and neutralizes TNF-alpha, a protein involved in inflammation, and it can be used alone or with other medications like methotrexate. It is administered as a subcutaneous injection and has shown rapid and sustained effectiveness in reducing symptoms and slowing joint damage in arthritis patients. ^{4 11 12 13 14}

What is the purpose of this trial?

This study will examine the effectiveness of administering adalimumab as a treatment for patients in the early stages of steroid-dependent immune checkpoint Inhibitor associated inflammatory arthritis (ir-IA). Adalimumab (ADA) is a TNF inhibitor (TNFi) that is well established as a standard of care treatment for numerous types of inflammatory arthritis. It is hoped that adalimumab at the early stages of the ir-IA will reduce the symptoms and therefore reduce the need for steroids. This study is a pragmatic randomized clinical trial. Patients will be randomized 1:1 to each treatment group. To evaluate the steroid sparing effect of early induction six doses of Adalimumab will be administered to patients in the study treatment arm as compared to the usual standard of care of a predefined corticosteroid regimen and taper at 12 weeks administered in the control group.

Eligibility Criteria

This trial is for adults over 18 with arthritis that started during or within 4 weeks after immune checkpoint inhibitor therapy, and doesn't fully improve with low-dose steroids. Participants must have swollen joints or related inflammation, no recent tuberculosis, and must have given consent.

Inclusion Criteria

I have had swelling in my joints or tendons diagnosed as new arthritis in the last 6 months.

I started immunotherapy before my arthritis began.

I have tested negative for tuberculosis in the last year.

Exclusion Criteria

I have been diagnosed with inflammatory arthritis or another rheumatic disease before this current episode.

Inability to participate in follow-up visits

I have a history of heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses or a standard corticosteroid regimen

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person)

Treatment Details

Interventions

• Adalimumab

Trial Overview The study tests if early treatment with Adalimumab can reduce symptoms of inflammatory arthritis caused by cancer immunotherapy better than the usual steroid regimen. Patients are randomly assigned to receive either Adalimumab or Prednisone.

Participant Groups

Group I: Standard of care group Active Control 1 Intervention

Prednisone 10 mg daily for 2 weeks, then taper by 2.5 mg every 2 weeks until stopped.

Group II: Adalimumab group Active Control 2 Interventions

Adalimumab 40 mg subcutaneous every 2 weeks for 6 doses (12 weeks) + Prednisone 10 mg daily for 2 weeks, tapering by 2.5 mg every 2 weeks until stopped.

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

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Tom Appleton

Lead Sponsor

Trials

1

Recruited

30+

Western University

Collaborator

Trials

31

Recruited

129,000+

Canadian Research Group in Immuno-Oncology

Collaborator

Trials

1

Recruited

30+

Findings from Research

In a study of 100 patients with active psoriatic arthritis who did not respond adequately to DMARDs, adalimumab significantly improved symptoms, with 39% of patients achieving an ACR20 response compared to 16% in the placebo group after 12 weeks.

Adalimumab was well tolerated, with similar rates of serious adverse events between the treatment and placebo groups, and no serious infections reported during therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. Genovese, MC., Mease, PJ., Thomson, GT., et al.[2022]

In a 12-week study involving 127 patients with active psoriatic arthritis, adalimumab significantly improved joint and skin symptoms, with ACR20, ACR50, and ACR70 response rates of 78.0%, 55.9%, and 21.3%, respectively.

Adalimumab was well tolerated, with only three serious adverse events reported, none of which were linked to the treatment, indicating a favorable safety profile similar to previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses to adalimumab in patients with active psoriatic arthritis who have not adequately responded to prior therapy: effectiveness and safety results from an open-label study. Gladman, DD., Sampalis, JS., Illouz, O., et al.[2022]

In a study of 180 early rheumatoid arthritis patients, adding adalimumab to methotrexate and triamcinolone did not significantly increase the percentage of patients achieving low disease activity (DAS28CRP<3.2) at 12 months, with 80% in the adalimumab group and 76% in the placebo group.

However, the adalimumab group showed significant improvements in overall disease activity scores, remission rates, and quality of life measures compared to the placebo group, indicating that while it may not increase the target achievement rate, it enhances patient outcomes in other important areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial. Hørslev-Petersen, K., Hetland, ML., Junker, P., et al.[2022]

Adalimumab (ADA) is an effective treatment for rheumatoid arthritis (RA) and other inflammatory conditions, and can be used alone or with other medications like methotrexate.

This study compares the safety and effectiveness of ADA with other TNF-α inhibitors, etanercept and infliximab, highlighting the need for more direct comparisons in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. Voulgari, PV., Kaltsonoudis, E., Papagoras, C., et al.[2022]

Intensifying treatment with infliximab, a TNF-α-inhibitor for rheumatoid arthritis, may improve clinical outcomes, especially when increasing the frequency of administration rather than the dose, based on evidence from 11 studies.

However, the overall evidence is weak due to the lack of control groups and contradictory results in high-quality trials, highlighting the need for more robust, prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of treatment intensification with adalimumab, etanercept and infliximab in rheumatoid arthritis: a systematic review of cohort studies with focus on dose. Eng, G., Stoltenberg, MB., Szkudlarek, M., et al.[2018]

In a study involving 15,132 patients with rheumatoid arthritis, adalimumab was found to have a well-established safety profile, with serious infections occurring at a low rate of 4.7 events per 100 patient-years and no significant laboratory abnormalities compared to placebo.

The analysis also indicated that pregnancy outcomes for women exposed to adalimumab were similar to those of unexposed women with rheumatoid arthritis and healthy women, with no increased risk of major birth defects or spontaneous abortions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Burmester, GR., Landewé, R., Genovese, MC., et al.[2022]

Adalimumab is an effective treatment for rheumatoid arthritis and is expected to be approved for other conditions like psoriasis and ankylosing spondylitis, with a favorable side effect profile compared to traditional treatments, as it does not require regular lab monitoring.

However, it carries a two-fold increased risk of serious infections, particularly tuberculosis, and should not be used during active infections; careful screening and monitoring for side effects are essential for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of side effects. Scheinfeld, N.[2022]

Adalimumab has been shown to be generally safe and well tolerated in patients with rheumatoid arthritis, based on safety data from over 10,000 patients and 12,506 patient-years of exposure in clinical trials.

The rate of serious infections was consistent with previous reports, and after implementing tuberculosis screening, the incidence of TB cases decreased significantly, indicating effective monitoring and management of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Schiff, MH., Burmester, GR., Kent, JD., et al.[2022]

In a comprehensive analysis of 19,041 patients across 36 clinical trials, adalimumab showed stable rates of serious adverse events (SAE) over time in rheumatoid arthritis and similar or lower rates in other immune-mediated inflammatory diseases.

The overall rates of malignancies and mortality in adalimumab-treated patients were comparable to those in the general population, indicating that adalimumab is safe for long-term use in treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Burmester, GR., Mease, P., Dijkmans, BA., et al.[2023]

Adalimumab is generally safe for treating psoriasis, with most side effects being mild, such as injection site reactions and upper respiratory infections, which typically do not require stopping the medication.

Serious adverse effects, although rare, can include severe infections and autoimmune conditions, highlighting the need for careful patient screening and monitoring during treatment and for five months afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. Ferran, M., Pujol, RM.[2015]

Adalimumab is a fully human monoclonal antibody that targets TNF-alpha, a key protein involved in inflammation, making it effective for treating rheumatoid arthritis.

Clinical trials have shown promising results for adalimumab, and it is also being tested for other inflammatory conditions like psoriasis and psoriatic arthritis, indicating its potential broad therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab (HUMIRA): a review. Scheinfeld, N.[2015]

Adalimumab effectively targets and neutralizes tumor necrosis factor (TNF), a key player in psoriatic arthritis (PsA), leading to significant reductions in both joint and skin symptoms in clinical trials.

The treatment not only improved symptoms but also inhibited structural damage and enhanced patients' quality of life and disability measures, with a good safety profile reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: an anti-TNF agent for the treatment of psoriatic arthritis. Mease, PJ.[2019]

Adalimumab, a monoclonal antibody that targets TNF-alpha, has been shown to significantly improve symptoms of rheumatoid arthritis in patients who did not respond adequately to other treatments, with higher response rates (ACR20, ACR50, ACR70) compared to placebo over 24-52 weeks.

The treatment not only provides rapid and sustained efficacy but also slows down joint damage and enhances quality of life, making it a valuable option for adults with active rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of its use in rheumatoid arthritis. Bang, LM., Keating, GM.[2018]

In a phase I clinical study involving 164 healthy Chinese male subjects, the biosimilar adalimumab showed bioequivalence to Humira® with pharmacokinetic parameters falling within the acceptable range of 80%-125%.

Both adalimumab and Humira® demonstrated similar levels of immunogenicity and safety, indicating that the biosimilar can be considered a safe and effective alternative to the original drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers. Wang, Y., Gao, Z., Liu, Z., et al.[2022]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. [2022]

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

Responses to adalimumab in patients with active psoriatic arthritis who have not adequately responded to prior therapy: effectiveness and safety results from an open-label study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind, parallel-group, placebo-controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Adalimumab in the treatment of rheumatoid arthritis. [2022]

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

Efficacy of treatment intensification with adalimumab, etanercept and infliximab in rheumatoid arthritis: a systematic review of cohort studies with focus on dose. [2018]

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

Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. [2022]

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

Adalimumab: a review of side effects. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. [2022]

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

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. [2023]

10. Spain pubmed.ncbi.nlm.nih.gov

[Safety of adalimumab]. [2015]

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

Adalimumab (HUMIRA): a review. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Adalimumab: an anti-TNF agent for the treatment of psoriatic arthritis. [2019]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Adalimumab: a review of its use in rheumatoid arthritis. [2018]

14. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, single-dose, two-way, parallel phase I clinical study comparing the pharmacokinetics and safety of adalimumab injecta and Humira® in healthy Chinese male volunteers. [2022]