Therapeutic Drug Monitoring for Rheumatoid Arthritis

(TDM-RA Trial)

Overseen By Marcin Trojanowski, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Boston Medical Center

Must be taking: Adalimumab

Disqualifiers: Anti-adalimumab antibodies, Immune diseases, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to see if monitoring and adjusting the levels of the drug adalimumab in the blood helps patients with rheumatoid arthritis achieve better treatment outcomes compared to standard care. Adalimumab is a therapeutic option for patients with moderate to severe rheumatoid arthritis.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. However, it requires that you are either starting or already being treated with adalimumab. If you are on other medications, it's best to discuss with the trial coordinators.

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

Research shows that Adalimumab, when used with methotrexate, can help achieve remission (a state where symptoms are reduced or disappear) and prevent joint damage in rheumatoid arthritis patients. It has been effective in increasing remission rates and improving quality of life in early rheumatoid arthritis. ^{1 2 3 4 5}

Is adalimumab (Humira) safe for humans?

Adalimumab, also known as Humira, has been used for over 10 years and is generally considered safe for humans. It has a well-established safety profile, with the most common side effects being respiratory infections and, in rare cases, reactivation of tuberculosis. These safety findings apply to its use in conditions like rheumatoid arthritis and other similar diseases. ^{6 7 8 9 10}

What makes the drug Adalimumab unique for treating rheumatoid arthritis?

Adalimumab is a biologic drug that works by inhibiting tumor necrosis factor (TNF), a substance in the body that causes inflammation in rheumatoid arthritis. Unlike some other treatments, it can form complexes with TNF, which may affect its effectiveness and lead to the development of anti-drug antibodies that can reduce its long-term efficacy. ^{4 11 12 13 14}

Research Team

Amanuel Kehasse, PharmD, PhD

Principal Investigator

Boston Medical Center, Pharmacy

Eligibility Criteria

This trial is for people with rheumatoid arthritis who are starting or already on standard adalimumab therapy, taking it every two weeks and have a good track record of taking their medication. It's not for those who've been on steroids long-term, have poor medication adherence, are pregnant or breastfeeding, have detectable anti-adalimumab antibodies, other immune diseases, or a history of infections affecting treatment.

Inclusion Criteria

Good medication adherence rate defined as Proportion of Days Covered (PDC) 80% and above

I have been diagnosed with rheumatoid arthritis.

I am taking or starting adalimumab, 40 mg under the skin every two weeks.

Exclusion Criteria

Pregnant or lactating

Overlapping immune mediated diseases

I've had infections that stopped my treatment before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adalimumab with therapeutic drug monitoring for dose optimization

12 months

Monthly visits for drug monitoring and dose adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Adalimumab
• Therapeutic drug monitoring (TDM)

Trial Overview The study tests if monitoring drug levels in the blood (therapeutic drug monitoring) to adjust doses can better achieve treatment goals in rheumatoid arthritis compared to usual care without such monitoring. Participants will be randomly assigned to either continue with standard care or receive dose adjustments based on their blood test results.

Participant Groups

Group I: TDM based adalimumab dose optimization group Experimental Treatment 1 Intervention

Therapeutic drug monitoring (TDM) provides an opportunity for a proactive and individualized therapy optimization based on serum drug concentration and anti-drug antibodies development.

Group II: Standard of care Active Control 1 Intervention

Standard of care practice for RA management is based on disease activity guided therapy adjustments.

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?

Boston Medical Center

Lead Sponsor

Trials

410

Recruited

890,000+

American Society of Health-System Pharmacists

Collaborator

Trials

5

Recruited

330+

Findings from Research

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 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 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]

References

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

Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from adalimumab studies. [2018]

2. 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]

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

Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study. [2020]

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

What Is the Clinical Relevance of TNF Inhibitor Immunogenicity in the Management of Patients With Rheumatoid Arthritis? [2021]

5. England pubmed.ncbi.nlm.nih.gov

Reprint of "Anti-therapeutic antibodies and their clinical impact in patients treated with the TNF antagonist adalimumab". [2018]

6. 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]

7. Spain pubmed.ncbi.nlm.nih.gov

Role of adalimumab, a novel TNF antagonist in advancing rheumatoid arthritis control. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. [2022]

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

Long-term use of adalimumab in the treatment of rheumatic diseases. [2020]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Development of a sensitive biochemical assay for the detection of tofacitinib adherence. [2023]

12. Spain pubmed.ncbi.nlm.nih.gov

Comparative study of both versions of an immunoassay commercialized for therapeutic drug monitoring of adalimumab in rheumatoid arthritis. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Clinical utility of random anti-tumour necrosis factor drug testing and measurement of anti-drug antibodies on long-term treatment response in rheumatoid arthritis. [2023]

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

Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay. [2020]