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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to enhance rheumatoid arthritis (RA) treatments by adjusting medication based on blood tests. It uses therapeutic drug monitoring (TDM) to determine if maintaining specific drug levels in the blood can improve outcomes with adalimumab (also known as Humira). Participants will either have their adalimumab dose adjusted using TDM or continue with the standard treatment approach. The trial seeks individuals with rheumatoid arthritis who are already on adalimumab and have been consistently taking their medication. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could improve treatment effectiveness for RA patients.

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 prior data suggests that therapeutic drug monitoring is safe for rheumatoid arthritis management?

Research shows that adalimumab is generally safe and well-tolerated for people with rheumatoid arthritis. Studies have found that long-term use usually doesn't lead to serious safety issues. Global clinical data highlight adalimumab's positive safety profile.

Therapeutic drug monitoring (TDM) helps maintain drug levels in the blood within the right range, allowing for personalized dose adjustments of adalimumab. Early TDM in rheumatic diseases shows that maintaining steady drug levels can help patients continue the medication longer without problems. It also lowers the chance of developing anti-drug antibodies, which can reduce the drug's effectiveness.

Overall, while adalimumab has shown safety, TDM might further improve treatment by personalizing the dose and reducing potential issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores therapeutic drug monitoring (TDM) for optimizing the use of adalimumab in treating rheumatoid arthritis (RA). Unlike the standard of care, which typically involves adjusting treatment based on disease activity, TDM allows for a proactive, personalized approach by measuring drug levels and checking for anti-drug antibodies in the blood. This method could lead to more precise dosing and potentially better outcomes for patients, making treatment more effective and reducing unnecessary medication use.

What evidence suggests that therapeutic drug monitoring is effective for rheumatoid arthritis?

Research has shown that adjusting adalimumab doses using therapeutic drug monitoring (TDM), tested in one arm of this trial, can improve outcomes for people with rheumatoid arthritis. Studies have found that maintaining adalimumab levels above 4.0 mg/L associates with low disease activity or remission. Early TDM of adalimumab helps predict the drug's effectiveness over a year. In real-world settings, TDM effectively manages rheumatoid arthritis. This approach is promising because it customizes treatment to individual needs, potentially increasing effectiveness. ^{1 3 5 6 7}

Who Is on the Research Team?

Amanuel Kehasse, PharmD, PhD

Principal Investigator

Boston Medical Center, Pharmacy

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11865102/

“early therapeutic drug monitoring of adalimumab” - PMC Early TDM of adalimumab in rheumatic diseases shows that low drug exposure predicts reduced drug survival at 52 weeks.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05460390

Proactive Therapeutic Drug Monitoring Based Adalimumab ... Therapeutic drug monitoring (TDM) provides objective data for a proactive and individualized therapy optimization based on serum drug levels and the presence or ...

3. rmdopen.bmj.com rmdopen.bmj.com/content/10/4/e004888

Therapeutic serum level for adalimumab in rheumatoid ... Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022202X23001604

Real-World Implementation and Outcomes of Adalimumab ... Adalimumab TDM has shown promise in the real-world care of IMIDs including rheumatoid arthritis, inflammatory bowel disease, and noninfectious uveitis, but has ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8380594/

Cost-Effectiveness of Therapeutic Drug Monitoring-Guided ... To assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1798196/

Safety analyses of adalimumab (HUMIRA) in global clinical ... Analyses of these data demonstrate that long term adalimumab treatment is generally safe and well tolerated in patients with RA. Keywords: adalimumab, ...

7. jrheum.org jrheum.org/content/47/7/959

Longterm, Real-world Safety of Adalimumab in ... This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry.