Proactive Therapeutic Drug Monitoring Based Adalimumab Therapy Optimization in Patients With Rheumatoid Arthritis (TDM-RA)

Current standard of care of rheumatoid arthritis (RA) management includes a routine clinical assessment of disease activity to adjust therapy. For the most part, therapy adjustment for therapy non-response and/or suboptimal therapy response leads to therapy switch within the same class of therapy or to a different class of therapy. The lack of objective data to titrate dose of a given therapeutic agent for maximal possible efficacy makes it difficult for providers and payors to titrate dose as needed.

Therapeutic drug monitoring (TDM) provides objective data for a proactive and individualized therapy optimization based on serum drug levels and the presence or absence of anti-drug antibodies. Maintaining optimal trough drug concentration is a proven concept of therapeutics. With respect to adalimumab, this approach helps to maximize therapeutic efficacy and prevent anti-adalimumab antibody development. However, lack of drug and disease state specific published data creates a barrier for a wider adoption of TDM into clinical practice.

The objective of this single site, open label, randomized, parallel group pilot study is to investigate whether proactive therapeutic drug monitoring based adalimumab dose optimization results in higher rate of achieving and/or maintaining therapeutic goal compared to standard of care in patients with rheumatoid arthritis.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Therapeutic drug monitoring (TDM)

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center, Rheumatology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis
• Starting or already being treated with standard dose adalimumab, 40 mg subcutaneously (SQ) every two weeks
• Good medication adherence rate defined as Proportion of Days Covered (PDC) 80% and above

Exclusion Criteria:

• Detectable anti-adalimumab antibodies
• Overlapping immune mediated diseases
• Steroid therapy for more than 2 months prior to study enrollment
• Poor medication adherence rate (PDC < 80%)
• History of recurrent infection resulting in therapy pause
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDM based adalimumab dose optimization group; Therapeutic drug monitoring (TDM) provides an opportunity for a proactive and individualized therapy optimization based on serum drug concentration and anti-drug antibodies development.	Other: Therapeutic drug monitoring (TDM); Serum trough level of adalimumab and anti-adalimumab antibody will be obtained at time of enrollment and every 3 months until the end of the study. Adalimumab dose optimization goal will be to achieve trough drug level in the range of 5 -8 μg/mL.
No Intervention: Standard of care; Standard of care practice for RA management is based on disease activity guided therapy adjustments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 months change in proportion of patients with RA who achieve and maintain remission or low disease activity	Remission and low disease activity is defined as a Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score of <2.6 and 2.6 -3.2 respectively. A DAS-28 reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement.	baseline, 3 months
6 months change in proportion of patients with RA who achieve and maintain remission or low disease activity	Remission and low disease activity is defined as a Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score of <2.6 and 2.6 -3.2 respectively. A DAS-28 reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement.	baseline, 6 months
9 months change in proportion of patients with RA who achieve and maintain remission or low disease activity	Remission and low disease activity is defined as a Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score of <2.6 and 2.6 -3.2 respectively. A DAS-28 reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement.	baseline, 9 months
12 months change in proportion of patients with RA who achieve and maintain remission or low disease activity	Remission and low disease activity is defined as a Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score of <2.6 and 2.6 -3.2 respectively. A DAS-28 reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement.	baseline, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of participants who achieved low or near remission disease severity	This will be assessed with the Routine Assessment of Patient Index Data 3 (RAPID3) which is a composite disease activity index consisting of the 3 Patient Reported Outcomes, disability, pain, and patient global assessment of disease activity. Scores can range from 0 to 30 and low or near remission disease severity is defined as patients with RAPID3 disease severity score of 3.1-6 and ≤3 respectively.	baseline, 3 months, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: American Society of Health-System Pharmacists
• Investigators: Principal Investigator: Amanuel Kehasse, PharmD, PhD, Boston Medical Center, Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2022
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Therapeutic drug monitoring (TDM); Optimal trough drug concentration; Adalimumab dose optimization; Routine Assessment of Patient Index Data 3 (RAPID3)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: H-42873

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No