Proactive Therapeutic Drug Monitoring Based Adalimumab Therapy Optimization in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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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.

Official Title
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Proactive Therapeutic Drug Monitoring Based Adalimumab Therapy Optimization in Patients With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Therapeutic drug monitoring (TDM)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TDM based adalimumab dose optimization group<br>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)<br>* 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.<br>|
| No Intervention: Standard of care<br>Standard of care practice for RA management is based on disease activity guided therapy adjustments. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic drug monitoring (TDM), Optimal trough drug concentration, Adalimumab dose optimization, Routine Assessment of Patient Index Data 3 (RAPID3)