Adalimumab Drug Optimisation in Rheumatoid Arthritis Using Therapeutic Drug Monitoring

NCT04194827 | Recruiting Phase 4 DMC

• 1 other identifier: ADDORA
• Study Type: interventional
• Target: 267
• Locations: 1 country
• Sites: 1

Brief Summary

Several prior studies have shown that dose reduction of Tumor Necrosis Factor (TNF)-inhibitors like adalimumab is possible in substantial number of rheumatic disease patients without an increase in disease activity. Biologic therapy is expensive, and is associated with patient burden as dose dependant risk for serious infections . A dose reduction will decrease the risk of side effects and result in substantial cost savings. Currently, most clinicians use Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI) to monitor dose tapering strategies. Although this approach is cost-effective, it might be improved by information on the extent of drug levels, as several studies have shown that adalimumab drug levels are associated with clinical outcome. Therefore, a study comparing dose reduction strategy using drug concentration with dose reduction strategy using disease activity is timely

Conditions

Rheumatoid Arthritis

Keywords

Adalimumab; Rheumatoid arthritis; Therapeutic Drug Monitoring; Drug level; Dose reduction

Outcome Measures

Primary Outcomes (1)

• Medical costs

  Direct medical costs associated with adalimumab dose reduction using drug concentration versus using disease activity scores

  52 weeks

Secondary Outcomes (7)

• Mean time weighted DAS28-CRP

  at 16, 28, 52 and 80 weeks

• Direct medical costs

  at week 28 and week 80

• Indirect medical costs

  at 28, 52 and 80 weeks

• Patients with DAS28-CRP<2.9

  at 52 and 80 weeks

• Number of flares

  at 52 and 80 weeks

Study Arms (2)

Concentration guided dose reducion

EXPERIMENTAL

Dose reduction of adalimumab will be based on adalimumab through concentration after 16 weeks of treatment with adalimumab.

Diagnostic Test: Adalimumab serum trough concentration; Drug: Adalimumab

Disease activity quided dose reduction

ACTIVE COMPARATOR

Dose reduction of adalimumab will be based on disease activity after 28 weeks of treatment with adalimumab

Diagnostic Test: Disease activity; Drug: Adalimumab

Interventions

Adalimumab serum trough concentration DIAGNOSTIC_TEST

Dose reduction based on adalimumab serum trough concentration

Concentration guided dose reducion

Disease activity DIAGNOSTIC_TEST

Dose reduction based on adalimumab diseas activity

Disease activity quided dose reduction

Adalimumab DRUG

Adalimumab

Concentration guided dose reducion; Disease activity quided dose reduction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Rheumatoid arthritis patient, according to ACR 1987 or ACR/EULAR 2010 criteria;
• Starting adalimumab as the first biological therapy
• Who has agreed to participate (written informed consent);
• Age 18 years or older.

You may not qualify if:

• Scheduled surgery during the follow-up of the study or other pre-planned reasons for treatment discontinuation;
• Life expectancy shorter than follow-up period of the study;
• Other disease that might flare if adalimumab is tapered like psoriasis, inflammatory bowel disease.

Sponsors & Collaborators

• Reade Rheumatology Research Institute: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Sint Maartenskliniek: collaborator

Study Sites (1)

Reade Rheumatology Research Institute

Amsterdam, North Holland, 1056AB, Netherlands

RECRUITING

Related Publications (4)

• Chen DY, Chen YM, Hsieh TY, Hung WT, Hsieh CW, Chen HH, Tang KT, Lan JL. Drug trough levels predict therapeutic responses to dose reduction of adalimumab for rheumatoid arthritis patients during 24 weeks of follow-up. Rheumatology (Oxford). 2016 Jan;55(1):143-8. doi: 10.1093/rheumatology/kev298. Epub 2015 Aug 31.

  PMID: 26324949 BACKGROUND

• Kievit W, van Herwaarden N, van den Hoogen FH, van Vollenhoven RF, Bijlsma JW, van den Bemt BJ, van der Maas A, den Broeder AA. Disease activity-guided dose optimisation of adalimumab and etanercept is a cost-effective strategy compared with non-tapering tight control rheumatoid arthritis care: analyses of the DRESS study. Ann Rheum Dis. 2016 Nov;75(11):1939-1944. doi: 10.1136/annrheumdis-2015-208317. Epub 2016 Jan 13.

  PMID: 26764260 BACKGROUND

• l'Ami MJ, Krieckaert CL, Nurmohamed MT, van Vollenhoven RF, Rispens T, Boers M, Wolbink GJ. Successful reduction of overexposure in patients with rheumatoid arthritis with high serum adalimumab concentrations: an open-label, non-inferiority, randomised clinical trial. Ann Rheum Dis. 2018 Apr;77(4):484-487. doi: 10.1136/annrheumdis-2017-211781. Epub 2017 Sep 22.

  PMID: 28939629 BACKGROUND

• Pouw MF, Krieckaert CL, Nurmohamed MT, van der Kleij D, Aarden L, Rispens T, Wolbink G. Key findings towards optimising adalimumab treatment: the concentration-effect curve. Ann Rheum Dis. 2015 Mar;74(3):513-8. doi: 10.1136/annrheumdis-2013-204172. Epub 2013 Dec 10.

  PMID: 24326008 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gertjan Wolbink, PhD

  Reade Rheumatology Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sadaf Atiqi, MD

CONTACT

0031-202421641; s.atiqi@reade.nl

Femke Hooijberg

CONTACT

0031202421633; f.hooijberg@reade.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: During every study visit the joints of all patients will be examined for pain and swelling by a blinded nurse or physician. The number of painful and swollen joints will be used to calculate the DAS28 score, the primary outcome of the study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Rheumatoid arthritis patients treated with adalimumab will be randomly assigned to a dose reduction strategy using disease activity scores or to a dose reduction strategy using serum drug concentrations

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 11, 2019
• Study Start: March 1, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Six months after the study is published the data will be shared
• Access Criteria: Researchers with demonstrable interest in autoimmunity, biologicals, or TDM can contact the investigators of the trial if they are interested in gaining access to the data. Depending on their research objectives the data will be shared

Locations

NL (1)