NCT04222920

Brief Summary

Several prior studies have shown that dose reduction or discontinuation of tumor necrosis factor (TNF)-inhibitors, like adalimumab, is possible in substantial number of patients with a rheumatic disease without an increase in disease activity. Prior studies showed that patients with concentrations higher than 5 mg/L are overexposed to adalimumab and can safely reduce the dose. In the first phase of treatment, an adalimumab concentration of 5mg/L is needed to achieve adequate clinical response. However to control disease activity after 28 weeks, lower concentration than 5 mg/L are probably sufficient. Recent published data suggest that concentrations of 0.1-0.5 mg/L are enough to control TNF blockade in this state. Yet, a study which investigates the lowest effective drug serum concentration is missing so far. The hypothesis is that serum adalimumab concentration of 2 mg/L is sufficient to control disease activity.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P25-P50 for phase_4 rheumatoid-arthritis

Timeline
Completed

Started Mar 2020

Typical duration for phase_4 rheumatoid-arthritis

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 7, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 10, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2020

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 11, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 11, 2023

Completed
Last Updated

November 18, 2023

Status Verified

November 1, 2023

Enrollment Period

3.5 years

First QC Date

January 7, 2020

Last Update Submit

November 17, 2023

Conditions

Rheumatoid Arthritis

Keywords

AdalimumabRheumatoid arthritisTherapeutic Drug MonitoringDrug levelDose reduction

Outcome Measures

Primary Outcomes (1)

  • Mean time weighted DAS28-CRP

    The difference in mean time weighted DAS28-CRP after 28 weeks between dose reduction aiming serum adalimumab concentration of 5mg/L and 2mg/L

    after 24 weeks

Secondary Outcomes (4)

  • Mean time weighted DAS28-CRP

    after 12 weeks

  • Number of flares

    after 24 weeks

  • Direct medical costs

    after 24 weeks

  • Drug levels

    after 12 and 24 weeks

Study Arms (2)

Low serum drug concentration

EXPERIMENTAL

Adalimumab dose reduction aiming a drug level of 2 mg/L

Other: Dose reduction to 2mg/LDrug: Adalimumab

High serum drug concentration

ACTIVE COMPARATOR

Adalimumab dose reduction aiming a drug level of 5 mg/L

Other: Dose reduction to 5mg/LDrug: Adalimumab

Interventions

Dose reduction to 2mg/LOTHER

Adalimumab dose reduction aiming drug concentration of 2mg/L

Low serum drug concentration
Dose reduction to 5mg/LOTHER

Adalimumab dose reduction aiming drug concentration of 5mg/L

High serum drug concentration
AdalimumabDRUG

Adalimumab

High serum drug concentrationLow serum drug concentration

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Rheumatoid arthritis patient, according to ACR 1987 or ACR/EULAR 2010
  • Treated for at least 28 weeks with adalimumab
  • Adalimumab trough concentration \>5mg/L
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Reade Rheumatology Research Institute

Amsterdam, North Holland, 1056AB, Netherlands

Location

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: 26324949BACKGROUND

  • 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: 26764260BACKGROUND

  • 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: 28939629BACKGROUND

  • 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: 24326008BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Gertjan Wolbink, MD, PhD

    Reade Rheumatology Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Masking Details
The participants are kept ignorant of the group to which they have been assigned
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Patients with rheumatoid arthritis treated with adalimumab for at least 28 weeks and a serum adalimumab concentration above 5 mg/L will be randomly assigned to dose reduction by extending their dosing interval aiming a drug level of 2 mg/L or aiming a drug level of 5 mg/L
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2020

First Posted

January 10, 2020

Study Start

March 1, 2020

Primary Completion

September 11, 2023

Study Completion

September 11, 2023

Last Updated

November 18, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will share

To avoid duplication of research, the gathered data will be shared once all desirable data analysis have been performed and the results are published

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)