Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.

Sponsor

Aalborg University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04731831

Collaborator

(none)

120

Enrollment

Location

46.9

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to explore whether the influence of gender, tobacco smoking and obesity on treatment response in tumor necrosis factor inhibitors (TNFIs) can be explained by high degree of inflammation, human leucocyte antigen (HLA) type, autoantibodies, TNF and TNFI concentration and presence of ADA.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid Arthritis, Psoriatic Spondylitis, Ankylosing

Detailed Description

Tumor necrosis factor inhibitors (TNFIs) have been uses with success since 1999 in Denmark in treatment of various inflammatory diseases, eg. rheumatoid arthritis (RA), Chrohn's disease, psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

TNFIs block a central cytokine in the inflammatory process, tumor necrosis factor (TNF).

Because the drugs are large proteins, they are prone to trigger an immune response and elicit anti-drug antibodies(ADA).

Epidemiologic studies have revealed that groups of patients (women, tobacco smokers, obese patients) with inflammatory rheumatic diseases have a lower response to TNFIs. The reasons for this are not fully elucidated. The hypothesis is that immunogenicity and changed pharmacokinetic of TNFI are causes of the inferior response.

The investigators will carry out a prospective clinical studies of 120 arthritis patients (RA, PsA and AS) initiating treatment with adalimumab or infliximab. The patients will be followed for 12 months and will be registered in DANBIO as normal praxis. Blood samples will be collected at baseline, 2, 4 and 12 months or at termination of the treatment.

Genotypes, autoantibodies, inflammation markers, TNFI and ADA will be measured.

The aim of the study is to explore:

A: If differences between men and women with respect to different markers of inflammation, human leucocyte antigen (HLA), autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among women.

B: If differences between smokers and non-smokers with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among patients with arthritis who smoke tobacco.

C: If differences between obese and normal weight patients with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment.

The study will contribute with new knowledge, which hopefully can make the treatment more personalized and efficient.

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Characterization of Immunogenicity of Tumor Necrosis Factor Inhibitors in Arthritis Patients With Poorer Treatment Response Due to Gender, Obesity and Smoking Status.

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Patient with arthritis starting infliximab or adalimumab Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab

Outcome Measures

Primary Outcome Measures

Treatment response [12 months]
Changes in disease activity score according to the diagnose. A reduction in the disease activity score indicates a good treatment response. Disease Activity Score 28 joints with C-reactive protein (DAS28-CRP) Disease Activity in Psoriasis Arthritis (DAPSA) Ankylosing Spondylitis Activity Score (ASDAS) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Bath Ankylosin Spondylitis Functional Index (BASFI)

Secondary Outcome Measures

Immunogenesity [12 months]
Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies
Drug koncentration [12 months]
Plasma koncentration of infliximab or adalimumab
Concentration of markers of inflammation [12 months]
C-reactive protein (CRP), IL1, .
Concentration of autoantibodies [Day 1]
ANA, ACPA, IgM-RF
HLA-type [Day 1]
Genomic determination of Human Leucocyte antigens

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients > 18 years
Diagnosed with RA, PsA or AS.
Starting treatment with infliximab or adalimumab.
Co- treatment with csDMARD or glucocorticoid is acceptable.
No new bDMARD is initiated at the time of sampling.

Exclusion Criteria:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of rheumatology	Aalborg		Denmark	8000

Sponsors and Collaborators

Aalborg University Hospital

Investigators

Principal Investigator: Lene Dreyer, MD, Prof., Department of Clinical Medicine, Aalborg University and Aalborg University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Karen Buch Lauridsen, Principal Investigator, Aalborg University Hospital

ClinicalTrials.gov Identifier:

NCT04731831

Other Study ID Numbers:

N-20200063

First Posted:

Feb 1, 2021

Last Update Posted:

Feb 1, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Spondylitis

Arthritis

Arthritis, Rheumatoid

Arthritis, Psoriatic

Spondylitis, Ankylosing

Study Results

No Results Posted as of Feb 1, 2021