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

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ClinicalTrials.gov Identifier: NCT04731831
Recruitment Status : Recruiting
First Posted : February 1, 2021
Last Update Posted : February 1, 2021
Sponsor:
Information provided by (Responsible Party):
Karen Buch Lauridsen, Aalborg University Hospital

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
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.

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Study Type : Observational
Estimated 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 : August 1, 2020
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arthritis

Group/Cohort
Patient with arthritis starting infliximab or adalimumab
Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab



Primary Outcome Measures :
  1. Treatment response [ Time Frame: 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 :
  1. Immunogenesity [ Time Frame: 12 months ]
    Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies

  2. Drug koncentration [ Time Frame: 12 months ]
    Plasma koncentration of infliximab or adalimumab

  3. Concentration of markers of inflammation [ Time Frame: 12 months ]
    C-reactive protein (CRP), IL1, .

  4. Concentration of autoantibodies [ Time Frame: Day 1 ]
    ANA, ACPA, IgM-RF

  5. HLA-type [ Time Frame: Day 1 ]
    Genomic determination of Human Leucocyte antigens


Biospecimen Retention:   Samples With DNA
EDTA Whole Blood EDTA-plasma, EDTA-buffy coat, serum.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients at department of Rheumatology in Aalborg Universityhospital, Denmark. Other sites in Jutland, Denmark may be inkluded later.
Criteria

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:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04731831


Contacts
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Contact: Karen B Lauridsen, MD 0045 097665595 kabula@rn.dk

Locations
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Denmark
Department of rheumatology Recruiting
Aalborg, Denmark, 8000
Sponsors and Collaborators
Aalborg University Hospital
Investigators
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Principal Investigator: Lene Dreyer, MD, Prof. Department of Clinical Medicine, Aalborg University and Aalborg University Hospital
Publications:

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Responsible Party: Karen Buch Lauridsen, Principal Investigator, Aalborg University Hospital
ClinicalTrials.gov Identifier: NCT04731831    
Other Study ID Numbers: N-20200063
First Posted: February 1, 2021    Key Record Dates
Last Update Posted: February 1, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Spondylitis
Arthritis
Arthritis, Rheumatoid
Arthritis, Psoriatic
Spondylitis, Ankylosing
Joint Diseases
Musculoskeletal Diseases
Bone Diseases, Infectious
Infection
Bone Diseases
Spinal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Spondylarthropathies
Spondylarthritis
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Ankylosis