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

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04731831
• Other study ID #: N-20200063
• Status: Recruiting
• Start date: August 1, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: September 2022
• Source: Aalborg University Hospital
• Contact: Karen B Lauridsen, MD
• Phone: 0045 097665595
• Email: kabula[@]rn.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2024
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

-

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Arthritis, Rheumatoid
• Spondylitis
• Spondylitis, Ankylosing

Locations

Country	Name	City	State
Denmark	Department of rheumatology	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment response	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)	12 months
Secondary	Immunogenesity	Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies	12 months
Secondary	Drug koncentration	Plasma koncentration of infliximab or adalimumab	12 months
Secondary	Concentration of markers of inflammation	C-reactive protein (CRP), IL1, .	12 months
Secondary	Concentration of autoantibodies	ANA, ACPA, IgM-RF	Day 1
Secondary	HLA-type	Genomic determination of Human Leucocyte antigens	Day 1