Therapeutic Response to Tumor Necrosis Factor-alpha (TNF-alpha) Antagonists in Rheumatoid Arthritis.

NCT05379049 | Unknown FDA Drug

• 1 other identifier: UoS
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory disease and TNF-alpha has been recognized as a triggering cytokine in the induction of joints inflammation and is involved in the pathogenesis of RA. Treatment for RA aims to reduce disease activity, prevent or manage joint deterioration and lower the risk of major comorbidities such as heart disease and stroke. The strategy of targeting cytokines has significantly increased RA patient outcomes. Therefore management with biological disease-modifying antirheumatic drugs "bDMARD" (Etanercept, Infliximab, Adalimumab) should be considered, If the treatment goal is not met with the first conventional synthetic drug modifying antirheumatic drugs (csDMARD) strategy, or if there are poor prognostic factors. The multi-biomarker disease activity test could be used to help standardise individual treatment decisions, especially in patients who failed to respond well to the traditional treatment. Iraq does not currently have specific guidelines, which might pose a risk to patients' safety. More data about the choice of bDMARD is needed in terms of tracking therapeutic response, or whether TNF or other pro-inflammatory cytokines like interleukin-6 (IL-6) is the main factor for the development and severity of RA. These data are important to improve the overall status of the patient, better choice of treatment and biomarkers to detect. There is limited information on the treatment patterns of rheumatoid arthritis (RA) across Iraq including the Kurdistan Region. Therefore, the aim of this research is to evaluate the efficacy, and clinical responses of RA patients who have been treated with different anti-TNF, as well as on answering the research hypothesis, Can plasma TNF-alpha and IL-6 be used as markers of therapeutic response to TNF alpha antagonist in patients with RA?

Conditions

Rheumatoid Arthritis; Inflammatory Arthritis; Ankylosing Spondylitis

Keywords

Rheumatoid Arthritis, Cytokines

Outcome Measures

Primary Outcomes (7)

• Comparison of Plasma Tumor Necrosis Factor alpha (TNF-α) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.

  Tumor Necrosis Factor alpha (TNF-α) is a pro-inflammatory cytokine produced by activating macrophages and T-cells that play a key role in the production of other cytokines and the induction of chronic inflammation.

  Up to 12 Weeks

• Comparison of Plasma Interleukin-6 (IL-6) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.

  Interleukin-6 (IL-6) is a major pro-inflammatory cytokine, triggers the vicious circle of escalating RA disease activity via inducing immune activation and inflammation in RA.

  Up to 12 Weeks

• Mean change of C-reactive Protein (CRP) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.

  C-reactive protein (CRP) a potential marker of systemic inflammation and is elevated in patients with rheumatoid arthritis (RA).

  Up to 12 Weeks

• Mean change of Erythrocyte Sedimentation Rate (ESR) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.

  Erythrocyte sedimentation rate (ESR) is a popular hematology test that may detect and track an increase in inflammatory activity in the body, which can be caused by autoimmune illness, infections, or malignancies.

  Up to 12 Weeks

• Complete blood count (CBC)

  A complete blood count (CBC) is a blood test used to evaluate overall health and detect a wide range of hematological disorders, including anemia.

  Up to 12 Weeks

• Assessment of Disease Activity Score (DAS)

  Disease Activity Score (DAS) is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health.

  Up to 12 weeks

• Assessment of Visual Activity Score (VAS)

  Visual Activity Score (VAS) A psychometric pain rating scale for parameters that range across a continuum of values, such as pain. The VAS pain scale ranges from "no pain" to "worst pain," and patients mark a line to indicate how they are feeling.

  Up to 12 weeks

Secondary Outcomes (2)

• A correlation between plasma Tumor Necrosis Factor alpha (TNF-α) and disease activity and severity.

  Up to 12 weeks

• A correlation between plasma Interleukin-6 (IL-6) and disease activity and severity.

  Up to 12 weeks

Interventions

Infliximab: Adalimumab; Etanercept; BIOLOGICAL

Therapeutic drug monitoring, evaluation of clinical outcomes and laboratory analysis of biomarkers

Also known as: Remicade, Remsima، Humira, amgevita، Enbrel

Eligibility Criteria

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

Study Population

\~60-80 adult patients \[≥18 years\] with Rheumatoid Arthritis from both genders registered at Rehabilitation and Rheumatology Center in Sulaymaniyah City, who are not responding to conventional DMARDs regardless of disease activity and concomitant treatments.

You may qualify if:

• Meeting the ACR/EULAR 2010 criteria for rheumatoid arthritis (RA).
• Patients (or Legal Guardian, if applicable) who are willing to give informed consent for the study period-time follow up.
• Concomitant DMARDs
• Duration of treatment with TNF-alpha antagonists \<1 year, 1-5 years, \>5 years

You may not qualify if:

• Tubercle Bacillus (TB)
• Hepatitis B, Hepatitis C
• Pregnancy and lactation
• Patients with heart failure.
• Previous or concurrent malignancies

Sponsors & Collaborators

• University of Sulaimani: lead

Study Sites (1)

Hiwa Khidhir Saaed

Sulaymaniyah, Kurdistan Region, 46001, Iraq

RECRUITING

Related Publications (5)

• Inam Illahi M, Amjad S, Alam SM, Ahmed ST, Fatima M, Shahid MA. Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis. Cureus. 2021 May 29;13(5):e15314. doi: 10.7759/cureus.15314.

  PMID: 34221763 BACKGROUND

• Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, Mariette X, Muller-Ladner U, Mysler EF, da Silva JAP, Poor G, Pope JE, Rubbert-Roth A, Ruyssen-Witrand A, Saag KG, Strangfeld A, Takeuchi T, Voshaar M, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655. Epub 2020 Jan 22.

  PMID: 31969328 BACKGROUND

• Oderda GM, Lawless GD, Wright GC, Nussbaum SR, Elder R, Kim K, Brixner DI. The potential impact of monitoring disease activity biomarkers on rheumatoid arthritis outcomes and costs. Per Med. 2018 Jul 1;15(4):291-301. doi: 10.2217/pme-2018-0001. Epub 2018 Apr 25.

  PMID: 29693487 BACKGROUND

• Abbasi M, Mousavi MJ, Jamalzehi S, Alimohammadi R, Bezvan MH, Mohammadi H, Aslani S. Strategies toward rheumatoid arthritis therapy; the old and the new. J Cell Physiol. 2019 Jul;234(7):10018-10031. doi: 10.1002/jcp.27860. Epub 2018 Dec 7.

  PMID: 30536757 BACKGROUND

• Xiao Q, Li X, Li Y, Wu Z, Xu C, Chen Z, He W. Biological drug and drug delivery-mediated immunotherapy. Acta Pharm Sin B. 2021 Apr;11(4):941-960. doi: 10.1016/j.apsb.2020.12.018. Epub 2020 Dec 31.

  PMID: 33996408 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Human Blood: CBC (complete blood count), C-reactive protein and ESR as inflammatory biomarkers, and detecting TNF-alpha and IL-6

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis; Spondylitis, Ankylosing

Interventions

Etanercept; Infliximab

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Ankylosis

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies

Study Officials

• Hiwa Saaed, PhD

  University of Sulaimani College of Pharmacy

  PRINCIPAL INVESTIGATOR

• Sana M Mohammed, BSc

  Directorate of Health, Sulaymaniyah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hiwa K Saaed, PhD

CONTACT

+9647701530462; hiwa.saaed@univsul.edu.iq

Sana M Mohammed, BSc

CONTACT

+9647702105174; sana.mohammed@univsul.edu.iq

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer and researcher at Department of Pharmacology & Toxicology, College of Pharmacy

Study Record Dates

• First Submitted: May 7, 2022
• First Posted: May 18, 2022
• Study Start: March 1, 2022
• Primary Completion: August 31, 2022
• Study Completion: October 1, 2022
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)