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

Brief Title

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

Official Title

Evaluation of the Therapeutic Response to TNF-alpha Antagonist (Etanercept, Infliximab, Adalimumab) in Patients With Rheumatoid Arthritis; Using Plasma TNF-alpha as a Competent Biomarker. Single Center Study in Sulaymaniyah/ Iraq

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?
    

Detailed Description

      Rheumatologists in Iraq, including those in the Kurdistan Region, rely on the European League
      Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) guidelines and
      publications due to a lack of evidence-based national guidelines.

      Several studies found that targeting TNF-alpha in the early stages of RA and evaluating serum
      TNF- levels, in combination with DAS28's assessment of disease clinical activity to track
      disease progression could result be advantageous for patients on anti-TNF medication in the
      future.

      Objectives: The current research focuses on identifying the efficacy of three TNF-alpha
      antagonists (Etanercept, Infliximab, and Adalimumab) used currently in Sulaymaniyah
      Hospitals.

      Methodology, an observational open-label study of ~60-80 adult patients with active RA from
      both genders that are registered at Rehabilitation and Rheumatology Center in Sulaymaniyah
      City who have been treated with biological agents (Etanercept, Infliximab, Adalimumab),
      regardless of disease activity and concomitant treatments.

      Baseline data will be collected during the first visit and patients will be followed up
      during the study at regular intervals.

      The study includes data of patients after filling the patient consent form, and are willingly
      giving their demographic data such as; Age, Sex, and Race (ethnic group). and answer the
      questions of multidimensional health assessment. Also measuring patients' weight at each
      visit, The clinical assessment of the patients is based on DAS28 (Disease Activity Score) by
      using ESR(Erythrocyte Sedimentation Rate), and VAS (Visual analogue score).

      The laboratory data or the biomarkers at each visit include; CBC (complete blood count),
      C-reactive protein and ESR as inflammatory biomarkers, and detecting TNF-alpha and IL-6 to
      indicate the efficacy of the treatment and better choice of the treatment.

      As for the statistical analysis plan, the Software SPSS (version 27) will be used.

      Demographic and nominal results will be reported in percentages and frequencies.

      Numerical results will be reported as the mean and standard deviation in cases of normal
      distribution, and as the median and interquartile range (IQR) in cases of skewed
      distribution.

      The continuous variables CRP, TNF, IL-6 and the change over time, will be analyzed using
      linear mixed models for repeated measures. The chi-squared test will be used for dichotomous
      variables.
    


Study Type

Observational


Primary Outcome

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

Secondary Outcome

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

Condition

Rheumatoid Arthritis

Intervention

Infliximab: Adalimumab; Etanercept;


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

80

Start Date

March 1, 2022

Completion Date

October 1, 2022

Primary Completion Date

August 31, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  Tubercle Bacillus (TB)

          -  Hepatitis B, Hepatitis C

          -  Pregnancy and lactation

          -  Patients with heart failure.

          -  Previous or concurrent malignancies
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Hiwa Saaed, PhD, +9647701530462, [email protected]

Location Countries

Iraq

Location Countries

Iraq

Administrative Informations


NCT ID

NCT05379049

Organization ID

UoS


Responsible Party

Principal Investigator

Study Sponsor

University of Sulaimani


Study Sponsor

Hiwa Saaed, PhD, Principal Investigator, University of Sulaimani College of Pharmacy


Verification Date

May 2022