Clinical trial NCT05379049: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Inflammatory Arthritis
Ankylosing Spondylitis
Keywords: Rheumatoid Arthritis, Cytokines
Lead sponsor: University of Sulaimani
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: Comparison of Plasma Tumor Necrosis Factor alpha (TNF-α) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.
timeFrame: Up to 12 Weeks
measure: Comparison of Plasma Interleukin-6 (IL-6) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.
timeFrame: Up to 12 Weeks
measure: Mean change of C-reactive Protein (CRP) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.
timeFrame: Up to 12 Weeks
measure: Mean change of Erythrocyte Sedimentation Rate (ESR) among different TNF alpha antagonist Therapy in Patients with Rheumatoid Arthritis.
timeFrame: Up to 12 Weeks
measure: Complete blood count (CBC)
timeFrame: Up to 12 Weeks
measure: Assessment of Disease Activity Score (DAS)
timeFrame: Up to 12 weeks
measure: Assessment of Visual Activity Score (VAS)
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: A correlation between plasma Tumor Necrosis Factor alpha (TNF-α) and disease activity and severity.
timeFrame: Up to 12 weeks
measure: A correlation between plasma Interleukin-6 (IL-6) and disease activity and severity.
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Sulaymaniyah
country: Iraq
facility: Hiwa Khidhir Saaed
state: Kurdistan Region
Study officials:
affiliation: University of Sulaimani College of Pharmacy
name: Hiwa Saaed, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Directorate of Health, Sulaymaniyah
name: Sana M Mohammed, BSc
role: PRINCIPAL_INVESTIGATOR
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