Musculoskeletal Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Infections

Rare Diseases

Arthritis

Necrosis

Arthritis, Rheumatoid

Spondylitis

Spondylarthritis

Spondylitis, Ankylosing

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Communicable Diseases

Bone Diseases

Bone Diseases, Infectious

Spinal Diseases

Axial Spondyloarthritis

Spondylarthropathies

Ankylosis

Spondylarthropathy

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Gastrointestinal Agents

All Drugs and Chemicals

Dermatologic Agents

Etanercept

Adalimumab

Infliximab

Tumor Necrosis Factor Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Immunosuppressive Agents

Immunologic Factors

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

Infliximab: Adalimumab; Etanercept;

Hiwa K Saaed, PhD

Sana M Mohammed, BSc

Hiwa Saaed, PhD

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?

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.

Human Blood:

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

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

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

The data will be presented as a Mean of the sample population.

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.

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.

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

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.

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

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.

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.

To determine how different Tumor Necrosis Factor-alpha (TNF-α) antagonist medications affected plasma (TNF-α) levels and the Disease Activity Score (DAS) in rheumatoid arthritis (RA) patients.

To determine how different Tumor Necrosis Factor-alpha (TNF-α) antagonist medications affected plasma Interleukin-6 (IL-6) levels and the Disease Activity Score (DAS) in rheumatoid arthritis (RA) patients.

University of Sulaimani

Lecturer and researcher at Department of Pharmacology & Toxicology, College of Pharmacy

Antibodies

Immunoglobulins

LY3114062 given as a single subcutaneous (SC) dose, in escalating dose cohorts starting at 2 mg.

Placebo (sodium chloride injection) given as a single SC dose.

LY3114062 SC

Placebo

LY3114062 IV

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM-5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to learn more about the safety of LY3114062 and to find out how well it is tolerated in participants with an inflammatory arthritis. The study will also investigate how the body processes the drug and how the drug affects inflammatory arthritis. The study is expected to last about 3 months.

Safety Study to Evaluate LY3114062 in Participants With Inflammatory Arthritis

A Phase 1 Single-Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of LY3114062 in Subjects With Inflammatory Arthritis

Eli Lilly and Company

Wounds and Injuries

Neoplasms

Nervous System Diseases

Syndrome

Osteoarthritis

Rupture

Fractures, Bone

Shoulder Dislocation

Contracture

Wrist Fractures

Trigger Finger Disorder

Lacerations

Dupuytren Contracture

Joint Dislocations

Elbow Fractures

Rotator Cuff Injuries

Shoulder Fractures

Shoulder Injuries

Tendon Injuries

Muscular Diseases

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Tendon Entrapment

Tendinopathy

Any form of joint replacement of the glenohumeral joint including prosthetic and excision.

Shoulder arthroplasty

Any form of joint replacement of the elbow joint including prosthetic and excision.

Elbow arthroplasty

Any form of joint replacement of joints of the hand and wrist including prosthetic and excision.

Hand and wrist arthroplasty

Open or endoscopic release of peripheral nerve entrapment - subdivided by anatomical site of compression. Specific subgroups will include carpal tunnel and cubital tunnel release.

Nerve decompression

Open or arthroscopic repair or reconstruction of tendons of the shoulder, hand and upper limb in general.

Tendon repair

Any procedure designed to increase stability of a joint, including soft tissue and bony blocking procedures.

Joint stabilisation

Any procedure performed for treatment of Dupuytren's contracture.

Excision/division/release of palmar fascia

Any internal or external fixation of upper limb fractures - analysed by anatomical site.

Surgical fixation of fractures

Any removal or release of soft tissue for treatment of stiffness, functional impairment or pain. Specific subgroups will include trigger finger release, subacromial surgery and surgery for frozen shoulder.

Soft tissue release/debridement/excision

Intra-articular injection

Dominic Furniss, DPhil

Surgery is a common treatment type for damaged joints, tendons and nerves in the upper limb where conservative measures are inappropriate or have failed. These conditions are common and result in significant levels of pain and functional disability. The investigators are conducting a broad ranging study of variation in the provision of surgical treatment and factors affecting outcomes after surgical treatment of upper limb conditions. This will be a population-based study of all patients undergoing surgical treatment funded by the National Health Service (NHS) of England over a nineteen-year period. This study will help to understand the factors associated with a poor outcome following surgery, which can be shared with patients considering treatment options. The investigators will also document current and future health service burden associated with commonly performed surgical procedures including complications and repeat operations.

The investigators will conduct time series analyses, geospatial mapping and risk-factor association studies for both access to and outcomes of surgical treatments of the upper limbs. A large cohort of pseudonymised records will be extracted from the NHS Hospital Episode Statistics Admitted Patient Care database. Suitable patients will be identified based on a match to a specified list of International Classification of Diseases (ICD-10) and Office for Population Censuses and Surveys (OPCS-4) codes. Dates and cause of death will be linked from the Office for National Statistics (ONS) by NHS Digital.

Separate analyses will be conducted for different intervention types with detailed outcomes reporting for high volume procedures. Adults will be defined as those aged 18 years or older at the time of surgery. Children will be defined as those aged less than 18 years at surgery and only included in a limited number of analyses where relevant (e.g. trigger digit).

Key analyses:

1. Baseline demographics by procedure type
2. Procedure volume incidence trends

   * Time series analysis
   * Adjusted to standard population distributions
   * Geographical mapping including adjustment for sociodemographic indices including indices of deprivation
3. Revision, reoperation and mortality rates:

   * Estimation by Kaplan Meier and actuarial life table methods
   * Life time risk calculated by the cumulative probability method
   * Cox regression adjusted for comorbidities and demographic, social and geographic factors
4. Complications, length of stay, costs:

   * Logistic and linear regression models for binary and continuous outcomes respectively
   * Adjusted for comorbidities and demographic, social and geographic factors

Where appropriate, the impact of replacing missing data will be explored with use of multiple imputation. All suitable patients will be entered into analyses to maximise statistical efficiency.

Epidemiology and Outcomes of Upper Limb Surgery: Analysis of Routine Data

The Role of Patient Factors, Surgical Factors and Hospital Factors Upon Patient Outcomes and NHS Costs in the Treatment of Upper Limb Musculoskeletal Conditions: Spatial and Iongitudinal Analysis of Routine Data

Estimated at annual increments and standardised lifetime risk

Crude and adjusted for population by age/sex

Mapped according to residence and NHS organisation boundaries

Death and infection for all. Specific adverse events dependent on procedure, e.g. periprosthetic fracture after arthroplasty surgery

Number of days - defined by time elapsed between surgery and the end of NHS spell.

Number of patients readmitted to acute NHS trust

Calculated from Healthcare Resource Group codes for index episode and related episodes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Therapeutic Response to Tumor Necrosis Factor-alpha (TNF-alpha) Antagonists in Rheumatoid Arthritis.	NCT05379049	Rheumatoid Arth... Inflammatory Ar... Ankylosing Spon...	Infliximab: Ada...	18 Years -	University of Sulaimani
Safety Study to Evaluate LY3114062 in Participants With Inflammatory Arthritis	NCT02144272	Inflammatory Ar...	LY3114062 SC Placebo LY3114062 IV	18 Years - 65 Years	Eli Lilly and Company
Therapeutic Response to Tumor Necrosis Factor-alpha (TNF-alpha) Antagonists in Rheumatoid Arthritis.	NCT05379049	Rheumatoid Arth... Inflammatory Ar... Ankylosing Spon...	Infliximab: Ada...	18 Years -	University of Sulaimani
Safety Study to Evaluate LY3114062 in Participants With Inflammatory Arthritis	NCT02144272	Inflammatory Ar...	LY3114062 SC Placebo LY3114062 IV	18 Years - 65 Years	Eli Lilly and Company
Safety Study to Evaluate LY3114062 in Participants With Inflammatory Arthritis	NCT02144272	Inflammatory Ar...	LY3114062 SC Placebo LY3114062 IV	18 Years - 65 Years	Eli Lilly and Company
Safety Study to Evaluate LY3114062 in Participants With Inflammatory Arthritis	NCT02144272	Inflammatory Ar...	LY3114062 SC Placebo LY3114062 IV	18 Years - 65 Years	Eli Lilly and Company
Epidemiology and Outcomes of Upper Limb Surgery: Analysis of Routine Data	NCT03573765	Osteoarthritis Dislocations Inflammatory Ar... Rotator Cuff Te... Shoulder Disloc... Upper Limb Nerv... Shoulder Arthro... Elbow Arthropat... Wrist Arthropat... Arthropathy Uns... Fracture, Shoul... Fracture Elbow Fracture Wrist ... Dupuytren Contr... Impingement Syn... Trigger Digit Avascular Necro...	Shoulder arthro... Elbow arthropla... Hand and wrist ... Nerve decompres... Tendon repair Joint stabilisa... Excision/divisi... Surgical fixati... Soft tissue rel... Intra-articular...	-	University of Oxford

Spots Global Cancer Trial Database for inflammatory arthritis