IKBKB Gene Polymorphism (Single Nucleotide Polymorphism) (SNP) in Psoriatic and Psoriatic Arthritis Patients

IKBKB Gene Polymorphism (Single Nucleotide Polymorphism) (SNP) in Psoriatic and Psoriatic Arthritis Patients and Its Relation With Response to Systemic Biologic Therapy

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. It impairs patients' quality of life enormously.

Psoriasis refers to a persistent inflammatory illness of the skin and joints. It also impacts roughly 2%-3% of the inhabitants of the universe

Study Overview

• Status: Completed
• Conditions: Psoriasis; Psoriatic Arthritis
• Intervention / Treatment: Drug: Humira

Detailed Description

The exact aetiopathogenesis of psoriasis is not completely explained. Pathological mechanism involves skin inflammation and hyperproliferation of keratinocytes induced innate and adaptive immune cells. Genetic, immunological and environmental factors are considered the most important aetiologies.

Psoriatic arthritis, which is characterized by dactylitis and enthesis, is closely associated with psoriasis. Up to 30-40% of patients with psoriasis will develop PsA, with an average of 10 years between psoriasis and PsA . The overlapping of genetic variations and inflammatory mediators involved in psoriasis and PsA implies a common pathogenic mechanism between the two diseases.

Psoriasis is a chronic relapsing disease, which often necessitates a long-term therapy. Mild to moderate psoriasis can be treated topically with a combination of glucocorticoids, vitamin D analogues, and phototherapy. Moderate to severe psoriasis often requires systemic treatment. The presence of comorbidities such as psoriasis arthritis is also highly relevant in treatment selection.

Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor.

The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles.

Specifically, inhibitors to tumour necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-13 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis.

The NF-κB pathway would play an important role in psoriasis. In this way, the NF-κB is regarded as a mediator between immunity and the keratinocyte alteration characteristic of psoriasis .

This role is also supported by the fact that the blockade of the NF-κB binding sites would reduce the expression of several proinflammatory cytokines implicated in psoriasis. The transcriptional activity of NF-κB is regulated by several cytoplasmic inhibitors. Among these nuclear inhibitors, IκBKB (encoded by NFKBIZ) would play a prominent role in the pathogenesis of psoriasis.

IκBKB(Inhibitor of nuclear factor-kappa B subunit ζ ) is induced by several proinflammatory molecules. In particular, its expression is regulated by IL-17A and might contribute to the activation of Th17-mediated pathways. Therefore, IκBζ( IκBKB) plays an important role in the pathogenesis of psoriatic disease through IL-17-mediated mechanisms.

Recently, genome-wide association studies (GWAS) have found a significant association between psoriasis and single-nucleotide polymorphisms (SNPs) within NFKB1, NFKBIA, and NFKBIZ

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Qinā, Egypt
    • South Valley Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients between the ages of 16 and 60 years proved having psoriasis diagnosed clinically for at least 6 months and who have a severity grade of moderate to severe, defined as a Psoriasis Area and Severity Index (PASI) score greater than 10, and involvement of greater than 10% of the body surface area (BSA) with or without psoriatic arthritis

Exclusion Criteria:

• Patient receiving immune suppressive drugs.
• Patients having malignancy.
• Pregnant or lactating female.
• Patients having liver disease ( Hepatitis)
• Patients having comorbid and/or uncontrolled renal, cardiac, vascular, and hepatic diseases or symptoms.
• Active infection or human immunodeficiency virus (HIV)
• Tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Humira Group; About 20 patients suffering from psoriasis disease and they will take Humira vials about 40 mg every two weeks by subcutaneous injection for 3 months	Drug: Humira; Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy; Other Names: Cosentyx
Active Comparator: Group B: Cosentyx Group; About 20 patients suffering from severe psoriasis will take Cosentyx vials by intravenous infusion as : 1-Loading dose about(300 mg) then decreasing the dose to be 150 mg every month for 3 months.	Drug: Humira; Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy; Other Names: Cosentyx
Placebo Comparator: Group C: control Group; About 10 Healthy participants and will take no medical treatment	Drug: Humira; Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy; Other Names: Cosentyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment of the Psoriasis disease	Evaluation the clinical efficacy of biological therapy in patients of psoriasis and assessing the relation between the drug response and IKBKB mutation	3 months

Collaborators and Investigators

• Sponsor: South Valley University
• Investigators: Study Chair: Eisa Mohammed Hegazy, Professor, Dermatology, Venereology, and Andrology Department, Faculty of Medicine, South Valley University, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 8, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Joint Diseases; Spinal Diseases; Spondylarthropathies; Skin Diseases, Papulosquamous; Skin Diseases; Spondylarthritis; Spondylitis; Arthritis; Psoriasis; Arthritis, Psoriatic; Tumor Necrosis Factor Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: Fatma Abdel-Monem

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No