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

NCT ID: NCT06729463

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2025-03-30

Brief Summary

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

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

Conditions

Psoriasis; Psoriatic Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Humira

Intervention Type: DRUG

Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy

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.

Group Type: ACTIVE_COMPARATOR

Humira

Intervention Type: DRUG

Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy

Group C: control Group

About 10 Healthy participants and will take no medical treatment

Group Type: PLACEBO_COMPARATOR

Humira

Intervention Type: DRUG

Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy

Interventions

Humira

Assess the pharmacogenetic association between IKBKB gene polymorphism (SNPs) in psoriatic patients taking systemic biologic therapy

Intervention Type: DRUG

Other Intervention Names

Cosentyx

Eligibility Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

South Valley University

OTHER

Sponsor Role: lead

Responsible Party

Fatma Abdel-monem Mahmoud

Resident of Dermatology, Venereology and Andrology.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eisa Mohammed Hegazy, Professor

Role: STUDY_CHAIR

Dermatology, Venereology, and Andrology Department, Faculty of Medicine, South Valley University, Egypt

Locations

South Valley Hospitals

Qina, , Egypt

Countries

Egypt

Other Identifiers

Fatma Abdel-Monem

Identifier Type: -

Identifier Source: org_study_id