Genetic Variants in Egyptian Patients Receiving HCQ(Hydroxychloroquine) — HCQ  

Autoimmune Diseases Clinical Trial

Official title: Cytochrome P450 and ATP-Binding Cassette C C (ABCC) Variants in Egyptian Patients Receiving Hydroxychloroquine and Their Association With Efficacy and Toxicity

Status Not yet recruiting

Clinical Trial Summary

Hydroxychloroquine(HCQ)play major role in management of many rheumatic diseases.

Retinal toxicity from HCQ is serious side effect because even after the drug drug is discontinued, there is little if any visual recovery. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.

Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene)Which is not studied previously among Egyptian population

Clinical Trial Description

The antimalarial agent hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus.

Among rheumatic diseases, the primary role of HCQ is in the management of articular and skin manifestations of systemic lupus erythematosus (SLE) and the treatment of mild to moderately active rheumatoid arthritis (RA). As a cornerstone of SLE management, HCQ leads to reduction in the risk of disease flare as well as providing a valuable adjunct in the therapy of lupus nephritis, and is a relatively safe option for t0reatment of SLE during pregnancy,It also has been linked to the prevention thrombosis as well as a reduced risk of permanent organ damage. HCQ's beneficial effects on lipid levels and reduction in the risk of diabetes .It is a member of the "triple therapy" triad for the treatment of RA , serving as an important component of the therapeutic approach in active disease. Other less common uses for HCQ include the treatment of palindromic rheumatism, Inflammatory cutaneous disorders, and the antiphospholipid antibody syndrome because of its antithrombotic effect .

Retinal toxicity from HCQ is of serious ophthalmologic concern. Because even after the drug is discontinued, there is little if any visual recovery. Additionally, it has been shown that the retinal degeneration caused by HCQ can continue to progress. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.

The exact mechanism of HCQ and CQ toxicity remains unclear. Previously, it was hypothesized that retinal toxicity results from binding of HCQ and CQ to melanin in the retinal pigment epithelium (RPE), thus damaging the overlying photoreceptors and ultimately causing vision loss .Whether the primary effect of antimalarials occurs at the level of the RPE versus the retinal photoreceptors has been debated, however, as newer imaging technology has become available ,Early retinal toxicity is generally asymptomatic, with subtle alterations in foveal pigmentation that are often not evident on routine ophthalmologic examination. As toxicity progresses, classic "bull's eye" maculopathy, representing a ring of parafoveal RPE depigmentation sparing the central fovea, may be noted. Progression leads to increasing visual impairment, symptomatically manifesting as decreased central vision, reduced color vision, reduced night vision, reading difficulties, central scotomata, flashing lights, and increasing visual field defects.

Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration.

HCQ is metabolized to N-desethyl HCQ (DHCQ) in the liver through the N-desethylation pathway,This reaction is mediated by CYP 2D6, 3A4, 3A5, and 2C8 isoforms.

some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene) However, in 2015 ABCA4 polymorphisms proposed that could be protective agent. Which is not studied previously among Egyptian population ;

Related Conditions & MeSH terms

• Autoimmune Diseases

• NCT number: NCT03180190
• Study type: Observational [Patient Registry]
• Source: Assiut University
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 28, 2017
• Completion date: July 28, 2018