tnf a inhibitors by: mohammed alsaidan. biologics biologic agents are proteins that can be extracted...

TNF a inhibitors

BY: MOHAMMED ALSAIDAN

Biologics

Biologic agents are proteins that can be extracted from animal tissue or produced by recombinant DNA technology and possess pharmacologic activity

TNF a

• TNF a is a major cytokine produced by Th1 cells, APC and keratinocytes

• TNF a in the lesion and serum level correlate with severity of psoriasis

• TNF potentiate Th1 response, up-regulate intracellular and vascular adhesion, cause keratinocytes proliferation and potentiate other cytokines

TNF a adverse effects

• Viral, bacterial and mycobacterial infections (less with etanercept) ( HCV ?!)

• Neurologic disease • Heart disease • Drug induced lupus-like syndrome• Hepatic disease (infliximab)• Lymphoma• Melanoma and non-melanoma skin cancer• Haematologic disease

Monitoring

• PPD +/- CXR• CBC , U/E , LFT• Hepatitis panel • ANA

Injections

• Should not be frozen• Stable for 14 days• Allow for return to room temp before injection• Site : thigh, abdomen, upper arms• Rotate injection site

Indications for Etanercept

• FDA approved for psoriasis and psoriatic arthritis

• Off label dermatologic uses: • Neutrophilic dermatoses: PG, behcet , aphthous stomatitis• Bullous dermatoses: PV, CP• Sarcoidosis • DM, relapsing polychondritis • GVHD, hidradenitis suppurativa, multicentric reticulohistiocytosis

T cell activation inhibitors

IL 12/23 blockage (Ustekinumab)

• The p40 subunit of IL 12 is overexpressed in psoriasis• It is a human monoclonal antibody• Superior to etenercept • Given 45 mg S.C at weeks: 0,4, 16, 28

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