Biotechnological Treatments for Psoriasis
Biologic drugs represent one of the greatest medical innovations of the last few years. Their success is due to their highly selective action that allows most times a great and rapid therapeutic efficacy and low side effects compared to traditional “chemical” treatments. Currently produced biologics are monoclonal antibodies, cytokines (interferons or interleukins), fusion proteins and tissue growth factors.
All these products have the great advantage to act in a selective manner, at different levels and with different methods of actions on the immune processes responsible for the onset of psoriasis. It is a renowned fact that psoriasis involves skin cells such as keratocynes, and the blood cells in charge of defending the immune system, e.g. Lymphocytes T.
The altered “physiological” dialogue between these two kinds of cells brings an imbalance in the synthesis of the lymphocyte T products, with an enormous production of a series of cellular interaction molecules, leading to erythema and scale formation.
The most studied molecules are: Etanercept, Efalizumab*, Infliximab, Adalimumab, Alefacept and Ustekinumab.
Etanercept (Enbrel) is a fusion protein obtained through recombinant DNA techniques of the p75 human receptor of the TNF-alpha factor with the Fc fraction of IgG1 human immunoglobulin. The protein acts as a soluble receptor for the TNF-alpha factor and has a stronger binding affinity for TNF-alpha than those of other soluble receptors. The drug is administered via subcutaneous injections. Etanercept has been registered in EMEA (European Medicines Evaluation Agency) and is indicated for psoriasis, psoriatic arthritis and rheumatoid arthritis. It has been inserted in the Italian NHS list of reimbursable drugs via AIFA (Italian Drug Agency) Decision of 25/06/2005 for the treatment of moderate to severe plaque psoriasis in cases of resistance or failure of conventional systemic treatments.
Efalizumab* (Raptiva) is a drug belonging to the anti-CD11 category. It is a recombinant humanised monoclonal antibody that specifically binds an important lymphocyte T adhesion molecule, fundamental for the three key processes responsible for generating psoriasis, namely the link of lymphocytes to other cells, blood migration towards the derma and the activation of T cells leading to the release of inflammatory cytokines and the proliferation of β-keratins. The drug is registered in EMEA; it is indicated for the treatment of psoriasis and administered via subcutaneous injections. Also this drug is reimbursed by the Italian NHS due to AIFA’s aforementioned decision.
* The Committe fof Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has analysed the currently available data regarding the safety of Raptiva (efalizumab) and has stated that according to our current knowledge, the benefits of Raptiva are lower than the associated risks. Therefore, EMEA has recommended the suspension of the product.
Infliximab (Ramicade) is a monoclonal antibody, inhibiting the activity of and binding to the Tumor Necrosis Factor (TNF-alpha) with a high specificity and affinity both in soluble and in trans-membrane form. TNF-alpha is pro-inflammatory cytokine highly present in psoriatic lesions and in the joint synovia of patients suffering from psoriatic arthritis. There is great evidence of a correlation between severe skin pathology and the hyperproliferation of erythema and scales, respectively. The drug is administered intravenously and is indicated for psoriasis and psoriatic arthritis. The drug is indicated for the treatment of psoriasis and psoriatic arthritis. AIFA’s decision n.87/2006 established this drug as reimbursed by the Italian NHS; its therapeutic use is for the treatment of moderate to severe plaque psoriasis in cases of resistance or failure of conventional systemic treatments.
Adalimumab (Humira) is a monoclonal antibody targeting the TNF-alpha. The drug is administered subcutaneously in a liquid preparation dose of 40 mg a week. As all anti TNF-alpha, the drug has a highly selective action, i.e. it is able to act exclusively on the activity of the molecule without interfering on the other systems of the body. The drug is indicated for the treatment of psoriatic arthritis and now also for psoriasis.
Alefacet is a LFA-3/IgG1 human fusion protein that acts by blocking the interaction among the cells containing the antigene and the lymphocytes T. Approved by FDA (Food and Drug Administration), the drug is currently the subject of specific European studies/trials.
Ustekinumab (Stelara) is an entirely human IgG1k monoclonal antibody that binds with high affinity and specificity the p40 protein subunit of interleukins IL-12 and IL-23, human cytokines, inhibiting the bond between these cytokines and the specific IL-12Rbeta1 receptor expressed on the surface of immune cells. The drug is indicated for psoriasis and administered subcutaneously every 4 weeks at first and then every 12 weeks. AIFA’s decision of 29 December 2009 established this drug as reimbursed by the Italian NHS.
The "Psocare" project foresees the monitoring in the reference centres indicated in each Italian region of the Biologics registered by EMEA in order to verify their tolerability, efficiency and long-term efficacy.
