**4.1.1 Administration**

340 Psoriasis

Several studies evaluated the effect of alefacept in combination with other therapies, including topical agents, methotrexate, cyclosporine, acitretin, systemic retinoids, or phototherapy (Krueger et al, 2008). The results suggest that the combination of alefacept with other psoriasis therapies is efficacious and well tolerated but larger studies are needed

Alefacept is one of the safest biologic drugs for psoriasis. Clinical trials have demonstrated that it is well tolerated (Gottlieb, 2004; Krueger et al, 2002; Lebwohl et al, 2003; Roberts et al, 2010). The main concern is T lymphocyte depletion so that monitoring of CD4+ T cells is required during treatment and administration should be withheld if the CD4+ T-cell count falls below 250 cells/mL (Biogen Inc., 2003). The most common side effects are pharyngitis, headache, rhinitis, bronchitis and flu (Ellis & Krueger, 2001; Gottlieb et al, 2003; Krueger et al, 2002; Lowe et al, 2003). These infections are not severe, and there is no evidence to date to

Abatacept is a fusion protein composed of an Fc fragment of IgG1 and the extracellular domain of CTLA-4 (cytotoxic lymphocyte antigen-4) that inhibits T-cell costimulation. Abatacept is currently approved for the treatment of rheumatoid arthritis (Bristol-Myers Squibb, 2009). A phase II study has been terminated for psoriatic arthritis and it showed that

Rituximab is a chimeric monoclonal antibody that selectively binds the CD20 antigen of B cells. Rituximab is currently used in the treatment of non Hodgkin's lymphoma and rheumatoid arthritis (Genentech USA, Inc., 2011). A phase I trial is ongoing to assess the efficacy and safety of rituximab in patients with psoriatic arthritis (Swedish Medical

A third class of biologics classified as IL-12/IL-23 inhibitors has been developed for treating psoriasis. These two cytokines, mainly produced by activated dendritic cells, lead to differentiation of Th cells into the Th1 and Th17 subsets, respectively (Nestle et al, 2009). Moreover, elevated levels of IL-12 and IL-23 have been observed in psoriatic skin lesions (Yawalcar et al, 2009). Currently, ustekinumab is FDA- and EMA-approved for the treatment of chronic plaque psoriasis, whereas briakinumab, has recently had its approval application withdrawn in the US and Europe to conduct further analysis and clinical trials

Ustekinumab is a fully human monoclonal antibody that binds to the p40 subunit that is shared by IL-12 and IL-23 (Centocor Ortho Biotech, 2009). IL-12 activates natural killer and T

to confirm these results and evaluate long-term effects.

suggest a predisposition to malignancies associated with alefacept.

10 mg/kg may be an effective treatment (Mease et al, 2011).

(Centocor Ortho Biotech, 2009; Kurzeia et al, 2011).

**3.1.3 Safety** 

**3.2 Abatacept** 

**3.3 Rituximab** 

Center, 2009).

**4.1 Ustekinumab** 

**4. IL-12/IL-23 inhibitors** 

Ustekinumab is administered by subcutaneous injections at the recommended dose of 45 mg for patients who weigh ≤100 kg and 90 mg for those who weight ≥100 kg, at week 0 and then at week 4, followed by one injection every 12 weeks as maintenance treatment (Centocor Ortho Biotech, 2009). Clinical response to ustekinumab is associated with serum ustekinumab concentration and patient body weight. Two phase III clinical trials demonstrated that efficacy of the 45 and 90 mg doses of ustekinumab was similar in patients weighing ≤100 kg, while the 90 mg dose was more effective than the 45 mg dose in patients weighing >100 kg (Leonardi et al, 2008; Papp et al, 2008).
