**8. Conclusion**

256 Psoriasis

patient), gastric ulcer haemorrhage/abdominal pain/back pain (1 patient) and basal cell carcinoma (1 patient) respectively (A. Gottlieb et al., 2009). Two serious infections occurred during the placebo-controlled phase of the two large phase III trials: one case of cellulitis and one case of herpes zoster (both in the ustekinumab 90-mg group) (Ding et al., 2008;

During the placebo-controlled phase of the Phoenix 2 study, a squamous cell carcinoma in a patient in the placebo group and a basal cell carcinoma in a patient in the ustekinumab 90 mg group were observed (Ding et al., 2008). Comparing patients on maintenance therapy with patients randomized to the withdrawal group in Phoenix 1 study did not reveal an

(30)

(30)

**of patients)**

B 200 mg x 1 (30) B 100 mg eow (3) B 200 mg x 4 (30) B 200 mg eow

B 200 mg weekly

Placebo (30)

U 45 mg (255) U 90 mg (256) Placebo (255

U 45 mg (409) U 90 mg (411) Placebo (410)

U 45 mg (209) U 90 mg (347) E 2 X 50 mg (347)

B = Briakinumab; E = Etanercept; U = Ustekinumab; RDBPC = Randomized Double-Blind Placebo

**Major Results**

PASI 75 at week 12: 63 PASI 75 at week 12: 93 PASI 75 at week 12: 90 PASI 75 at week 12: 93 PASI 75 at week 12: 90 PASI 75 at week 12: 1

PASI 75 at week 12: 67.1 PASI 75 at week 12: 66.4 PASI 75 at week 12: 3.1

PASI 75 at week 12: 66.7 PASI 75 at week 12: 75.7 PASI 75 at week 12: 3.7

PASI 75 at week 12: 67.5 PASI 75 at week 12: 73.8 PASI 75 at week 12: 56.8 **Reference** 

Kimball *et al*.,

*Arch Dermatol*  144: 200–207.

Leonardi *et al*.,

Papp *et al*., 2008 *Lancet* 371: 1675–1684.

Griffiths *et al*.,

*N Engl J Med*. 362: 118-128

2010

2008 *Lancet* 371: 1665 -1674.

2008

increased infection rate between the two groups (Ortonne et al., 2007).

RDBPC

**Therapy Disease Trial Type Treatment (n°** 

Psoriasis RDBPC

Psoriasis RDBPC

Psoriasis RDBPC

Table 4. Efficacy of anti- IL-12/IL-23 in the psoriasis cure

Briakinumab Psoriasis 12-week

Ortonne et al., 2007).

Ustekinumab PHOENIX 1

Ustekinumab PHOENIX 2

Ustekinumab ACCEPT

Controlled Trial

Based on a large series of studies, that we discuss in the different paragraphs, current evidence indicates the importance of T cells during psoriasis pathogenesis and demonstre that T cell expansion precedes the development of typical psoriatic changes; the more reasonable conclusion is that psoriasis is the outcome of an inappropriate T cell-based activation event, together with a defect in KCs, whose combination results in the full psoriatic phenotype.

Once recognized the primary role of T cells in psoriasis pathogenesis, several biological therapies have been developed and proposed to counteract immune T response. These treatments consist in blocking the actions of several T cell cytokines that play a key role in sustain the pathogenesis of early and late events of psoriasis, e.g. anti-IL23 and anti-TNF-.

So far, considering published data from the clinical trials, the new biological agents have been shown to be efficient treatment options for patients suffering from psoriasis and the major comorbidities disease-associated, primarily PsA.

These new biological agents seem to have proven a good risk/benefit ratio. As psoriasis is considered a life-long disease and no causal therapy for the disease is yet available, longterm studies on safe and efficacious treatments are needed and are of major importance.

Taking into account the possibility that uncommon adverse events or events occurring during long-term exposure to these drugs might emerge in the future (e.g. the development of progressive multifocal leukoencephalopathy in long-term patients treated with efalizumab), vigilant and careful post-marketing surveillance in patients treated with biological agents is strongly recommended.
