**9.4.4.2 T cell inhibitors**

**Alefacept** (Amevive®) is a human recombinant fusion protein composed of LFA-3 with the Fc portion of human IgG. In psoriasis, the inflammatory response is amplified when LFA-3 molecule-containing antigen presenting cells bind to the CD2+ receptor of T cells, the result being T cell activation and the release of proinflammatory cytokines. Alefacept binds to the CD2+ receptor of T cells via its LFA-3, thus blocking this interaction with antigen-presenting cells. Furthermore, alefacept triggers apoptosis of memory T cells. Through these two mechanisms, alefacept decreases the number of pathogenic T cells in psoriasis (Weinberg, 2003, Lawry 2007).

Alefacet is usually given in a dose of 15 mg per week for a period of 12 weeks; intravenous administration is also possible. At baseline, the CD4+ T cells should be monitored and then every 2 weeks. A CD4+ count below 250/µl should prompt to withhold the treatment until it has recovered. As alefacept has proven to be very safe the 2-weekly CD4 cell count may be delayed. Side effects include pruritus, headache, fatigue, nausea, viral upper respiratory infections, and arthralgias. Malignancy and serious infections do not appear to occur more frequently with alefacept use (Scheinfeld, 2005).

There are few studies and reports on alefacept use in nail psoriasis (Körver et al, 2006, Parrish et al, 2006). In moderate nail psoriasis, 2 patients improved, 2 remained unchanged and one worsened (Körver et al, 2006).

**Efalizumab** (Raptiva®) is a humanized monoclonal antibody against the CD11 portion of the LFA-1 molecule on lymphocytes. LFA-1 usually binds to intercellular adhesion molecule and promotes lymphocyte migration. The binding of efalizumab to CD11a cells is reversible and does not deplete T cells, but it prevents them from migrating into the skin (Weinberg, 2003). It has shown efficacy in the treatment of cutaneous and nail psoriasis but the European Medicines Agency (EMA) recommended its suspension of the marketing authorization after the occurrence of cases of progressive multifocal leukoencephalopathy (19 February 2009 Doc. Ref. EMEA/CHMP/20857/2009).

#### **Cytokine inhibitors**

**Ustekinumab** (Stelara®) is a new human IgG1k monoclonal antibody to the p40 epitope common to both IL-12 and IL-23. It blocks the differentiation and expansion of T helper cells 1 and 17 (Leonardi et al, 2008). It is indicated in moderate-to-severe psoriasis resistant to other therapies or with contraindications or intolerance to other systemic treatments. Ustekinumab is given in a dose of 45 mg for individuals under 100 kg body weight. In a patient who had earlier etanercept and failed to respond later ustekinumab was given and a

Serious adverse events of all TNF- inhibitors include the development of viral, bacterial, mycobacterial, and fungal infections (Lowther et al, 2007), reactivation of tuberculosis, hepatitis B and C, allergic infusion reactions, malignancies, autoantibody formation with lupus erythematosus, pancytopenia and aplastic anaemia, neurological disorders and worsening of congestive heart failure (Smolen and Emery, 2011). Experience in pregnancy is lacking. Further, infliximab comes with an information what to look for before starting a treatment. Paradoxical sarcoidosis while on anti-TNF- treatment was also reported

**Alefacept** (Amevive®) is a human recombinant fusion protein composed of LFA-3 with the Fc portion of human IgG. In psoriasis, the inflammatory response is amplified when LFA-3 molecule-containing antigen presenting cells bind to the CD2+ receptor of T cells, the result being T cell activation and the release of proinflammatory cytokines. Alefacept binds to the CD2+ receptor of T cells via its LFA-3, thus blocking this interaction with antigen-presenting cells. Furthermore, alefacept triggers apoptosis of memory T cells. Through these two mechanisms, alefacept decreases the number of pathogenic T cells in psoriasis (Weinberg,

Alefacet is usually given in a dose of 15 mg per week for a period of 12 weeks; intravenous administration is also possible. At baseline, the CD4+ T cells should be monitored and then every 2 weeks. A CD4+ count below 250/µl should prompt to withhold the treatment until it has recovered. As alefacept has proven to be very safe the 2-weekly CD4 cell count may be delayed. Side effects include pruritus, headache, fatigue, nausea, viral upper respiratory infections, and arthralgias. Malignancy and serious infections do not appear to occur more

There are few studies and reports on alefacept use in nail psoriasis (Körver et al, 2006, Parrish et al, 2006). In moderate nail psoriasis, 2 patients improved, 2 remained unchanged

**Efalizumab** (Raptiva®) is a humanized monoclonal antibody against the CD11 portion of the LFA-1 molecule on lymphocytes. LFA-1 usually binds to intercellular adhesion molecule and promotes lymphocyte migration. The binding of efalizumab to CD11a cells is reversible and does not deplete T cells, but it prevents them from migrating into the skin (Weinberg, 2003). It has shown efficacy in the treatment of cutaneous and nail psoriasis but the European Medicines Agency (EMA) recommended its suspension of the marketing authorization after the occurrence of cases of progressive multifocal leukoencephalopathy

**Ustekinumab** (Stelara®) is a new human IgG1k monoclonal antibody to the p40 epitope common to both IL-12 and IL-23. It blocks the differentiation and expansion of T helper cells 1 and 17 (Leonardi et al, 2008). It is indicated in moderate-to-severe psoriasis resistant to other therapies or with contraindications or intolerance to other systemic treatments. Ustekinumab is given in a dose of 45 mg for individuals under 100 kg body weight. In a patient who had earlier etanercept and failed to respond later ustekinumab was given and a

(Pine et al, 2010)

2003, Lawry 2007).

**Cytokine inhibitors** 

frequently with alefacept use (Scheinfeld, 2005).

(19 February 2009 Doc. Ref. EMEA/CHMP/20857/2009).

and one worsened (Körver et al, 2006).

**9.4.4.2 T cell inhibitors** 

marked improvement of his nail signs was noted after 4 weeks. A complete cure was achieved 4 weeks later after the second injection (Rallis et al, 2010).

**Tocilizumab** (Actemra®) is an IL-6 receptor inhibitor. No reports on nail psoriasis treatment have been published hitherto.

#### **T cell inhibitors**

**Abatacept** (Orencia®) is a soluble chimeric protein consisting of the extracellular domain of human CD152 linked to the modified Fc portion of human IgG1. By binding to B7-1 (CD80) and B7-2 (CD86) molecules on antigen presenting cells, CTLA4Ig blocks the CD28-mediated costimulatory signal for T cell activation. Success with abatacept has been noted in psoriasis. Abatacept was administered to two patients with refractory psoriasis and psoriatic arthritis after the patients had failed all conventional treatment methods. Both patients experienced very brief improvement in disease (Altmeyer et al, 2011).

**Rituximab,** a B cell depleting chimeric antibody has no place in the treatment of nail psoriasis.

#### **9.5 Combined treatments**

In clinical routine, different treatments are often combined as one is either insufficient or too slow. The combination should always consist of drugs with different mechanisms of action. In contrast to skin psoriasis, there are almost no studies on the effect of combination therapy on nail psoriasis (Jiaravuthisan et al 2007). A single-blinded study on 54 patients with nail psoriasis examined the effects of cyclosporine monotherapy versus cyclosporine systemically plus calcipotiriol cream topically (Feliciani et al 2004). The cyclosporine dose was 3.5 to 4.5 mg/d, calcipotriol was applied twice daily. After 3 months, the combined treatment showed significant improvement of pitting, subungual hyperkeratosis and onycholysis in 79%, whereas the cyclosporine monotherapy group showed 48% marked improvement. Six months after treatment, the cyclosporine monotherapy group showed a relapse rate of 52.9% (9/17), whereas only 37% (10/27) of patients in the combined therapy group had any signs of recurrence.
