Antibodies against T-lymphocyte surface molecules
Alefacept (Amevive) is a fusion protein that blocks T-cell activation and triggers apoptosis of activated T-cells. It is given as 15mg weekly intramuscular injections. Thirty-three percent of patients reported a 75% clinical improvement in their psoriasis within 12 weeks.6 Alefacept also decreases synovial tissue T-cell count, and may have a future role in psoriatic arthritis.
It has few side effects, but patients need weekly monitoring of their CD4+ count. Ongoing studies on combining it with ultraviolet light or extending the dose to 16 weeks are showing promise.6
Antibodies against adhesion molecules
Efalizumab (Raptiva) is a monoclonal antibody that blocks T-cell activation and migration. It is self-administered by the patient as a 1 mg/kg weekly subcutaneous injection. Forty-four percent of patients achieve a 75% clinical improvement in their psoriasis by 24 weeks.
The most common side effects are headache, fever, nausea, vomiting, and myalgia. A “rebound” phenomenon after discontinuation is observed in 14%, and it may worsen psoriasis in those unresponsive to treatment.7
Other anti-TNF medications such as infliximab (Remicade), adalimumab (Humira), and onercept are still in clinical trials.
Combination therapy: Achieving goals while reducing adverse effects
Some patients require therapy with several agents to maintain adequate clearing of their psoriasis. The ideal combination therapy should lead to enhanced clinical response with reduction of adverse effects.
It is important to choose agents with synergistic effects without additive toxicities. Examples are combination of a systemic agent with topical calcipotriene, topical steroids, or with phototherapy. PUVA should be used with care for patients taking immunosuppressive agents due to risk of squamous cell carcinoma.8 A combination of 2 immunosuppressive agents is generally avoided due to risk of opportunistic infections, but has proven beneficial in a few therapy-resistant patients.9 Further clinical experience is needed for the inclusion of the new biologics in combination therapy.