Medical Health Encyclopedia

Drug and Food Interactions. Cyclosporine interacts with numerous drugs--both prescription and over-the-counter preparations--and also grapefruit and grapefruit juice.

Second- and Third-Line Systemic Agents

Second- or third-line agents are used alone or sometimes in combination with first-line systemic drugs if those medications fail. Most are investigative and are generally less safe than first-line agents.

Sulfasalazine. Sulfasalazine (Azulfidine) sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only agents proven to help patients with psoriatic arthritis. Many people, however, stop taking the drug because of common side effects that include headaches, gastrointestinal complaints, and rash. Benefits, if any, should be apparent in four to six weeks.

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Macrolides. Macrolides are agents that fight bacteria and also have immunosuppressant properties. (Their actions are similar to those of cyclosporine.) Some macrolides being studied for psoriasis include tacrolimus (Prograf), pimecrolium, and sirolimus. In one study, for example, tacrolimus showed an 83% reduction in symptoms in patients with psoriasis who used the drug. Studies have been limited, however. Side effects of these agents are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and so have fewer side effects. (Some macrolides are also being studied as topical treatments.)

Biologic Response Modifiers

Biologic response modifiers, sometimes called "biologics," belong to a new class of drugs that are considered the most exciting development in psoriasis treatment. Four such drugs have been approved since 2003. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not damage the entire immune system the way that general immunosuppressants do.

T-Cell Blockers. In psoriasis, and other inflammatory diseases, T cells (immune cells) become overactive. Drugs that block T cell activation can help prevent psoriasis flare-ups and reduce symptoms.

• Alefacept (Amevive) received FDA approval in January 2003 for treatment of moderate-to-severe plaque psoriasis. It was the first biologic drug approved for psoriasis. Studies suggest that the drug produces 50 – 75% improvement in symptoms. Alefacept is given in a doctor’s office or clinic. Patients receive weekly intramuscular injections for 12 weeks. Blood tests are also done weekly to make sure that T cell levels do not drop too low. Alefacept’s side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
• Efalizumab (Raptiva) was FDA-approved in December 2003 for treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 –75% improvement in symptoms within four to six weeks of starting the drug. Unlike alefacept, patients can inject efalizumab by themselves at home. Weekly subcutaneous (under the skin) injections are given for 12 weeks. Recent clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients experience flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia, (due to red blood cell destruction), and antibiotic-resistant infections.

Tumor Necrosis Factor (TNF) Blockers. Activated T cells release chemical messengers that cause an inflammatory response. This inflammatory response can increase skin cells in psoriasis and can cause joint pain in psoriatic arthritis. The TNF blockers used to treat psoriasis target the chemical messenger TNF-alpha.

• Etanercept (Enbrel) was approved in 2002 for treatment of psoriatic arthritis, and in 2004 for treatment of moderate-to-severe plaque psoriasis. In 2005, etanercept was also approved to improve physical function in patients with psoriatic arthritis. The drug is given either alone or in combination with methotrexate. Patients inject themselves under the skin, once or twice a week for 12 weeks. Etanercept can cause infections and should not be used by patients with weakened immune systems or heart failure. TNF-blockers have also been associated with increased risk of developing lymphomas (a type of cancer).
• Infliximab (Remicade) was approved in 2005 for treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first six weeks of treatment. After this initial treatment period, patients receive an infusion every eight weeks. The infusions take two hours and are given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug.
• Adalimumab (Humira) is another TNF-blocker. It is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and is a powerful anti-inflammatory agent. It is proving to be active against psoriatic arthritis. Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury.

Interleukins. Interleukins are other powerful inflammatory agents of the immune system. Interleukins being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. For example, in a 2003 study, 75% of patients with severe psoriasis who were treated with interleukin-4 (rhuIL-4) experienced improvement rates of more than 68%.