Systemic Medications

Reserved for moderate to severe psoriasis, systemic medications - medications that circulate throughout the body - are taken orally or given by injection or infusion. While effective, some of these medications can only be used for limited periods of time and may be combined and rotated to minimize side effects and toxicity. The systemic medications approved by the U.S. Food and Drug (FDA) Administration for the treatment of psoriasis are:

Approved to treat severe psoriasis in adults, acitretin is a retinoid (vitamin A derivative) that patients take orally. Studies show acitretin is effective in treating erythrodermic and pustular types of psoriasis. It is effective in treating psoriasis on the palms of the hands and soles of the feet. Combining acitretin with phototherapy has proven effective, especially in treating severe plaque psoriasis, and allows for lower dosage. Since acitretin does not suppress the immune system, it may be considered for patients with severe psoriasis who are HIV-positive.

Dermatologists must closely monitor their patients taking acitretin as side effects may be experienced. Regular blood tests to check lipid (fat) levels are part of this monitoring. Side effects include raised lipid levels in the blood; severe headache; liver damage; hair loss; thinning of the nails; sticky feeling to the skin; dry skin; bone spurs; and aches in the muscles, joints or bone, especially during exercise.

Oral retinoids, including acitretin, should not be used by women who are pregnant or plan to become pregnant within 3 years of discontinuing therapy due to the possibility of severe birth defects.

How it works: Acitretin normalizes skin cells’ growth, which prevents the rapid growth of and piling up of cells on the skin’s surface.


  • Effective for severe psoriasis
  • Possible treatment for HIV-positive patients
  • May be used with phototherapy to lower the dosage of acitretin


  • Many side effects possible, some significant
  • Patients must be monitored during therapy
  • Cannot be prescribed to women who plan to become pregnant within 3 years

For patients with moderate to severe psoriasis, the use of biologic agents to treat psoriasis is a much-welcomed milestone. What makes biologics unique is that these drugs pinpoint precise immune responses involved with psoriasis. Data from studies suggests that pinpointing specific immune responses produces less-toxic side effects because the entire immune system is not affected and neither are organs, such as the liver and kidneys.
Experts believe that biologics are safe overall; however, long-term research is needed to determine what side effects may occur with years of use. Scientists acknowledge that altering the immune system for years on end could lead to infections or cancer. Patients should realize that these drugs may not work for everyone.

Three biologics — alefacept, efalizumab, and etanercept — have been approved by the FDA for treating adults with moderate to severe plaque psoriasis. Etanercept also is FDA-approved for the treatment of psoriatic arthritis.

Alefacept is given by an intramuscular injection once a week for 12 weeks. Patients must visit their dermatologists for these weekly shots and get regular blood tests to check their T cell (a type of white blood cell) counts. In clinical trials, alefacept was shown to be highly effective in most patients and to have a good safety profile. Additionally, alefacept provides a long period of remission for many. In clinical trials, the average remission period for those who responded was more than 7 months; however, some remissions exceeded one year. Once remission lapses, a repeat 12-week course of therapy can be administered if 12 weeks have passed since the last shot was given. Side effects so far appear to be mild and include chills and muscle aches with the first few injections.

Efalizumab is an antibody with the ability to slip into a patient’s immune system without being detected as “foreign.” Efalizumab, unlike other systemic drugs used to treat psoriasis, provides continuous therapy and is meant for long-term use. Like alefacept, efalizumab is also given by injection once a week; however, patients can learn how to self-administer these shots. In clinical trials, patients began to see results as early as 2 weeks after beginning treatment. Once efalizumab is stopped, signs and symptoms usually reappear. Common side effects are headache, flu-like symptoms, and muscle aches with the first few injections.

Etanercept, too, is meant to provide long-term continuous therapy, and patients give themselves injections once or twice a week. The medication has been used by people with rheumatoid arthritis for more than 6 consecutive years, and data indicates that etanercept has an excellent safety profile when used for extended periods. Serious side effects remain low over time and cumulative toxicities have not been observed. The most common side effect is mild to moderate injection site reactions, such as redness, itching, pain, or swelling. These reactions usually occur during the first month and then subside.

While etanercept is meant for continuous therapy, clinical trials show that when etanercept is taken to treat psoriasis and stopped, psoriasis tends to gradually return over a three-month period. In clinical trials, withdrawal was well-tolerated and did not cause a severe psoriasis flare. Reasons to stop taking etanercept may include the patient’s need for a vaccination, desire to rotate with other treatment for psoriasis, or plans for a drug “holiday.”

How they work: Alefacept interferes with the migration as well as the activation and proliferation of T cells (a type of white blood cell). This is what gives patients relief from the signs and symptoms of psoriasis.

Efalizumab inhibits activation of the T cells and blocks T cell trafficking. This prevents the T cells from entering and causing inflammation. To gain continuous relief, efalizumab must be taken weekly. Research shows that fairly soon after stopping efalizumab, the signs and symptoms of psoriasis return.

Etanercept inhibits tumor necrosis factor (TNF)-a. It is excessive TNF-a production that can cause the increased inflammation, swelling of joints, scale, and thickness.


  • Less toxic than other systemic drugs used to treat psoriasis
  • Well tolerated
  • Alefacept shown to induce long remission in some patients
  • Efalizumab and etanercept provide continuous treatment
  • Etanercept can be safely withdrawn and resumed if needed


  • Expensive, cost may be prohibitive for some
  • Long-term effects not known
  • Not effective for all patients
  • Alefacept requires weekly visits to patient’s dermatologist

Cyclosporine is a potent immunosuppressive drug that benefits many with severe plaque psoriasis and psoriasis of the nails. It is taken in pill or liquid form. While it proves extremely effective in treating psoriasis, it is generally reserved for patients with severe cases whose condition has not responded to other therapies. Patients who respond typically show rapid improvement. Due to potential side effects, kidney function and blood pressure must be checked before the drug can be prescribed, and these need to be monitored regularly during therapy. Other side effects include increased risk of developing cancers, headache, tingling or burning sensations in the arms or legs, fatigue, abdominal upset, and musculoskeletal or joint pain.

Cyclosporine was first used to prevent rejection in organ-transplant recipients. Its effectiveness in treating psoriasis was discovered when an organ recipient who had psoriasis showed significant clearing after taking cyclosporine. This finding helped confirm that psoriasis is a dysfunction of the immune system.

The FDA recommends that cyclosporine not be used for more than one year. Patients must be carefully monitored, especially with long-term use. To help patients gain relief from the signs and symptoms of psoriasis, dermatologists may rotate cyclosporine with other systemic drugs such as methotrexate.

How it works: Cyclosporine inhibits T cell activity, which decreases the rapid growth of skin cells.


  • Highly effective in severe plaque psoriasis and psoriasis of the nails


  • Possibility of severe side effects, including kidney damage
  • Patient must be carefully monitored during therapy

One of the first chemotherapy drugs, methotrexate has been used for years to treat moderate to severe psoriasis and continues to be one of the most effective therapies for patients with erythrodermic and pustular psoriasis. Since methotrexate has potentially serious side effects, tests to check kidney and liver functions and blood are run before methotrexate is prescribed. If the tests show that the patient is a candidate for methotrexate, the patient must be carefully monitored during therapy. Patients take methotrexate either orally or by injection, usually once a week.

Patients who respond typically see an improvement within 4 to 6 weeks. After the initial clearing, the dose may be reduced or other therapies used to keep the psoriasis under control. Common side effects include nausea, fatigue, and headaches. Long-term side effects include liver damage, and patients must be closely monitored.

Methotrexate is known to cause birth defects, so pregnancy must be avoided while taking this medication. Methotrexate must not be taken during pregnancy or while trying to become pregnant. Due to multiple effects on the tissues, both men and women should stop taking methotrexate for at least 12 weeks before trying to conceive. This medication can be harmful to a nursing infant, so breast-feeding is not recommended during treatment.

Methotrexate also is not recommended for patients who have an active infection, liver disease, or a history of alcohol abuse.

How it works: Methotrexate blocks certain parts of the immune system, which decreases skin cell proliferation (rapid growth and multiplication) and suppresses inflammation.


  • Highly effective in severe psoriasis, especially erythrodermic and pustular psoriasis
  • Highly effective for psoriatic arthritis


  • Potentially serious side effects, including liver damage
  • Patients must be carefully monitored during therapy

Gribetz, C. et al. “Clearing Psoriasis: A New Era of Optimism.” Contemporary Dermatology 2003: Vol. 1, No. 1: 1-8.

More Information
Topical Preparations
Covers topical medications, moisturizers and agents that remove excess scale.

Explains the types of phototherapy used to treat psoriasis; includes information about the excimer laser.

Other Systemic Medications
Research shows these drugs, which received FDA approval for treating other conditions, may also be effective in clearing psoriasis.

AAD Consensus Statement on Psoriasis Therapy
Table lists the treatments contained in the consensus statement developed by leading dermatologists and other experts.

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