Systemic treatment uses various medications that affect the whole body, not just the skin. Many systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer.
Systemic treatments for psoriasis may be taken by mouth, subcutaneous injection, or IV infusion. The medicines can have significant side effects and are generally reserved for moderate to severe psoriasis.
Systemic medications approved for treating psoriasis include:
- Biologic response modifiers
Physicians sometimes prescribe medications off-label. The medications below are not specifically approved for psoriasis, but they are sometimes effective. The following drugs are FDA approved for other conditions, such as acne or cancer, but may sometimes be prescribed for psoriasis:
- Hydrea (hydroxyurea)
As with all medications for psoriasis, people should use the lowest strength medication first. The primary treatment is called a first-line treatment, the next is known as a second-line treatment, and so on. Combinations of medications are often used.
Several biologic agents to treat psoriasis are available or under study, including oral medications, monoclonal antibodies, anti-interleukin antibodies.
Methotrexate is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first-line, or primary, systemic drug used to treat adults with severe psoriasis. It has been used for psoriasis since the 1950s.
The drug is taken once weekly by mouth or subcutaneous injection.
Many people are able to tolerate methotrexate with few side effects. Possible side effects include:
- Anemia, usually causing no noticeable symptoms
- Mild and slow hair loss that is reversible when the medication is stopped
- Increased likelihood of becoming sunburned
- Mouth sores
- Nausea, usually mild and improves over time
- Possible muscle aches
- Vomiting (rare)
Many of these side effects are due to folic acid deficiency. People should ask their doctor if they should take folic acid supplements (generally recommended at 1 mg daily on the days not taking the methotrexate).
More serious, but relatively uncommon side effects include:
- Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. People with active infections should avoid this drug.
- Infertility, miscarriage, and birth defects. This drug should not be used during pregnancy, because it can cause miscarriages or birth defects. It may harm fertility in men.
- Kidney damage.
- Liver damage, most commonly in people with existing liver problems. Regular monitoring for liver toxicity includes blood tests and sometimes liver biopsies. People who are properly monitored rarely have any permanent liver damage.
- Cough and shortness of breath. Risk factors for these side effects include diabetes, existing lung problems, protein in the urine, and the use of rheumatoid arthritis drugs of a type called DMARD.
- Severe anemia. Folic acid supplements can offset this effect.
- Toxic effects on bone marrow. This can cause reduced blood cell production.
Despite methotrexate's side effects, some experts view it as the best therapy for widespread plaque psoriasis. It may also be effective for some people with generalized erythrodermic and pustular psoriasis.
Methotrexate appears to be effective in children, but more safety research is needed.
Many drugs interact with methotrexate, occasionally with harmful results. For example, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.
Taking nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen at the same time as methotrexate may change the blood levels of methotrexate. Always talk with your doctor before taking these or any other medications in combinations.
People Who Should Avoid Methotrexate
Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before the actual pregnancy. Methotrexate may also cause temporary impairment of fertility in men. People with Hepatitis B should not take methotrexate.
People with the following conditions are unlikely to be given methotrexate:
- Anemia or other blood abnormalities
- Kidney problems
- Liver problems (including hepatitis)
- Peptic ulcers
- Suppressed immune system
Oral retinoids are vitamin A-related medications taken by mouth. This group of medicines is also a first-line treatment for adults with severe psoriasis. Oral retinoids used for psoriasis include acitretin and isotretinoin.
Acitretin (Soriatane) is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic types. It is also effective in a low-dose formulation for symptoms of nail psoriasis. When used alone, it is much less effective against more common forms of psoriasis, such as plaque or guttate psoriasis. However, when combined with UVB phototherapy it can markedly improve the response, even in people with these forms of psoriasis. It is not effective for psoriatic arthritis.
Isotretinoin (Accutane), more commonly used to treat acne and not FDA-approved for psoriasis, is far less potent than acitretin, but it may still be effective against pustular psoriasis. The drug may also be effective with phototherapy.
Oral retinoids help control cell reproduction and have anti-inflammatory properties. They may even improve arthritis that accompanies psoriasis.
Acitretin may work best when combined with other treatments, usually topical drugs and especially phototherapy. Combination therapy allows lower doses of oral retinoids to be used, which diminishes many skin and mucus membrane side effects. Acitretin combined with phototherapy has some of the greatest success rates of any treatment.
All retinoids have the same potentially serious toxicities, as do high doses of vitamin A. Side effects include:
- Bone and joint pain
- Depression and possible suicide risk (with isotretinoin)
- Eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision
- Increased bone growth, particularly in the ankles, pelvic area, and knees
- Increased triglyceride levels
- Liver damage
- Nail problems
- Skin and mucus membrane problems, including dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles
In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. People experiencing these symptoms should call a doctor immediately and stop taking the drug. There is increased risk for this with concomitant use of tetracycline antibiotics.
Oral retinoids should not be taken by women of child-bearing age, as acitretin can stay in the body for up to 3 years and lead to severe birth defects.
Despite these side effects, oral retinoids remain among the safest whole-body therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects. Certain cholesterol-lowering drugs, including gemfibrozil (Lopid) and atorvastatin (Lipitor), may help control triglyceride levels.
Maintenance doses should be as low as possible and should be taken every second or third day.
Oral Retinoids and Pregnancy
Taking retinoids during pregnancy significantly increases the risk for severe birth defects in the unborn child. Pregnant or nursing women, or those planning to become pregnant, should not use these drugs. Women of childbearing age who take retinoids should have regular pregnancy tests.
- Acitretin is an oral retinoid used typically for first line-therapy of chronic palmoplantar or pustular psoriasis. It may be used in combination with other therapies to treat plaque psoriasis. Acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential to cause birth defects during that time. Be cautious about cooking products and over-the-counter preparations, such as cough syrup, which may contain alcohol.
- Women who are pregnant or who plan to become pregnant should not use isotretinoin. Everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE, which helps to ensure that no woman starts retinoid therapy while pregnant or trying to get pregnant.
Cyclosporine blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first-line, or primary, systemic drug used to treat adults with severe psoriasis, von Zumbusch pustular psoriasis, or erythrodermic psoriasis. Cyclosporine often clears psoriasis in many patients within 8 to 12 weeks.
Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for people who do not respond to phototherapy or less potent systemic medications (such as, methotrexate or acitretin).
Common and temporary side effects include:
- Excessive growth of body hair
- Joint pain
More serious complications may include:
- Kidney damage.
- High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, because other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
- High cholesterol and lipid levels.
- High levels of calcium and low levels of magnesium.
- Increased risk for infections.
- Liver problems.
- Lymphomas (cancers of the lymphatic system).
- Skin cancers (People who take cyclosporine after PUVA therapy has a higher incidence of squamous cell skin cancer. The risks are greatest with long-term and previous use of PUVA, methotrexate, or other immunosuppressants.)
To reduce complications of cyclosporine, the dosage is decreased after improvement occurs. Maintenance therapy is usually limited to a year, although some experts believe that a microemulsion form may be safe to use for up to 2 years. People should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.
People Who Should not Use Cyclosporine
Because the drug suppresses the immune system, people with active infections or cancer should avoid it. People with uncontrolled high blood pressure and impaired kidney function should also not use this medication. Cyclosporine therapy for children with psoriasis has not been well studied.
Drug and Food Interactions
Cyclosporine interacts with numerous drugs, including prescriptions, over-the-counter preparations and grapefruit and grapefruit juice.
Newer forms of cyclosporine that have fewer side effects are being investigated.
Biological Response Modifiers
Biological response modifiers, sometimes called "biologics," belong to a newer class of drugs that are considered the most exciting development in psoriasis treatment. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not affect the entire immune system like general immunosuppressants. Biologic drugs tend to be more expensive.
Biologics are traditionally second- or third-line treatments, but are quickly becoming the standard of care as first line treatments for moderate to severe psoriasis. Although studies of these medications have primarily been done on people who are over 18 years old, several are approved for patients under the age of 18.
The biologics traditionally used to treat plaque psoriasis (described below) are now also considered in the treatment of pustular psoriasis. Many studies testing new biologics are underway.
There are different types of biologics used to treat psoriasis:
- Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.
- Interleukin blocking monoclonal antibodies injections for 12 weeks. They need blood tests every 2 weeks.
Types of TNF blockers:
- Etanercept was the first approved biologic for the treatment of moderate-to-severe plaque psoriasis, and for people with psoriatic arthritis. The drug is given either alone or in combination with methotrexate. People inject themselves under the skin once or twice a week for 12 weeks at a higher dose and then drop down to a lower weekly dose. The drug may be effective in people with psoriasis who have not responded to other biologic drugs or other therapies, and it is also effective in people who have not yet received biologic treatments. It has been shown to be safe and effective for treating children with rheumatoid arthritis and in 2016 got the FDA indication for pediatric psoriasis.
- Adalimumab has been approved for moderate-to-severe chronic plaque psoriasis. It is given by injection weekly at first, and then bi-weekly long term. It appears better tolerated than methotrexate. This drug is also approved for psoriatic arthritis.
- Infliximab is a TNF inhibitor given by IV infusion. It is often considered for, second- or third-line therapy for chronic plaque psoriasis.
- Certolizumab is a monoclonal antibody targeting TNF-alpha approved for moderate to severe plaque psoriasis and psoriatic arthritis. It is administered by injection every other week.
Side effects and risks of TNF blockers:
- All of the TNF inhibitors carry the potential for an increased risk for serious infections. Upper respiratory infections are the most common infections that occur.
- Uncommon infections caused by fungi and tuberculosis bacteria also occur in people using anti-TNF medications. People using anti-TNF medications who display symptoms of body-wide (systemic) illness should be tested. Because these infections are uncommon, previous delays in diagnosis have resulted in death in some people.
- People receiving these drugs are at risk of reactivating old tuberculosis (TB) infections. People are also at a higher risk of developing TB. The FDA recommends TB screening with a purified protein derivation (PPD) skin test or a blood test called quantiferon gold.
- Whether TNF inhibitors increase the risk for lymphoma and skin cancers is a debated issue.
A number of other side effects are also possible.
Anti-interleukin monoclonal antibodies bind to proteins or cells and stimulate the immune system to destroy those cells. New monoclonal antibodies targeting various interleukins are continuously being developed. Currently FDA-approved anti-interleukin antibodies for psoriasis include:
- Ustekinumab is an anti-interleukin antibody approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. It is given by injection about every 3 months and may be used as first-line treatment with approval down to the age of 12.
- Secukinumab, ixekizumab, brodalumab, tildrakizumab, risankizumab, and guselkumab are other anti-interleukin antibody drugs approved for the treatment of moderate-to-severe plaque psoriasis. These medicines are very effective in achieving clearance of most of a person's psoriatic lesions.
Apremilast a PDE4 inhibitor, is an oral anti-inflammatory. It was approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. People may see an improvement in about 4 months when taken twice daily. Side effects may include:
- Upper respiratory tract infection
It has not yet been studied for safety in pregnant women. Unlike biologics, it is not associated with the reactivation of TB.
Other Second- and Third-Line Treatments
Some oral immunosuppressants being studied for psoriasis include tacrolimus, pimecrolimus, and sirolimus. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and have fewer side effects. (Some immunosuppressants are also being studied as topical treatments.)