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 or injection. The medicines can have significant side effects and are generally reserved for severe psoriasis.
Systemic medications approved for treating psoriasis include:
- Biologic Response Modifiers
Off-label Systemics. 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, patients 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 new agents to treat psoriasis are under study, including oral medications and monoclonal antibodies. The following agents show promising results for plaque psoriasis but none have yet been approved for use:
- Apremilast (oral anti-inflammatory)
- IxekizumabI (anti-interleukin-17 monoclonal antibody)
- Brodalumab (anti-interleukin-17-monoclonal antibody)
- Certolizumabpegol, or CZP (antitumor necrosis factor [TNF] agent)
Methotrexate (Rheumatrex) 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.
The drug is taken weekly, not daily.
Side Effects. Many patients 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. Patients should ask their doctor if they should take folic acid supplements (generally recommended at 1 mg daily).
More serious, but relatively uncommon side effects include:
- Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. Patients 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 patients with existing liver problems. Regular monitoring for liver toxicity includes blood tests and sometimes liver biopsies. Patients 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 patients with generalized erythrodermic and pustular psoriasis.
Methotrexate appears to be effective in children, but more safety research is needed.
Drug Interactions. 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. Patients 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 (Soriatane) and isotretinoin (Accutane).
Acitretin 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 PUVA phototherapy it can markedly improve the response, even in patients with these forms of psoriasis.
Accutane, more commonly used to treat acne, 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.
Combination therapy. 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.
Side Effects. 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. Patients experiencing these symptoms should call a doctor immediately and stop taking the drug.
Oral retinoids should not be taken during pregnancy.
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 ensures that no woman starts retinoid therapy while pregnant or trying to get pregnant.
Cyclosporine (Neoral, Sandimmune, SangCya) 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. Neoral is the preparation used most often for psoriasis, and it clears psoriasis in many patients within 8 - 12 weeks.
Side Effects. Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for patients who do not respond to phototherapy or less potent systemic medications (for example, 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 (Patients who take cyclosporine after PUVA therapy have 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 of Neoral (Neoral-Neo) may be safe to use for up to 2 years. Patients should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.
Patients Who Should not Use Cyclosporine. Because the drug suppresses the immune system, people with active infections or cancer should avoid it. Patients 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 -- both prescription and over-the-counter preparations -- as well as 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 new 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 damage the entire immune system like general immunosuppressants. Biologic drugs are expensive.
Biologics are traditionally second- or third-line treatments, and may be used alone or in combination with first-line systemic drugs. Depending on the severity of psoriasis, some of these drugs may be used earlier in the course of treatment. Studies of these medications have primarily been done on patients who are over 18 years old.
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:
- T-cell blockers block immune cells linked to inflammation.
- Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.
Types of T-cell blockers:
- Alefacept (Amevive). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. It is very effective for psoriasis of the scalp. However, it doesn't work for all patients. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. They need blood tests every 2 weeks to make sure T cell levels do not drop too low. Side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infections and cancer.
Types of TNF blockers:
- Etanercept (Enbrel) is approved 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. Side effects include infections and lymphoma. Patients inject themselves under the skin once or twice a week for 12 weeks. Continuing etanercept after 12 weeks may lower the severity of disease without increasing infections or side effects. The drug may be effective in psoriasis patients who have not responded to other biologic drugs or other therapies, and it is also effective in patients who have not yet received biologic treatments. Although etanercept has not been studied in children who have psoriasis, it has been shown to be safe and effective for treating children with rheumatoid arthritis.
- Adalimumab (Humira) has been approved for moderate-to-severe chronic plaque psoriasis. It is given by injection weekly at first, and then bi-weekly. It appears better tolerated than methotrexate. This drug is also approved for psoriatic arthritis.
- Infliximab (Remicade) is a TNF inhibitor given by injection. It is often considered for,second- or third-line therapy for chronic plaque psoriasis.
- Golimumab (Simponi) is approved for the treatment of active psoriatic arthritis. It is patient-administered by injection and taken once per month. It is sometimes combined with methotrexate. Side effects include increased risk of infection, cancers and lymphoma, cardiac conditions, liver or nervous system disorders.
Side effects and risks of TNF blockers:
- All of the TNF inhibitors carry the potential for an increased risk of serious infections. Upper respiratory infections are the most common infections that occur.
- Uncommon infections caused by fungi and tuberculosis bacteria also boccur in people using anti-TNF medications. In 2009, the FDA issued a warning to healthcare professionals, stressing the need to test for these infections in people using anti-TNF medications who display symptoms of body-wide (systemic) illness. Because these infections are uncommon, previous delays in diagnosis have resulted in death in some patients.
- Patients receiving these drugs are at risk of reactivating old tuberculosis (TB) infections. Patients are also at higher risk for developing TB. The FDA recommends TB screening with a purified protein derivation (PPD) skin test.
- Whether TNF inhibitors increase the risk for lymphoma and skin cancers is a debated issue.
A number of other side effects are also possible.
Human monoclonal antibodies bind to proteins or cells and stimulate the immune system to destroy those cells.
- Ustekinumab (Stelera) was approved by the FDA in 2009 for the treatment of moderate to severe plaque psoriasis. It is given by injection about every 3 months and may be used as first-line treatment. Patients should discontinue use prior to any elective surgery, or after 4 months of treatment without adequate response. In 2013, it was FDA approved to treat psoriatic arthritis.
Other Second- and Third-Line Treatments
Immunosuppressants. Some oral immunosuppressants being studied for psoriasis include tacrolimus (Prograf), pimecrolium, 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.)