Methotrexate and cyclosporine are proven effective treatments for psoriasis, but each presents unique clinical challenges, according to Dr. Bruce Strober.
"Both drugs are effective and safe if used correctly," said Dr. Strober of the New York University. Despite being relatively "old" medications, they remain important tools for the dermatologist, because not every patient is a good candidate for the newer biologics. Additionally, Dr. Strober noted at the seminar sponsored by Skin Disease Education Foundation (SDEF), "Biologics may fail as monotherapy, but succeed in combination with these traditional systemic medications." They can also be useful rescue therapies in tough clinical scenarios.
Dr. Bruce Strober
Methotrexate is especially attractive because of its moderate efficacy, simplicity of dosing, and low cost. Dr. Strober maintained that methotrexate should be considered as a first-line agent for many patients, whether they have Medicare, private insurance, or no insurance.
The downside of methotrexate can be its GI side effects; it also can exert some stress on the liver. Folic acid can help with both of those problems. "Folate supplementation reduces the incidence of hepatotoxicity and gastrointestinal intolerance without impairing the efficacy of methotrexate," Dr. Strober said. Folic acid and folinic acid are both equally effective, although folic acid is less expensive, and folinic acid must be dosed more than 6 hours from the dose of methotrexate
Methotrexate must never be administered to women who are trying to conceive, are pregnant or breastfeeding, he added. There are also some relative contraindications, including high alcohol intake; renal or liver disease, including fatty liver; hematologic abnormalities; active infectious disease; and latent infections with hepatitis B and C.
Although the risk of liver damage is low for cumulative doses of less than 3 g of methotrexate, higher doses and long-term therapy can raise the chance of hepatotoxicity as much as 25%. A liver biopsy should be considered in patients who surpass this cumulative level. But the liver biopsy should be viewed as an imperfect test with poor sensitivity, specificity, and procedural risks, he said.
Patients taking methotrexate should always undergo a complete blood count, liver function tests, a blood urea nitrogen and creatinine level check, and hepatitis serologies at baseline; blood counts and liver function tests should be monitored periodically throughout the treatment period.
Although rare, patients may experience idiopathic pulmonary disease due to methotrexate; therefore, unexplained cough and shortness of breath should be evaluated immediately.
Cyclosporine is more suited for patients with severe disease that requires rapid clearing. Also, cyclosporine is safe for pregnant patients and can be used for those who fail other treatments. At lower doses, it can be combined with biologics, noted Dr. Strober.
It is associated with more potential adverse effects than is methotrexate, however. Nephrotoxicity, hypertension, and an increased risk of some cancers are the primary risks, he reported. The drug can also cause electrolyte imbalances (including hypomagnesemia), increase lipid levels, and can cause headache or nausea, hypertrichosis, gingival hyperplasia, and paresthesias. "Cyclosporine has predictable toxicities, and, therefore, its use needs to be short in duration," said Dr. Strober.
Cyclosporine is relatively contraindicated in hypertensive patients, those with a history of nonmelanoma skin cancer, and patients with kidney problems, significant cardiovascular disease, or infections.
Baseline monitoring should include a complete blood count, a metabolic profile, serum magnesium, tuberculosis skin testing, and blood pressure. "Stress the risk of drug interactions to the patient, because cyclosporine is associated with many."
Dr. Strober is a consultant and on the advisory boards of Abbott, Amgen, Centocor Ortho Biotech, Pfizer, and Celgene. He has received honoraria from Abbott, Amgen, Centocor, and Pfizer. SDEF and this news organization are owned by Elsevier.