Psoriasis response at 2 months guides methotrexate decision

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.

LAS VEGAS – If psoriasis patients don’t improve after 2 months of methotrexate therapy, the drug’s probably not going to work, according to Dr. Bruce Strober, of the University of Connecticut in Farmington.

But "don’t give up" if there’s even a slight improvement at that point. Up to 45% of patients achieve psoriasis area and severity index (PASI) scores of 75 on methotrexate, but "you really have to allow the drug 24 weeks to see that. If you see any hint of efficacy, keep going," he said at the SDEF Las Vegas Dermatology Seminar.

Dr. Strober shared insights about using methotrexate culled from more than a decade of experience. He starts most patients on 15 mg/week, but smaller people at perhaps 10-12.5 mg. He’ll dose down the elderly, as well, if he suspects renal insufficiency.

"I give it all in one dose, except if it’s at 17.5 mg or more per week, then I will divide the dose, either half in the morning, half at night," or a few days apart. "I never do the q [every] 12 hours x 3-day dosing. It’s based on no science, and you don’t have to make your patient’s life so hard," he said.

Not infrequently, Dr. Strober has patients self-inject a subcutaneous formulation in lieu of oral therapy. "It likely has better bioavailability and efficacy, [and] studies suggest avoiding first pass metabolism" is safer for the liver. Liver toxicity will be a problem in up to a quarter of patients, with the obese perhaps facing a higher risk. As with CBC and renal function, monthly liver testing is a must with methotrexate, at least for the first year.

"I don’t do liver biopsies anymore. I think it’s an extremely poor test laden with sampling error, and it has its own risks," he said. Instead, "I use liver function tests pretty exclusively" to look for marked, persistent LFT [liver function test] elevations above baseline, even if patients stay in the normal range. "Not uncommonly, a patient’s LFT could be 15 over 16 AST [aspartate aminotransferase] over ALT [alanine aminotransferase], and then 3 months into methotrexate, 45 over 42. It might be in the normal range, but I think that should give you pause. You caused a threefold increase in the liver tests," he said.

"Liver-induced changes are reversible if you react early enough by reducing the dose or just stopping the drug," Dr. Strober said.

Folate supplementation helps to protect the liver and reduce GI side effects. Dr. Strober often adds folinic acid, three 5 mg-doses per week, if GI side effects persist with folic acid alone. It’s as effective as folic acid, but "folic acid is cheaper. That’s why I start with it," he said.

The risk of pancytopenia is increased with poor renal function or use of sulfonamide-based antibiotics. "Monitor the CBC closely in the first few visits. You need folinic acid for rescue if it becomes a problem," he said.

Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen. SDEF and this news organization are owned by Frontline Medical Communications.