Think Efficacy and Toxicity in Selecting Psoriasis Medications

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.

PARIS — Nonbiologic systemic drugs can be effective choices for the treatment of psoriasis if they are chosen properly, according to Dr. Jonathan Barker.

“The important message is that standard, traditional systemic drugs work,” said Dr. Barker at the annual congress of the European Academy of Dermatology and Venereology. However, these drugs are not always effective and are often associated with considerable toxicity.

“To optimize systemic therapy, we're talking about maximizing efficacy and minimizing toxicity,” said Dr. Barker, head of the skin inflammation unit at St. John's Institute of Dermatology, King's College, London, who gave an overview of several standard systemic drugs.

▸ Methotrexate. The preferred drug for unrelenting disease that is likely to require long-term therapy, it is also effective for treating psoriatic arthritis said Dr. Barker. The key to avoiding adverse events with the drug is to start with a low dose and increase it slowly.

Dr. Barker said he and his colleagues begin psoriasis patients on 5 mg/week and increase the dose by 5 mg/week up to 15 mg for the first 3 months. The maximum dose they use for psoriasis patients is 25 mg.

It's not commonly recognized that most causes of death that are associated with methotrexate are attributable to bone marrow suppression, not hepatotoxicity. These deaths are usually a result of some confusion over the dosing regimen or folic acid deficiency, he said. Bone marrow suppression is rare when patients are on folic acid supplementation.

Dr. Barker noted that it is possible to monitor liver function without routine liver biopsy by monitoring serum procollagen III aminopeptide (Br. J. Dermatol. 2005;152:444–50). For his psoriasis patients on long-term methotrexate, he checks serum procollagen III aminopeptide every 3 months.

“If this practice were to be widely adopted, then methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy,” he said.

▸ Cyclosporine. It is a fast-acting drug that “presents a different set of problems with respect to usage,” Dr. Barker noted. “It's a very good drug for patients with intermittent disease, where they need a quick fix but you're hoping that the duration of therapy will be very short.”

Glomerular sclerosis is extremely unlikely to occur in patients who are treated with cyclosporine for less than 12 months and in whom there is an insignificant rise in creatinine levels. Glomerular sclerosis is much more likely to occur when cyclosporine is used for more than a year.

In addition, long-term cyclosporine A—the main form of this drug—is associated with an increased risk of nonmelanoma skin cancer. However, this risk can be minimized by limiting both dosage and duration of use (no longer than 1–2 years), said Dr. Barker. Cyclosporine use should be minimized in patients who have had significant phototherapy.

▸ Acitretin. It can be used “occasionally in moderate chronic plaque psoriasis, more so in palmo-plantar pustulosis,” said Dr. Barker, who added that he starts with the lowest dosage (25 mg/day) and uses it with narrow-band UVB phototherapy.

However, one should use extreme caution when treating women of child-bearing age with acitretin because it can cause major fetal abnormalities, he cautioned.

In addition, it is very helpful as an adjunctive treatment for patients with severe disease and multiple squamoproliferative lesions who have been on phototherapy in the past.

“This is not an immunosuppressive drug and there is some evidence that it has chemoprotective activity for malignancy,” he said.

Dr. Barker has consulted for several pharmaceutical companies making biologics but noted that none was relevant to his presentation.