Pegloticase Safe as Induction Therapy in Tophaceous Gout

SNOWMASS, COLO. – Many rheumatologists may have been scared off from using pegloticase in chronic refractory gout because of the much-publicized risk of infusion reactions – needlessly so, according to Dr. Robert L. Wortmann.

That safety concern has been resolved. Patients on pegloticase who are headed for an infusion reaction can now reliably be identified in advance so that the drug gets stopped before this complication ever occurs, Dr. Wortmann said at the symposium.

Pegloticase (Krystexxa) is a porcinelike pegylated uricase. A uric acid–lowering drug of unprecedented effectiveness, pegloticase converts urate to allantoin. Given intravenously at a dosage of 8 mg every 2 weeks, it quickly drives serum urate to close to 0 and keeps it there.

"Tophi will melt away before your eyes within about 12 weeks," said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Hanover, N.H.

In the major clinical trials, 25%-42% of treated patients had infusion reactions of varied severity. Those statistics have understandably put off a lot of rheumatologists. However, patients experience infusion reactions only when they develop blocking antibodies against the uricase. So as long as the most recent dose they received was effective, they will not have an infusion reaction to the next one.

"When using this agent, get a urate level in the morning, before the patient gets the infusion. If it’s less than 1 mg/dL, it’s okay to proceed," the rheumatologist said.

On the other hand, if the urate level is above about 4 mg/dL, the drug is no longer working. Blocking antibodies have formed, and the patient is at risk for an infusion reaction. It’s time to stop pegloticase for good and move on to other therapy, he continued.

"Pegloticase, to me, is an induction drug. If you’ve got a person who comes in with tophi all over the place, and they’re having a lot of acute gout attacks – maybe six or more per year – this is a great drug to try to get the total body urate pool decreased rapidly," Dr. Wortmann explained. "Once the tophi are gone, I think you can switch the patient to an oral agent. That’s how I use it. There have been people who’ve taken pegloticase for 2 years and continued to tolerate it, but if the tophi are gone, to me it’s time to move on to one of the other drugs."

Before utilizing pegloticase, it’s important to ensure that a patient doesn’t have hereditary glucose-6-phosphate dehydrogenase deficiency. Pretreatment with an antihistamine and a corticosteroid is recommended to help guard against infusion reactions.

Gout flares occur in close to three-quarters of pegloticase-treated patients in the first few months, so prophylaxis with colchicine and/or NSAIDs is a must, he said.

"Anything that lowers serum urate can trigger an attack, and the faster and further urate goes down, the more likely are flares. So these people need to have a lot of prophylaxis initially. Over time the flare rate goes down," Dr. Wortmann said.

He reported that he serves as a consultant to Savient, which markets pegloticase, as well as to Ardea Biosciences, Novartis, Takeda, and URL Pharmaceuticals.

SNOWMASS, COLO. – Many rheumatologists may have been scared off from using pegloticase in chronic refractory gout because of the much-publicized risk of infusion reactions – needlessly so, according to Dr. Robert L. Wortmann.

That safety concern has been resolved. Patients on pegloticase who are headed for an infusion reaction can now reliably be identified in advance so that the drug gets stopped before this complication ever occurs, Dr. Wortmann said at the symposium.

Pegloticase (Krystexxa) is a porcinelike pegylated uricase. A uric acid–lowering drug of unprecedented effectiveness, pegloticase converts urate to allantoin. Given intravenously at a dosage of 8 mg every 2 weeks, it quickly drives serum urate to close to 0 and keeps it there.

"Tophi will melt away before your eyes within about 12 weeks," said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Hanover, N.H.

In the major clinical trials, 25%-42% of treated patients had infusion reactions of varied severity. Those statistics have understandably put off a lot of rheumatologists. However, patients experience infusion reactions only when they develop blocking antibodies against the uricase. So as long as the most recent dose they received was effective, they will not have an infusion reaction to the next one.

"When using this agent, get a urate level in the morning, before the patient gets the infusion. If it’s less than 1 mg/dL, it’s okay to proceed," the rheumatologist said.

On the other hand, if the urate level is above about 4 mg/dL, the drug is no longer working. Blocking antibodies have formed, and the patient is at risk for an infusion reaction. It’s time to stop pegloticase for good and move on to other therapy, he continued.

"Pegloticase, to me, is an induction drug. If you’ve got a person who comes in with tophi all over the place, and they’re having a lot of acute gout attacks – maybe six or more per year – this is a great drug to try to get the total body urate pool decreased rapidly," Dr. Wortmann explained. "Once the tophi are gone, I think you can switch the patient to an oral agent. That’s how I use it. There have been people who’ve taken pegloticase for 2 years and continued to tolerate it, but if the tophi are gone, to me it’s time to move on to one of the other drugs."

Before utilizing pegloticase, it’s important to ensure that a patient doesn’t have hereditary glucose-6-phosphate dehydrogenase deficiency. Pretreatment with an antihistamine and a corticosteroid is recommended to help guard against infusion reactions.

Gout flares occur in close to three-quarters of pegloticase-treated patients in the first few months, so prophylaxis with colchicine and/or NSAIDs is a must, he said.

"Anything that lowers serum urate can trigger an attack, and the faster and further urate goes down, the more likely are flares. So these people need to have a lot of prophylaxis initially. Over time the flare rate goes down," Dr. Wortmann said.

He reported that he serves as a consultant to Savient, which markets pegloticase, as well as to Ardea Biosciences, Novartis, Takeda, and URL Pharmaceuticals.

SNOWMASS, COLO. – Many rheumatologists may have been scared off from using pegloticase in chronic refractory gout because of the much-publicized risk of infusion reactions – needlessly so, according to Dr. Robert L. Wortmann.

That safety concern has been resolved. Patients on pegloticase who are headed for an infusion reaction can now reliably be identified in advance so that the drug gets stopped before this complication ever occurs, Dr. Wortmann said at the symposium.

Pegloticase (Krystexxa) is a porcinelike pegylated uricase. A uric acid–lowering drug of unprecedented effectiveness, pegloticase converts urate to allantoin. Given intravenously at a dosage of 8 mg every 2 weeks, it quickly drives serum urate to close to 0 and keeps it there.

"Tophi will melt away before your eyes within about 12 weeks," said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Hanover, N.H.

In the major clinical trials, 25%-42% of treated patients had infusion reactions of varied severity. Those statistics have understandably put off a lot of rheumatologists. However, patients experience infusion reactions only when they develop blocking antibodies against the uricase. So as long as the most recent dose they received was effective, they will not have an infusion reaction to the next one.

"When using this agent, get a urate level in the morning, before the patient gets the infusion. If it’s less than 1 mg/dL, it’s okay to proceed," the rheumatologist said.

On the other hand, if the urate level is above about 4 mg/dL, the drug is no longer working. Blocking antibodies have formed, and the patient is at risk for an infusion reaction. It’s time to stop pegloticase for good and move on to other therapy, he continued.

"Pegloticase, to me, is an induction drug. If you’ve got a person who comes in with tophi all over the place, and they’re having a lot of acute gout attacks – maybe six or more per year – this is a great drug to try to get the total body urate pool decreased rapidly," Dr. Wortmann explained. "Once the tophi are gone, I think you can switch the patient to an oral agent. That’s how I use it. There have been people who’ve taken pegloticase for 2 years and continued to tolerate it, but if the tophi are gone, to me it’s time to move on to one of the other drugs."

Before utilizing pegloticase, it’s important to ensure that a patient doesn’t have hereditary glucose-6-phosphate dehydrogenase deficiency. Pretreatment with an antihistamine and a corticosteroid is recommended to help guard against infusion reactions.

Gout flares occur in close to three-quarters of pegloticase-treated patients in the first few months, so prophylaxis with colchicine and/or NSAIDs is a must, he said.

"Anything that lowers serum urate can trigger an attack, and the faster and further urate goes down, the more likely are flares. So these people need to have a lot of prophylaxis initially. Over time the flare rate goes down," Dr. Wortmann said.

He reported that he serves as a consultant to Savient, which markets pegloticase, as well as to Ardea Biosciences, Novartis, Takeda, and URL Pharmaceuticals.