Weekly AATD Infusions: Peak-to-Trough Levels in Practice

"Weekly AATD Infusions: Peak-to-Trough Levels in Practice" looks at how the pharmacokinetics of weekly dosing play out in real patients.

Dr. Haumschild describes the pharmacokinetic profile of weekly plasma-derived therapy, with a peak shortly after infusion and a trough before the next dose. He asks Dr. Goldklang about the clinical consequences of those troughs and how peak-to-trough dynamics affect her view of adequacy.

Dr. Goldklang agrees that a truly physiologic regimen would require dosing daily or every other day, which is not feasible. The community settled on weekly infusions. Levels are well above normal for the first two days, and the goal is to remain above 11 micromolar on the lowest day. She reminds the panel that patients have exacerbations, during which neutrophils consume alpha-1 antitrypsin. Her center teaches patients that hospitalization for an exacerbation is a time to receive augmentation, sometimes with an infusion a day or two early.

She also weighs practical realities. For a patient traveling to Florida, she may double the dose every other week. For a patient four hours from the nearest infusion center, weekly infusion may be unrealistic. Most of her colleagues give 60 mg/kg weekly nearly every week of the year. She would rather see a patient on 120 mg every other week than on nothing, accepting some time below 11 micromolar.

Asked when she measures troughs, Dr. Goldklang says she does not. If she did, she would draw it on the day of infusion. No payer has required trough levels. Some payers have asked her to prove that levels remain low during therapy or to show efficacy through improved PFTs, and she responds that those requests are unreasonable. She does not want patients preoccupied with their troughs.

Dr. Sandhaus adds that his group discourages level testing on therapy, because it leads clinicians to chase their tails and raise doses while troughs remain similar.

In "AATD Augmentation Adherence, Infusion Burden, and Plasma Supply," the panel will look at Dr. Sandhaus's data on how many patients actually start and stay on weekly infusions, and at the vulnerabilities of a plasma-based supply.