Safety of biweekly α₁-antitrypsin treatment in the RAPID programme

Abstract

α 1 -antitrypsin (α 1 -AT) deficiency is a hereditary disorder characterised by an abnormally low concentration of functional α 1 -AT in blood and tissues [1]. The primary role of α 1 -AT is to protect elastin-containing tissues, most notably the lung, against the destructive activity of proteolytic enzymes [2]. Patients with severe α 1 -AT deficiency present with serum α 1 -AT concentrations <11 μM and are prone to destruction of the lung tissue, often developing respiratory symptoms and emphysema in the fourth or fifth decade of life [3, 4].

<p>New Patient-Centric Approaches to the Management of Alpha-1 Antitrypsin Deficiency</p>

“…In the RAPID clinical trial program, a subgroup of patients received bi-weekly infusions at the discretion of the treating physician to cover periods where they were unable to attend the clinic, eg, during vacations. 59 Overall, there were 933 biweekly infusions during the RAPID clinical trial program, and results showed similar rates, temporal distribution and severity of adverse events between weekly dosing with 60 mg/kg and bi-weekly dosing with 120 mg/kg AAT. 59 Therefore, given the favorable pharmacokinetic and safety profiles of bi-weekly dosing, and the willingness of AATD experts to utilize alternative dosing strategies, there is an increasingly strong rationale for the implementation of extended-interval dosing when required.…”

“…59 Overall, there were 933 biweekly infusions during the RAPID clinical trial program, and results showed similar rates, temporal distribution and severity of adverse events between weekly dosing with 60 mg/kg and bi-weekly dosing with 120 mg/kg AAT. 59 Therefore, given the favorable pharmacokinetic and safety profiles of bi-weekly dosing, and the willingness of AATD experts to utilize alternative dosing strategies, there is an increasingly strong rationale for the implementation of extended-interval dosing when required. However, the standard dose remains the preferred choice of treatment as there are no specific efficacy data related to the 120 mg/kg biweekly dose and no data on the impact of differing trough levels between weekly and bi-weekly dosing on the efficacy of treatment.…”

A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application

“…Double dosing was found to be effective at further reducing the level of serine proteases in both the airway and circulation, reducing elastin degradation, and diminishing airway inflammation when compared to standard dose therapy [ 168 , 169 ]. The RAPID Programme also demonstrated that biweekly dosing with 120 mg/kg of AAT is a safe, well tolerated and a convenient alternative to the dosing regimen currently recommended by the FDA [ 170 ]. The SPARTA trial is currently ongoing in a number of European countries to further explore the efficacy and safety of AAT in subjects with pulmonary emphysema due to AATD (NCT01983241).…”

Alpha 1 Antitrypsin Therapy in Patients with Alpha 1 Antitrypsin Deficiency: Perspectives from a Registry Study and Practical Considerations for Self-Administration During the COVID-19 Pandemic

“…Alternative dosing strategies such as bi-weekly infusion of AAT therapy have been trialed 10,72 and offer favorable pharmacokinetic and tolerability profiles. 10,73 Certainly, as future data concerning dose optimization and dosage interval become available, the possibility of implementing extended-interval dosages of AAT therapy may enhance the attractiveness of self-administration therapy in patients with AATD in the years to come.…”