The medical journal The Lancet Respiratory Medicine on Thursday, Dec. 1, published findings of the RAPID Open Label Extension study of augmentation therapy for patients with emphysema and Alpha-1 Antitrypsin Deficiency.
N. Gerard McElvaney, MD, lead author
The original RAPID trial, sponsored by CSL Behring, randomly assigned 180 Alphas with emphysema to receive either augmentation therapy or a placebo for two years. RAPID results showed that Alphas who received augmentation therapy had less lung destruction than those on placebo.
In the extension trial, lasting another two years, all subjects received augmentation therapy. The extension trial was offered to all who participated in the original two-year RAPID trial and lived in countries where augmentation therapy was unavailable - 11 countries in all.
"The extension trial is quite remarkable," commented Robert Sandhaus, MD, PhD, who was an investigator in the original RAPID trial but not involved in the extension trial.
"The extension trial showed that Alphas who received augmentation therapy in the original two years of the RAPID trial continued to show less lung destruction for a full four years while receiving augmentation, and in fact the rate of destruction continued to decline," Sandhaus said. "But the extension trial also showed that no matter when augmentation is started, it will slow lung destruction."
Sandhaus, who is clinical director of the Alpha-1 Foundation and medical director of AlphaNet, said the final message is clear: "The earlier augmentation therapy is begun, the more lung tissue will be saved."
The extension study consisted of two groups:
Any RAPID study participant who was randomized to receive augmentation therapy for the first two years, wound up receiving a total of four years of augmentation therapy. Any RAPID participant who had been in the placebo group received augmentation therapy only during the two years of the extension study. All participants received CT scans at intervals throughout the RAPID trial and the extension study in order to assess loss of lung tissue over time.
The "Early-Start" group received Alpha-1 augmentation therapy (Zemaira) during both trials, providing up to four years of continuous treatment, while the "Delayed-Start" group received a placebo during the first two years and then switched to Zemaira in the extension trial, providing up to two years of active treatment.
Both groups had a similar rate of lung function decline in the last two years when everyone received augmentation therapy. But the "Early-Start" group maintained its advantage, experiencing a lower overall rate of lung density decline. During the extension trial, the "Delayed-Start" group failed to catch-up to their "Early-Start" counterparts.
"RAPID is a landmark study on the disease-modifying effect of A1-PI therapy on the progression of emphysema in patients with severe AATD," said Professor N. Gerard McElvaney, Head of the Department of Medicine Respiratory Research Division, at Beaumont Hospital, Dublin, Royal College of Surgeons in Ireland (RCSI) and lead author of the article.
"With the publication of the RAPID extension study, we have found that the late introduction of A1-PI therapy is still beneficial – but the lung structure lost by the late introduction is never recovered. RAPID's message is to intervene. The RAPID extension message is to intervene early," said Kenneth Chapman, MD, director of the Asthma & Airway Centre at the University Health Network in Toronto, Canada.
The full CSL press release
Summary of The Lancet Respiratory Medicine article