Jan Chlumsky

Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE).

BACKGROUND Purified α1 proteinase inhibitor (A1PI) slowed emphysema progression in patients with severe α1 antitrypsin deficiency in a randomised controlled trial (RAPID-RCT), which was followed by an open-label extension trial (RAPID-OLE). The aim was to investigate the prolonged treatment effect of A1PI on the progression of emphysema as assessed by the loss of lung density in relation to RAPID-RCT. METHODS Patients who had received either A1PI treatment (Zemaira or Respreeza; early-start group) or placebo (delayed-start group) in the RAPID-RCT trial were included in this 2-year open-label extension trial (RAPID-OLE). Patients from 22 hospitals in 11 countries outside of the USA received 60 mg/kg per week A1PI. The primary endpoint was annual rate of adjusted 15th percentile lung density loss measured using CT in the intention-to-treat population with a mixed-effects regression model. This trial is registered with ClinicalTrials.gov, number NCT00670007. FINDINGS Between March 1, 2006, and Oct 13, 2010, 140 patients from RAPID-RCT entered RAPID-OLE: 76 from the early-start group and 64 from the delayed-start group. Between day 1 and month 24 (RAPID-RCT), the rate of lung density loss in RAPID-OLE patients was lower in the early-start group (-1·51 g/L per year [SE 0·25] at total lung capacity [TLC]; -1·55 g/L per year [0·24] at TLC plus functional residual capacity [FRC]; and -1·60 g/L per year [0·26] at FRC) than in the delayed-start group (-2·26 g/L per year [0·27] at TLC; -2·16 g/L per year [0·26] at TLC plus FRC, and -2·05 g/L per year [0·28] at FRC). Between months 24 and 48, the rate of lung density loss was reduced in delayed-start patients (from -2·26 g/L per year to -1·26 g/L per year), but no significant difference was seen in the rate in early-start patients during this time period (-1·51 g/L per year to -1·63 g/L per year), thus in early-start patients the efficacy was sustained to month 48. INTERPRETATION RAPID-OLE supports the continued efficacy of A1PI in slowing disease progression during 4 years of treatment. Lost lung density was never recovered, highlighting the importance of early intervention with A1PI treatment. FUNDING CSL Behring.

Reduction in oral corticosteroid use in patients with severe allergic (IgE-mediated) asthma receiving omalizumab in a real-world setting

Background Patients with severe allergic asthma (SAA) are often inadequately controlled despite available treatments including high-dose inhaled corticosteroids and longacting b2-agonists. Use of oral corticosteroids (OCS) in SAA patients may not achieve full asthma control, and leads to significant long-term side effects. Omalizumab is a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody approved in the European Union as an add-on therapy for patients with SAA. In clinical studies, omalizumab has been shown to reduce OCS use. Here we report the effect of omalizumab treatment on OCS maintenance use for up to 24 months in patients with SAA in the real-world eXpeRience registry.

Safety of biweekly alpha1 antitrypsin treatment in the RAPID program

α1-antitrypsin (α1-AT) deficiency is a hereditary disorder characterised by an abnormally low concentration of functional α1-AT in blood and tissues [1]. The primary role of α1-AT is to protect elastin-containing tissues, most notably the lung, against the destructive activity of proteolytic enzymes [2]. Patients with severe α1-AT deficiency present with serum α1-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]. Administration of 120 mg·kg−1 α1-antitrypsin on a biweekly basis was safe and well tolerated http://ow.ly/CVbz30lUBum