Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Developing a framework for assessing respiratory sensitization: A workshop report

Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, –omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment

Impact of a Cleaners’ Strike on Compensation Claims for Asthma among Teachers in Ontario

BACKGROUND: A review of Workplace Safety and Insurance Board (WSIB) claims in Ontario from 1998 to 2002 showed an unusual spike in the number of claims accepted for work-exacerbated asthma (WEA) in April 2001

Impact of a Cleaners’ Strike on Compensation Claims for Asthma among Teachers in Ontario

BACKGROUND: A review of Workplace Safety and Insurance Board (WSIB) claims in Ontario from 1998 to 2002 showed an unusual spike in the number of claims accepted for work-exacerbated asthma (WEA) in April 2001.OBJECTIVE: To identify the cause for the spike in the number of WSIB claims for WEA in April 2001.METHODS: File reviews were performed to identify the occupations of workers with claims accepted for WEA in April 2001 compared with claims during March and May 2001, and during the same months in 2000 and 2002.RESULTS: In April 2001, there were 61 accepted WEA claims; the most common occupation was ‘teacher’. In contrast, among educational workers, there was only one WEA claim in the previous month and one in the following month. From March to May in the preceding and following years, there were only four and two claims, respectively. The most frequently implicated causative agents were dust and dirt exposure, which were responsible for 98% of claims; the mean (± SD) number of lost workdays was 6.5±10. The only identified environmental change associated with this spike was a cleaners’ strike at all elementary and high schools in the Toronto District School Board in Ontario, which started on March 31, 2001 and ended on May 1, 2001.CONCLUSION: The spike in accepted WEA claims in Ontario in April 2001 was temporally associated with a strike by Toronto District School Board cleaners, suggesting acute symptomatic effects of poor workplace (school) maintenance on asthmatic employees. The WSIB database was sufficiently sensitive to capture this phenomenon.Peer Reviewe