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C1 esterase inhibitor concentrates and attenuated androgens

2018; Elsevier BV; Volume: 391; Issue: 10128 Linguagem: Inglês

10.1016/s0140-6736(18)30583-x

1474-547X

Yannick D. Müller, Thomas Harr, Eric Dayer, Jörg D. Seebach,

Peptidase Inhibition and Analysis

Marc A Riedl and colleagues (July 25, 2017, p 1595)1Riedl MA Grivcheva-Panovska V Moldovan D et al.Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial.Lancet. 2017; 390: 1595-1602Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar conducted a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial in 32 patients to test the prophylactic efficacy of recombinant human C1 esterase inhibitor for hereditary angio-oedema. Once or twice weekly administration of recombinant human C1 esterase inhibitor (50 IU/kg) reached the primary endpoint (reduced number of attacks) in an intention-to-treat analysis. Notably, most of the study population had never received prophylactic treatment before study enrolment, although attenuated androgens or tranexamic acid were permitted per protocol. This situation suggests that patients under conventional prophylaxis did not meet the inclusion criteria of frequent attacks (ie, four or more per month for at least 3 consecutive months before study initiation). Furthermore, we would like to emphasise the potential synergistic effect of recombinant human C1 esterase inhibitor and attenuated androgens for prophylaxis of hereditary angio-oedema as shown by the following case.2Muller YD Oppliger R Breguet R et al.Hereditary haemorrhagic telangiectasia: to transplant or not to transplant—is there a right time for liver transplantation.Liver Int. 2016; 36: 1735-1740Crossref PubMed Scopus (9) Google Scholar The patient was successfully treated for 26 years with attenuated androgens (danazol) until the age of 55 years when she developed new recurrent attacks. Danazol was switched to regular plasma-derived C1 esterase inhibitor (berinert) administered every 14 days, which was insufficient to prevent attacks—as shown by serial measurements of antigenic C1 esterase inhibitor levels. Clinical remission was achieved when danazol was reintroduced (figure). Hereditary angio-oedema can be controlled by adequate substitution with C1 esterase inhibitor concentrates, as demonstrated by an inverse relationship between the relative risk of attack and functional C1 esterase inhibitor activity.3Longhurst H Cicardi M Craig T et al.Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor.N Engl J Med. 2017; 376: 1131-1140Crossref PubMed Scopus (142) Google Scholar However, plasma-derived and recombinant C1 esterase inhibitors are very expensive, whereas attenuated androgens are affordable and efficient for prophylaxis of hereditary angio-oedema. Further studies should definitively analyse the potential synergistic effect between C1 esterase inhibitor concentrates and attenuated androgens. Cost-effectiveness of long-term prophylaxis of hereditary angio-oedema might be substantially improved as a result. We declare no competing interests. YDM was supported by the Swiss National Research Fund (grant no. P300PB_174500). Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trialProphylaxis with recombinant human C1 esterase inhibitor provided clinically relevant reductions in frequency of hereditary angio-oedema attacks and was well tolerated. In view of the pharmacokinetic profile of recombinant human C1 esterase inhibitor, our results suggest that efficacy of C1-inhibitor replacement therapy might not be a direct function of plasma trough concentrations of C1 inhibitor. Full-Text PDF C1 esterase inhibitor concentrates and attenuated androgens – Authors' replyWe thank Yannick D Muller and colleagues for their interest in our Article1 describing results from a randomised, double-blind, placebo-controlled study with the use of recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema. Full-Text PDF