- Email: [email protected]
Absence of Inhibitory Anti-C1 Esterase-Inhibitor Antibody Formation in Subjects Treated With C1 Esterase-Inhibitor Concentrate (Berinert®) for Successive Hereditary Angioedema Attacks
Abstracts AB221
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
830
Absence of Inhibitory Anti-C1 Esterase-Inhibitor Antibody Formation in Subjects Treated With C1 Esterase-Inhibitor Concentrate (BerinertÒ) for Successive Hereditary Angioedema Attacks D. S. Hurewitz1, J. A. Bernstein2, A. K. Bewtra3, U. Kalina4, T. Machnig4, T. J. Craig5; 1Allergy Clinic of Tulsa, Tulsa, OK, 2University of Cincinnati Medical Center and Bernstein Clinical Research Center, Cincinnati, OH, 3Creighton University School of Medicine, Omaha, NE, 4 CSL Behring, Marburg, GERMANY, 5Penn State University, Hershey, PA. RATIONALE: Limited data are available on the occurrence of autoantibodies to C1 esterase-inhibitor (C1-INH) in patients with hereditary angioedema (HAE) after treatment with C1-INH concentrate. In the I.M.P.A.C.T studies, we assessed the development of anti-C1-INH antibodies. METHODS: During treatment with C1-INH concentrate (BerinertÒ, CSL Behring, Marburg) for successive HAE attacks, anti-C1-INH antibodies were evaluated approximately every 3 months after a baseline assessment, using a direct binding enzyme-linked immunosorbent assay (screening assay, confirmatory assay for determination of isotypes, and anti-C1-INH antibody inhibition assay based on the VIII-Bethesda assay). RESULTS: No inhibitory anti-C1-INH antibodies were detected in the 57 subjects during a median study duration of 24 months. Nineteen subjects _1:50); 8 of these subjects _1 antibody-positive result (titer > (33%) had > already had antibody-positive results before enrollment. For 3 subjects with antibody-positive results, anti-C1-INH antibody tests returned to antibody-negative at later measurements, suggesting fluctuations in this variable. The majority of positive samples (63%) were confirmed by _1 antibody-positive result (n519) and isotyping. Between subjects with > subjects without antibodies (n538), there were no clinically relevant differences in the efficacy of C1-INH concentrate (medians of individual average values: 32 and 24 min for time to onset of symptom relief; 15.5 and 15.4 hours for time to complete resolution of HAE symptoms) or the proportion of subjects experiencing adverse events (47.4% and 42.1%). CONCLUSIONS: There is no indication for the development of inhibitory anti-C1-INH antibodies in subjects treated with C1-INH concentrate for HAE attacks, and the presence of non-inhibitory antibodies does not seem to be of clinical relevance.
complete resolution were considerably faster with 20 U/kg C1-INH vs. _6 hours, HRs for 20 U/ placebo (HRs: 3.36 and 4.30). When treated after > kg C1-INH vs. placebo were substantially reduced for time to onset of symptom relief and complete resolution (1.18 and 1.61). Linear regression also indicated longer times to complete resolution with later treatment. CONCLUSIONS: Early treatment of HAE attacks (<6 hours) with C1INH provides better treatment response than later treatment.
832
Management of paediatric patients with Hereditary Angioedema (HAE)- A retrospective evaluation of 120 patients from 91 families I. Martinez-Saguer, E. Aygoeren-Puersuen, E. Rusicke, T. Klingebiel, W. Kreuz; J.-W. Goethe University Hospital Frankfurt, Germany, Frankfurt, GERMANY. RATIONALE: Although the early manifestations of HAE occur during the initial 2 decades of life, there is limited published experience regarding management of paediatric patients with HAE. METHODS: In a retrospective chart review we evaluated our paediatric patient cohort of 120 patients from 91 families in respect to diagnosis, symptoms presentation and treatment response to human pasteurised C1INH concentrate (BerinertÒ). RESULTS: Our 120 paediatric HAE patients from 91 families at our Frankfurt-CCC have a median age of 10.94 years (range 0.6-17.7 years), female (n562) and male (n558). Observation period was 4.51 years (median, range 0.02-17.6 years). 75 of 120 patients received treatment at first clinical manifestation or for short-term prophylaxis. Nine patients experienced the first HAE attack during the first year of life. The most common localisation of oedema occurred at the extremities, GI tract, urogenital tract, and face. All HAE patients used body-weight adjusted dosing with 20U C1INH/kg BW. Most patients were treated on-demand _ 1 attack/ week individualised replacement (n5 114) and in patients with > therapy (IRT) (n56) was used. Home therapy was practised in 28 patients (24%). Overall, onset of relief was very fast, reliable and treatment was well tolerated. CONCLUSIONS: Early diagnosis is the cornerstone of successful management of HAE in paediatric patients. Body-weight adjusted human pasteurised C1INH concentrate is the first-line therapy for the symptomatic treatment of paediatric HAE patients.
Effect of Time to Treatment on Treatment Response With C1 Esterase-Inhibitor Concentrate (BerinertÒ) for Acute Hereditary Angioedema Attacks J. A. Bernstein1, D. S. Hurewitz2, A. K. Bewtra3, T. Machnig4, H. Keinecke5, T. J. Craig6; 1University of Cincinnati Medical Center and Bernstein Clinical Research Center, Cincinnati, OH, 2Allergy Clinic of Tulsa, Tulsa, OK, 3Creighton University School of Medicine, Omaha, NE, 4CSL Behring GmbH, Marburg, GERMANY, 5Accovion GmbH, Marburg, GERMANY, 6Penn State University, Hershey, PA. RATIONALE: Treatment with C1 esterase-inhibitor (C1-INH) concentrate (BerinertÒ, CSL Behring, Marburg) is well established for hereditary angioedema (HAE) attacks; treatment as early as possible is recommended. To investigate the relationship between time to treatment and treatment response, we conducted a post-hoc analysis of data from the I.M.P.A.C.T studies. _6 hours) METHODS: The relationship between time to treatment (<6 or > and efficacy (times to onset of symptom relief and complete resolution) was evaluated by Cox-regression for I.M.P.A.C.T.1, including hazard ratios (HRs; 10 or 20 U/kg C1-INH or placebo), and by linear regression for I.M.P.A.C.T.2 (20 U/kg C1-INH). HRs >1 indicate higher probabilities for faster relief or resolution with C1-INH vs. placebo. RESULTS: With 20 U/kg C1-INH in I.M.P.A.C.T.1 and I.M.P.A.C.T.2 (per-attack analysis), median times to onset of symptom relief were similar _6 hours (31 and 16 after treatment within 6 hours (30 and 25 min) and > min). Median times to complete resolution were shorter after treatment _6 hours (7.9 and 14.4 within 6 hours (2.8 and 12.6 hours) compared with > hours). After treatment within 6 hours, times to onset of symptom relief and
TUESDAY
831
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
830
Absence of Inhibitory Anti-C1 Esterase-Inhibitor Antibody Formation in Subjects Treated With C1 Esterase-Inhibitor Concentrate (BerinertÒ) for Successive Hereditary Angioedema Attacks D. S. Hurewitz1, J. A. Bernstein2, A. K. Bewtra3, U. Kalina4, T. Machnig4, T. J. Craig5; 1Allergy Clinic of Tulsa, Tulsa, OK, 2University of Cincinnati Medical Center and Bernstein Clinical Research Center, Cincinnati, OH, 3Creighton University School of Medicine, Omaha, NE, 4 CSL Behring, Marburg, GERMANY, 5Penn State University, Hershey, PA. RATIONALE: Limited data are available on the occurrence of autoantibodies to C1 esterase-inhibitor (C1-INH) in patients with hereditary angioedema (HAE) after treatment with C1-INH concentrate. In the I.M.P.A.C.T studies, we assessed the development of anti-C1-INH antibodies. METHODS: During treatment with C1-INH concentrate (BerinertÒ, CSL Behring, Marburg) for successive HAE attacks, anti-C1-INH antibodies were evaluated approximately every 3 months after a baseline assessment, using a direct binding enzyme-linked immunosorbent assay (screening assay, confirmatory assay for determination of isotypes, and anti-C1-INH antibody inhibition assay based on the VIII-Bethesda assay). RESULTS: No inhibitory anti-C1-INH antibodies were detected in the 57 subjects during a median study duration of 24 months. Nineteen subjects _1:50); 8 of these subjects _1 antibody-positive result (titer > (33%) had > already had antibody-positive results before enrollment. For 3 subjects with antibody-positive results, anti-C1-INH antibody tests returned to antibody-negative at later measurements, suggesting fluctuations in this variable. The majority of positive samples (63%) were confirmed by _1 antibody-positive result (n519) and isotyping. Between subjects with > subjects without antibodies (n538), there were no clinically relevant differences in the efficacy of C1-INH concentrate (medians of individual average values: 32 and 24 min for time to onset of symptom relief; 15.5 and 15.4 hours for time to complete resolution of HAE symptoms) or the proportion of subjects experiencing adverse events (47.4% and 42.1%). CONCLUSIONS: There is no indication for the development of inhibitory anti-C1-INH antibodies in subjects treated with C1-INH concentrate for HAE attacks, and the presence of non-inhibitory antibodies does not seem to be of clinical relevance.
complete resolution were considerably faster with 20 U/kg C1-INH vs. _6 hours, HRs for 20 U/ placebo (HRs: 3.36 and 4.30). When treated after > kg C1-INH vs. placebo were substantially reduced for time to onset of symptom relief and complete resolution (1.18 and 1.61). Linear regression also indicated longer times to complete resolution with later treatment. CONCLUSIONS: Early treatment of HAE attacks (<6 hours) with C1INH provides better treatment response than later treatment.
832
Management of paediatric patients with Hereditary Angioedema (HAE)- A retrospective evaluation of 120 patients from 91 families I. Martinez-Saguer, E. Aygoeren-Puersuen, E. Rusicke, T. Klingebiel, W. Kreuz; J.-W. Goethe University Hospital Frankfurt, Germany, Frankfurt, GERMANY. RATIONALE: Although the early manifestations of HAE occur during the initial 2 decades of life, there is limited published experience regarding management of paediatric patients with HAE. METHODS: In a retrospective chart review we evaluated our paediatric patient cohort of 120 patients from 91 families in respect to diagnosis, symptoms presentation and treatment response to human pasteurised C1INH concentrate (BerinertÒ). RESULTS: Our 120 paediatric HAE patients from 91 families at our Frankfurt-CCC have a median age of 10.94 years (range 0.6-17.7 years), female (n562) and male (n558). Observation period was 4.51 years (median, range 0.02-17.6 years). 75 of 120 patients received treatment at first clinical manifestation or for short-term prophylaxis. Nine patients experienced the first HAE attack during the first year of life. The most common localisation of oedema occurred at the extremities, GI tract, urogenital tract, and face. All HAE patients used body-weight adjusted dosing with 20U C1INH/kg BW. Most patients were treated on-demand _ 1 attack/ week individualised replacement (n5 114) and in patients with > therapy (IRT) (n56) was used. Home therapy was practised in 28 patients (24%). Overall, onset of relief was very fast, reliable and treatment was well tolerated. CONCLUSIONS: Early diagnosis is the cornerstone of successful management of HAE in paediatric patients. Body-weight adjusted human pasteurised C1INH concentrate is the first-line therapy for the symptomatic treatment of paediatric HAE patients.
Effect of Time to Treatment on Treatment Response With C1 Esterase-Inhibitor Concentrate (BerinertÒ) for Acute Hereditary Angioedema Attacks J. A. Bernstein1, D. S. Hurewitz2, A. K. Bewtra3, T. Machnig4, H. Keinecke5, T. J. Craig6; 1University of Cincinnati Medical Center and Bernstein Clinical Research Center, Cincinnati, OH, 2Allergy Clinic of Tulsa, Tulsa, OK, 3Creighton University School of Medicine, Omaha, NE, 4CSL Behring GmbH, Marburg, GERMANY, 5Accovion GmbH, Marburg, GERMANY, 6Penn State University, Hershey, PA. RATIONALE: Treatment with C1 esterase-inhibitor (C1-INH) concentrate (BerinertÒ, CSL Behring, Marburg) is well established for hereditary angioedema (HAE) attacks; treatment as early as possible is recommended. To investigate the relationship between time to treatment and treatment response, we conducted a post-hoc analysis of data from the I.M.P.A.C.T studies. _6 hours) METHODS: The relationship between time to treatment (<6 or > and efficacy (times to onset of symptom relief and complete resolution) was evaluated by Cox-regression for I.M.P.A.C.T.1, including hazard ratios (HRs; 10 or 20 U/kg C1-INH or placebo), and by linear regression for I.M.P.A.C.T.2 (20 U/kg C1-INH). HRs >1 indicate higher probabilities for faster relief or resolution with C1-INH vs. placebo. RESULTS: With 20 U/kg C1-INH in I.M.P.A.C.T.1 and I.M.P.A.C.T.2 (per-attack analysis), median times to onset of symptom relief were similar _6 hours (31 and 16 after treatment within 6 hours (30 and 25 min) and > min). Median times to complete resolution were shorter after treatment _6 hours (7.9 and 14.4 within 6 hours (2.8 and 12.6 hours) compared with > hours). After treatment within 6 hours, times to onset of symptom relief and
TUESDAY
831