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Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

Abstract Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a 2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients), in two administrations 14 days apart. Patients assigned to lanadelumab were enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4 patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic profile of lanadelumab was assessed by measurement of plasma levels of cleaved high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and 400-mg groups as compared with the placebo group. Results No discontinuations occurred because of adverse events, serious adverse events, or deaths in patients who received lanadelumab. The most common adverse events that emerged during treatment were attacks of angioedema, injection-site pain, and headache. Dose-proportional increases in serum concentrations of lanadelumab were observed; the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma from patients with hereditary angioedema with C1 inhibitor deficiency to levels approaching that from patients without the disorder. From day 8 to day 50, the 300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg group were attack-free, as compared with 27% (3 of 11) in the placebo group. Conclusions In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).
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Journal Title the new england journal of medicine
Publication Year Start




PMID- 28225674
OWN - NLM
STAT- In-Data-Review
DA  - 20170222
LR  - 20170222
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 376
IP  - 8
DP  - 2017 Feb 23
TI  - Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.
PG  - 717-728
LID - 10.1056/NEJMoa1605767 [doi]
AB  - Background Hereditary angioedema with C1 inhibitor deficiency is characterized by
      recurrent, unpredictable swelling episodes caused by uncontrolled plasma
      kallikrein generation and excessive bradykinin release resulting from cleavage of
      high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein
      inhibitor with the potential for prophylactic treatment of hereditary angioedema 
      with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter,
      double-blind, placebo-controlled, multiple-ascending-dose trial. Patients with
      hereditary angioedema with C1 inhibitor deficiency were randomly assigned in a
      2:1 ratio to receive either lanadelumab (24 patients) or placebo (13 patients),
      in two administrations 14 days apart. Patients assigned to lanadelumab were
      enrolled in sequential dose groups: total dose of 30 mg (4 patients), 100 mg (4
      patients), 300 mg (5 patients), or 400 mg (11 patients). The pharmacodynamic
      profile of lanadelumab was assessed by measurement of plasma levels of cleaved
      high-molecular-weight kininogen, and efficacy was assessed by the rate of attacks
      of angioedema during a prespecified period (day 8 to day 50) in the 300-mg and
      400-mg groups as compared with the placebo group. Results No discontinuations
      occurred because of adverse events, serious adverse events, or deaths in patients
      who received lanadelumab. The most common adverse events that emerged during
      treatment were attacks of angioedema, injection-site pain, and headache.
      Dose-proportional increases in serum concentrations of lanadelumab were observed;
      the mean elimination half-life was approximately 2 weeks. Lanadelumab at a dose
      of 300 mg or 400 mg reduced cleavage of high-molecular-weight kininogen in plasma
      from patients with hereditary angioedema with C1 inhibitor deficiency to levels
      approaching that from patients without the disorder. From day 8 to day 50, the
      300-mg and 400-mg groups had 100% and 88% fewer attacks, respectively, than the
      placebo group. All patients in the 300-mg group and 82% (9 of 11) in the 400-mg
      group were attack-free, as compared with 27% (3 of 11) in the placebo group.
      Conclusions In this small trial, administration of lanadelumab to patients with
      hereditary angioedema with C1 inhibitor deficiency reduced cleavage of
      high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax;
      ClinicalTrials.gov number, NCT02093923 .).
FAU - Banerji, Aleena
AU  - Banerji A
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Busse, Paula
AU  - Busse P
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Shennak, Mustafa
AU  - Shennak M
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Lumry, William
AU  - Lumry W
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Davis-Lorton, Mark
AU  - Davis-Lorton M
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Wedner, Henry J
AU  - Wedner HJ
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Jacobs, Joshua
AU  - Jacobs J
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Baker, James
AU  - Baker J
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Bernstein, Jonathan A
AU  - Bernstein JA
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Lockey, Richard
AU  - Lockey R
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Li, H Henry
AU  - Li HH
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Craig, Timothy
AU  - Craig T
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Cicardi, Marco
AU  - Cicardi M
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Riedl, Marc
AU  - Riedl M
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Al-Ghazawi, Ahmad
AU  - Al-Ghazawi A
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Soo, Carolyn
AU  - Soo C
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Iarrobino, Ryan
AU  - Iarrobino R
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Sexton, Daniel J
AU  - Sexton DJ
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - TenHoor, Christopher
AU  - TenHoor C
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Kenniston, Jon A
AU  - Kenniston JA
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Faucette, Ryan
AU  - Faucette R
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Still, J Gordon
AU  - Still JG
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Kushner, Harvey
AU  - Kushner H
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Mensah, Robert
AU  - Mensah R
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Stevens, Chris
AU  - Stevens C
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Biedenkapp, Joseph C
AU  - Biedenkapp JC
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Chyung, Yung
AU  - Chyung Y
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
FAU - Adelman, Burt
AU  - Adelman B
AD  - From the Division of Rheumatology, Allergy, and Immunology, Department of
      Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (A.B.), 
      Dyax, Burlington (C. Soo, R.I., D.J.S., C.T., J.A.K., R.F., H.K., R.M., C.
      Stevens, J.C.B., Y.C., B.A.), and ICON Clinical Research, Marlborough (J.G.S.) - 
      all in Massachusetts; the Division of Clinical Immunology and Allergy, Department
      of Medicine, Icahn School of Medicine at Mount Sinai, New York (P.B.), and
      Winthrop University Hospital, Mineola (M.D.-L.) - both in New York; Triumpharma, 
      Amman, Jordan (M.S., A.A.-G.); Asthma and Allergy Research Associates, Dallas
      (W.L.); the Division of Allergy and Immunology, Washington University School of
      Medicine, St. Louis (H.J.W.); Allergy and Asthma Medical Group, Walnut Creek
      (J.J.), and the Department of Rheumatology, Allergy, and Immunology, University
      of California, San Diego, San Diego (M.R.) - both in California; Baker Allergy,
      Asthma, and Dermatology, Lake Oswego, OR (J.B.); the Department of Internal
      Medicine-Allergy Section Cincinnati, University of Cincinnati College of
      Medicine, Cincinnati (J.A.B.); the Division of Allergy and Immunology, Department
      of Internal Medicine, Morsani College of Medicine, University of South Florida,
      Tampa (R.L.); the Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); the
      Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and
      Immunology, Hershey, PA (T.C.); and the Department of Biomedical and Clinical
      Sciences, Luigi Sacco, University of Milan, and Luigi Sacco Hospital Milan, Milan
      (M.C.).
LA  - eng
PT  - Journal Article
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
CRDT- 2017/02/23 06:00
AID - 10.1056/NEJMoa1605767 [doi]
PST - ppublish
SO  - N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767.

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