A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma

I. Leonard Bernstein, David I. Bernstein, Jeffrey W. Dubb, Isidore Faiferman, Bruce Wallin, Edwin Bronsky, Sheldon L. Spector, Robert A. Nathan, Harold S. Nelson, Emil J. Bardana, Malcolm N. Blumenthal, Roger C. Bone, Dick D. Briggs, William W. Busse, Samuel C. Campbell, John J. Condemi, M. R. Crain, Jay Grossman, George J. Handley, James P. Kemp & 16 others William B. Klaustermeyer, Dennis K. Ledford, Richard F. Lockey, Manuel Lopez, Donald L. McNeil, W. James Metzger, Anthony Montanaro, Jacob L. Pinnas, Mark F. Sands, William F. Schoenwetter, Robert G. Townley, Martin D. Valentine, Paul P. Van Arsdel, Andras J. Vari, Stephen C. Weisberg, Howard J. Zeitz

Research output: Contribution to journalArticle

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Abstract

Background: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. Objectives: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. Methods: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≤ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase 1), a 6-month double- blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was 'therapeutic success' or reduction of daily corticosteroid use by 50% or more. Results: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p <0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (≤50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p <0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. Conclusions: Auranofin demonstrated a steroid- sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid- dependent asthma.

Original languageEnglish
Pages (from-to)317-324
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume98
Issue number2
StatePublished - 1996
Externally publishedYes

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Auranofin
Multicenter Studies
Adrenal Cortex Hormones
Asthma
Placebos
Steroids
Prednisone
Therapeutics
Gold Compounds
Lung
Gold
Immunoglobulin E

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Bernstein, I. L., Bernstein, D. I., Dubb, J. W., Faiferman, I., Wallin, B., Bronsky, E., ... Zeitz, H. J. (1996). A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Journal of Allergy and Clinical Immunology, 98(2), 317-324.

A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. / Bernstein, I. Leonard; Bernstein, David I.; Dubb, Jeffrey W.; Faiferman, Isidore; Wallin, Bruce; Bronsky, Edwin; Spector, Sheldon L.; Nathan, Robert A.; Nelson, Harold S.; Bardana, Emil J.; Blumenthal, Malcolm N.; Bone, Roger C.; Briggs, Dick D.; Busse, William W.; Campbell, Samuel C.; Condemi, John J.; Crain, M. R.; Grossman, Jay; Handley, George J.; Kemp, James P.; Klaustermeyer, William B.; Ledford, Dennis K.; Lockey, Richard F.; Lopez, Manuel; McNeil, Donald L.; Metzger, W. James; Montanaro, Anthony; Pinnas, Jacob L.; Sands, Mark F.; Schoenwetter, William F.; Townley, Robert G.; Valentine, Martin D.; Van Arsdel, Paul P.; Vari, Andras J.; Weisberg, Stephen C.; Zeitz, Howard J.

In: Journal of Allergy and Clinical Immunology, Vol. 98, No. 2, 1996, p. 317-324.

Research output: Contribution to journalArticle

Bernstein, IL, Bernstein, DI, Dubb, JW, Faiferman, I, Wallin, B, Bronsky, E, Spector, SL, Nathan, RA, Nelson, HS, Bardana, EJ, Blumenthal, MN, Bone, RC, Briggs, DD, Busse, WW, Campbell, SC, Condemi, JJ, Crain, MR, Grossman, J, Handley, GJ, Kemp, JP, Klaustermeyer, WB, Ledford, DK, Lockey, RF, Lopez, M, McNeil, DL, Metzger, WJ, Montanaro, A, Pinnas, JL, Sands, MF, Schoenwetter, WF, Townley, RG, Valentine, MD, Van Arsdel, PP, Vari, AJ, Weisberg, SC & Zeitz, HJ 1996, 'A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma', Journal of Allergy and Clinical Immunology, vol. 98, no. 2, pp. 317-324.
Bernstein, I. Leonard ; Bernstein, David I. ; Dubb, Jeffrey W. ; Faiferman, Isidore ; Wallin, Bruce ; Bronsky, Edwin ; Spector, Sheldon L. ; Nathan, Robert A. ; Nelson, Harold S. ; Bardana, Emil J. ; Blumenthal, Malcolm N. ; Bone, Roger C. ; Briggs, Dick D. ; Busse, William W. ; Campbell, Samuel C. ; Condemi, John J. ; Crain, M. R. ; Grossman, Jay ; Handley, George J. ; Kemp, James P. ; Klaustermeyer, William B. ; Ledford, Dennis K. ; Lockey, Richard F. ; Lopez, Manuel ; McNeil, Donald L. ; Metzger, W. James ; Montanaro, Anthony ; Pinnas, Jacob L. ; Sands, Mark F. ; Schoenwetter, William F. ; Townley, Robert G. ; Valentine, Martin D. ; Van Arsdel, Paul P. ; Vari, Andras J. ; Weisberg, Stephen C. ; Zeitz, Howard J. / A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. In: Journal of Allergy and Clinical Immunology. 1996 ; Vol. 98, No. 2. pp. 317-324.
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title = "A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma",
abstract = "Background: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. Objectives: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. Methods: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≤ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase 1), a 6-month double- blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was 'therapeutic success' or reduction of daily corticosteroid use by 50{\%} or more. Results: The proportion of patients in the auranofin group achieving therapeutic success (41{\%}) was significantly higher than that in the placebo group (27{\%}) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p <0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (≤50{\%} of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60{\%}) compared with the placebo group (32{\%}) (p <0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. Conclusions: Auranofin demonstrated a steroid- sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid- dependent asthma.",
author = "Bernstein, {I. Leonard} and Bernstein, {David I.} and Dubb, {Jeffrey W.} and Isidore Faiferman and Bruce Wallin and Edwin Bronsky and Spector, {Sheldon L.} and Nathan, {Robert A.} and Nelson, {Harold S.} and Bardana, {Emil J.} and Blumenthal, {Malcolm N.} and Bone, {Roger C.} and Briggs, {Dick D.} and Busse, {William W.} and Campbell, {Samuel C.} and Condemi, {John J.} and Crain, {M. R.} and Jay Grossman and Handley, {George J.} and Kemp, {James P.} and Klaustermeyer, {William B.} and Ledford, {Dennis K.} and Lockey, {Richard F.} and Manuel Lopez and McNeil, {Donald L.} and Metzger, {W. James} and Anthony Montanaro and Pinnas, {Jacob L.} and Sands, {Mark F.} and Schoenwetter, {William F.} and Townley, {Robert G.} and Valentine, {Martin D.} and {Van Arsdel}, {Paul P.} and Vari, {Andras J.} and Weisberg, {Stephen C.} and Zeitz, {Howard J.}",
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TY - JOUR

T1 - A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma

AU - Bernstein, I. Leonard

AU - Bernstein, David I.

AU - Dubb, Jeffrey W.

AU - Faiferman, Isidore

AU - Wallin, Bruce

AU - Bronsky, Edwin

AU - Spector, Sheldon L.

AU - Nathan, Robert A.

AU - Nelson, Harold S.

AU - Bardana, Emil J.

AU - Blumenthal, Malcolm N.

AU - Bone, Roger C.

AU - Briggs, Dick D.

AU - Busse, William W.

AU - Campbell, Samuel C.

AU - Condemi, John J.

AU - Crain, M. R.

AU - Grossman, Jay

AU - Handley, George J.

AU - Kemp, James P.

AU - Klaustermeyer, William B.

AU - Ledford, Dennis K.

AU - Lockey, Richard F.

AU - Lopez, Manuel

AU - McNeil, Donald L.

AU - Metzger, W. James

AU - Montanaro, Anthony

AU - Pinnas, Jacob L.

AU - Sands, Mark F.

AU - Schoenwetter, William F.

AU - Townley, Robert G.

AU - Valentine, Martin D.

AU - Van Arsdel, Paul P.

AU - Vari, Andras J.

AU - Weisberg, Stephen C.

AU - Zeitz, Howard J.

PY - 1996

Y1 - 1996

N2 - Background: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. Objectives: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. Methods: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≤ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase 1), a 6-month double- blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was 'therapeutic success' or reduction of daily corticosteroid use by 50% or more. Results: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p <0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (≤50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p <0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. Conclusions: Auranofin demonstrated a steroid- sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid- dependent asthma.

AB - Background: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. Objectives: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. Methods: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≤ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase 1), a 6-month double- blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was 'therapeutic success' or reduction of daily corticosteroid use by 50% or more. Results: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p <0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (≤50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p <0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. Conclusions: Auranofin demonstrated a steroid- sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid- dependent asthma.

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