Interferon Alfacon-1 Plus Corticosteroids in Severe Acute Respiratory Syndrome

A Preliminary Study

Loutfy, Mona R. MD, MPH
Blatt, Lawrence M. PhD
Siminovitch, Katharine A. MD
Ward, Sarah BSc
Wolff, Bryan MD
Lho, Hyoung MD
Pham, Dieu H. MD
Deif, Hassan MD
LaMere, Elizabeth A. MD
Chang, Margaret MD
Kain, Kevin C. MD
Farcas, Gabriella A. BSc
Ferguson, Patti BScPhm
Latchford, Mary BSc, MLT
Levy, Gary MD
Dennis, James W. PhD
Lai, Enoch K. Y. MD
Fish, Eleanor N. PhD

North York General Hospital (Drs Loutfy, Wolff, Lho, Pham, Deif, LaMere, Chang, and Lai and Mss Ferguson and Latchford), Toronto General Research Institute and University of Toronto (Drs Siminovitch, Kain, Levy, and Fish and Mss Ward and Farcas), and Mt Sinai Hospital and University of Toronto (Dr Dennis), Toronto, Ontario; and Intermune Corp, Brisbane, Calif (Dr Blatt).

Corresponding Author and Reprints: Eleanor N. Fish, PhD, Division of Cell and Molecular Biology, Toronto General Research Institute, Canadian Blood Services Bldg, Room 424, 67 College St, Toronto, Ontario, Canada M5G 2M1 (e-mail: [email protected]).

Author Contributions: Dr Fish had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Loutfy, Blatt, Fish.

Acquisition of data: Loutfy, Blatt, Siminovitch, Ward, Wolff, Lho, Deif, LaMere, Chang, Kain, Farcas, Ferguson, Latchford, Lai, Fish.

Analysis and interpretation of data: Loutfy, Blatt, Siminovitch, Ward, Pham, Deif, Lai, Fish.

Drafting of the manuscript: Loutfy, Blatt, Siminovitch, Ward, Wolff, Lho, Pham, Deif, Chang, Kain, Latchford, Dennis, Lai, Fish.

Critical revision of the manuscript for important intellectual content: Loutfy, Blatt, Siminovitch, Fish.

Statistical expertise: Loutfy, Blatt, Fish.

Obtained funding: Siminovitch, Dennis, Fish.

Administrative, technical, or material support: Blatt, Siminovitch, Ward, Lho, Pham, Deif, LaMere, Chang, Kain, Farcas, Ferguson, Latchford, Fish.

Study supervision: Loutfy, Blatt, Fish.

Funding/Support: This work was funded by a grant from the Canadian Institutes of Health Research (CIHR) and Ontario Research and Development Challenge Fund (ORDCF) to Drs Siminovitch, Dennis, and Fish. Intermune Corp provided the interferon alfacon-1 at no cost. Dr Kain holds a Canada Research Chair, Dr Loutfy is a CIHR postdoctoral fellow (McGill University, Montreal, Quebec), and Dr Siminovitch is a CIHR senior scientist.

Role of the Sponsor: The CIHR and the ORDCF did not contribute in any way to the design and conduct of the study, to the collection, analysis, and interpretation of the data, or to the preparation, review, or approval of the manuscript.

Acknowledgment: We dedicate this article to the memory of Nelia Laroza, a colleague from NYGH who succumbed to SARS. We are grateful to Barbara Mederski, MD, for enabling access to patients at NYGH and to Chris Chalmers, PharmD (Intermune Corp), for expediting the special access program for release of interferon alfacon-1.

JAMA: The Journal of the American Medical Association 290(24):p 3222-3228, December 24/31, 2003.

Context

Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed.

Objective

To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS.

Design, Setting, and Patients

Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003.

Interventions

Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1.

Main Outcome Measures

Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results.

Results

Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better oxygen saturation (P =.02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine kinase levels (P =.03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone.

Conclusions

In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.