Treatment of idiopathic pulmonary fibrosis with etanercept: An exploratory, placebo-controlled trial

American Journal of Respiratory and Critical Care Medicine

Volumn 178, Issue 9, 2008, Pages 948-955

  Raghu, Ganesh ^a,i   Brown, Kevin K ^b   Costabel, Ulrich ^c   Cottin, Vincent ^d   Du Bois, Roland M ^b   Lasky, Joseph A ^e   Thomeer, Michiel ^f   Utz, James P ^g   Khandker, Rezaul K ^h   McDermott, Lawrence ^h   Fatenejad, Saeed ^h  

^a UNIVERSITY OF WASHINGTON MEDICAL CENTER   (United States)

^b NATIONAL JEWISH MEDICAL AND RESEARCH CENTER   (United States)

^c RUHRLANDKLINIK   (Germany)

^d UNIVERSITÉ LYON 1   (France)

^e TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^f UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^g MAYO CLINIC   (United States)

^h PFIZER INC   (United States)

ⁱ UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Etanercept; Idiopathic pulmonary fibrosis; Placebo controlled; Quality of life; Tumor necrosis factor antagonist

Indexed keywords

ACETYLCYSTEINE; AZATHIOPRINE; CARBON MONOXIDE; COLCHICINE; CORTICOSTEROID DERIVATIVE; CYCLOPHOSPHAMIDE; ETANERCEPT; HEMOGLOBIN; METHOTREXATE; PLACEBO;

ACCIDENTAL INJURY; ADULT; AGED; ARTERIAL OXYGEN TENSION; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; BRONCHITIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; COUGHING; DIARRHEA; DISEASE COURSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DYSPNEA; FEMALE; FIBROSING ALVEOLITIS; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; INJECTION SITE BLEEDING; LUNG DIFFUSION CAPACITY; LUNG FUNCTION; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MYALGIA; NEUTROPENIA; PAIN; PATIENT SATISFACTION; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RASH; RHINITIS; SCORING SYSTEM; SINUSITIS; THORAX PAIN; UPPER RESPIRATORY TRACT INFECTION;

AGED; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CARBON MONOXIDE; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOGLOBULIN G; LUNG; MALE; OXYGEN; PREDICTIVE VALUE OF TESTS; PROSPECTIVE STUDIES; PULMONARY FIBROSIS; QUALITY OF LIFE; RECEPTORS, TUMOR NECROSIS FACTOR; RESEARCH DESIGN; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME; VITAL CAPACITY;

EID: 55549147184     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.200709-1446OC     Document Type: Article

References (50)

1. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161:646-664.
2. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001;345:517-525.
3. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006;174:810-816.
4. Bnà C, Zompatori M, Poletti V, Spaggiari E, Chetta A, Calabrò E, Ormitti F, Berti E, Cancellieri A, Chilosi M. Differential diagnosis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) assessed by high-resolution computed tomography (HRCT). Radiol Med (Torino) 2005;109:472-487.
5. Do KH, Lee JS, Colby TV, Kitaichi M, Kim DS. Nonspecific interstitial pneumonia versus usual interstitial pneumonia: differences in the density histogram of high-resolution CT. J Comput Assist Tomogr 2005;29:544-548.
6. Elliot TL, Lynch DA, Newell JD Jr, Cool C, Tuder R, Markopoulou K, Veve R, Brown KK. High-resolution computed tomography features of nonspecific interstitial pneumonia and usual interstitial pneumonia. J Comput Assist Tomogr 2005;29:339-345.
7. Teirstein AS. The elusive goal of therapy for usual interstitial pneumonia. N Engl J Med 2004;350:181-183.
8. Raghu G. Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based approaches. Eur Respir J 2006;28:463-465.
9. Hunninghake GW. Antioxidant therapy for idiopathic pulmonary fibrosis. N Engl J Med 2005;353:2285-2287.
10. Thrall RS, Vogel SN, Evans R, Shultz LD. Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am J Pathol 1997;151:1303-1310.
11. Johnston CJ, Piedboeuf B, Rubin P, Williams JP, Baggs R, Finkelstein JN. Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation. Radiat Res 1996;145:762-767.
12. Ortiz LA, Lasky J, Hamilton RF Jr, Holian A, Hoyle GW, Banks W, Peschon JJ, Brody AR, Lungarella G, Friedman M. Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. Exp Lung Res 1998;24:721-743.
13. Piguet PF, Ribaux C, Karpuz V, Grau GE, Kapanci Y. Expression and localization of tumor necrosis factor-alpha and its mRNA in idiopathic pulmonary fibrosis. Am J Pathol 1993;143:651-655.
14. Kapanci Y, Desmouliere A, Pache JC, Redard M, Gabbiani G. Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis: possible role of transforming growth factor beta and tumor necrosis factor alpha. Am J Respir Crit Care Med 1995;152:2163-2169.
15. Miyazaki Y, Araki K, Vesin C, Garcia I, Kapanci Y, Whitsett JA, Piguet PF, Vassalli P. Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis: a mouse model of progressive pulmonary fibrosis. J Clin Invest 1995;96:250-259.
16. Sime PJ, Marr RA, Gauldie D, Xing Z, Hewlett BR, Graham FL, Gauldie J, et al. Transfer of tumor necrosis factor-alpha to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factor-beta1 and myofibroblasts. Am J Pathol 1998;153:825-832.
17. Piguet PF, Vesin C. Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice. Eur Respir J 1994;7:515-518.
18. Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993;151:1548-1561.
19. Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586-1593.
20. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martín Mola E, Pavelka K, Sany J, Settas L, et al.; TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) Study Investigators. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675-681.
21. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, Jackson CG, Lange M, Burge DJ. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340:253-259.
22. Brandt J, Khariouzov A, Listing J, Haibel H, Sörensen H, Grassnickel L, Rudwaleit M, Sieper J, Braun J. Six-month results of a doubleblind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 2003;48:1667-1675.
23. Davis JC Jr, van der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W; Enbrel Ankylosing Spondylitis Study Group. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 2003;48:3230-3236.
24. Calin A, Dijkmans BA, Emery P, Hakala M, Kalden J, Leirisalo-Repo M, Mola EM, Salvarani C, Sanmartí R, Sany J, et al. Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis 2004;63:1594-1600.
25. Davis JC, van der Heijde DM, Braun J, Dougados M, Cush J, Clegg D, Inman RD, Kivitz A, Zhou L, Solinger A, et al. Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks. Ann Rheum Dis 2005;64:1557-1562.
26. Mease PJ, Goffe BS, Metz J, Vanderstoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356:385-390.
27. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, Salonen D, Rubenstein J, Sharp JT, Tsuji W. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;50:2264-2272.
28. Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, Gottlieb AB; Etanercept Psoriasis Study Group. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349:2014-2022.
29. Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, Gaspari AA, Ling M, Weinstein GD, Nayak A, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 2003;139:1627-1632. [Discussion, p. 1632.]
30. Raghu G, Lasky JA, Costabel U, Brown KK, Cottin V, Thomeer M, Utz J, McDermott L. Randomized placebo controlled trial assessing the efficacy and safety of etanercept in patients with idiopathic pulmonary fibrosis [abstract]. Chest 2005;128:496S.
31. Raghu G, McDermott L, Khandker R. St. George's Respiratory Questionnaire (SGRQ) for assessing quality of life (QOL) in patients with idiopathic pulmonary fibrosis (IPF) [abstract]. Am J Respir Crit Care Med 2007;176:A144.
32. Raghu G, Fatenejad S, McDermott L. Efficacy and safety of etanercept in patients with idiopathic pulmonary fibrosis (IPF). Eur Respir J 2006;28:767S.
33. Immunex Corporation. Enbrel (etanercept) prescribing information. Thousand Oaks, CA: Immunex Corporation; 2006.
34. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;123:659-664.
35. Jones PW, Spencer S, Adi S. The St George's Respiratory Questionnaire manual, version 2.1. ed. London, UK: St George's Hospital, 2003.
36. Lynch DA, David Godwin J, Safrin S, Starko KM, Hormel P, Brown KK, Raghu G, King TE Jr, Bradford WZ, Schwartz DA, et al.; Idiopathic Pulmonary Fibrosis Study Group. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005;172:488-493.
37. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988;75:800-802.
38. Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med 1999;341:1264-1269.
39. National Cancer Institute. Common terminology criteria for adverse events. Vol. 3. Glossary of terms [Internet] [accessed 2007 Jul 22]. Cancer Therapy Evaluation Program. Bethesda, MD: National Institutes of Health; 2003. Available from: http://ctep.cancer.gov/forms/CTCAE_Glossary.pdf.
40. Demedts M, Behr J Buhl R, Costabel U, Dekhuijzen R, Jansen HM, MacNee W, Thomeer M, Wallaert B, Laurent F, Nicholson AG, et al.; IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2005;353:2229-2242.
41. King TE Jr, Behr J, Brown KK, du Bois RM, Lancaster L, de Andrade JA, Stähler G, Leconte I, Roux S, Raghu G. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008;177:75-81.
42. Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, et al. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168:543-548.
43. Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, et al.; IPF Study Group. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005;142:963-967.
44. Latsi PI, du Bois RM, Nicholson AG, Colby TV, Bisirtzoglou D, Nikolakopoulou A, Veeraraghavan S, Hansell DM, Wells AU. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am J Respir Crit Care Med 2003;168:531-537.
45. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, et al.; Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007;176:636-643.
46. Johnson WC, Raghu G. Clinical trials in idiopathic pulmonary fibrosis: a word of caution concerning choice of outcome measures. Eur Respir J 2005;26:755-758.
47. Eaton T, Young P, Milne D, Wells AU. Six-minute walk, maximal exercise tests: reproducibility in fibrotic interstitial pneumonia. Am J Respir Crit Care Med 2005;171:1150-1157.
48. Ostör AJ, Chilvers ER, Somerville MF, Lim AY, Lane SE, Crisp AJ, Scott DG. Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. J Rheumatol 2006;33:622-628.
49. Villeneuve E, St-Pierre A, Haraoui B. Interstitial pneumonitis associated with infliximab therapy. J Rheumatol 2006;33:1189-1193.
50. Raghu G, Brown KK, Bradford WZ, Starko K, Noble PW, Schwartz DA, King TE Jr; Idiopathic Pulmonary Fibrosis Study Group. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 2004;350:125-133.