To convene a diverse panel of physicians to formally review available data on treatment options for idiopathic pulmonary fibrosis (IPF) and to rate the “appropriateness,” “inappropriateness,” or “uncertainty” of some of the available therapeutic options.
A formal literature review was conducted on the risks and benefits of commonly used treatment options for IPF. The Medline and Cochrane databases were searched through September 2003, and supplemental information was obtained from specialty societies, pharmaceutical companies, and investigators. Unpublished, pertinent and new data from a just completed clinical trial presented at a recent international society meeting was included in abstract form. The panel comprised nine selected physicians from geographically diverse areas who practiced in community-based settings and academic institutions. The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the treatment of IPF. The consensus method did not force agreement.
Please see Table 1Table 1.
Appropriateness of various treatments for IPF by age and severity subgroups.No TreatmentSteroids aloneAzathioprine + SteroidsCyclophos + SteroidsIFNIFN + Steroids<65, mildNo prior steroids or cytotoxic agents––+000*Failed prior steroids––+0+0Failed prior cytotoxic agents––0–++Failed prior steroids and cytotoxic agents0*–––++<65, moderateNo prior steroids or cytotoxic agents––+00*0*Failed prior steroids––00+0Failed prior cytotoxic agents––0–++Failed prior steroids and cytotoxic agents––––++<65, severeNo prior steroids or cytotoxic agents––00–0Failed prior steroids––000*0Failed prior cytotoxic agents0*–––0*0Failed prior steroids and cytotoxic agents0*–––0*065-79, mildNo prior steroids or cytotoxic agents––0–00*Failed prior steroids0–0*–+0Failed prior cytotoxic agents0*–––00Failed prior steroids and cytotoxic agents0*–––+065-79, moderateNo prior steroids or cytotoxic agents––0–00*Failed prior steroids––0*–+0Failed prior cytotoxic agents0*–––+0Failed prior steroids and cytotoxic agents0*–––+065-79, severeNo prior steroids or cytotoxic agents0*–0*–––Failed prior steroids0*–0*––0Failed prior cytotoxic agents0*––––0Failed prior steroids and cytotoxic agents0*–––00*0 = panelist disagreement+ = Appropriate, –= Inappropriate, 0 = Uncertain, Steroids = Corticosteroids, Cyclophos = Cyclophosphamide*0 = panelist disagreement
+ = Appropriate, - = Inappropriate, 0 = Uncertain, Steroids = Corticosteroids, Cyclophos = Cyclophosphamide.
The panel concluded that corticosteroids alone are always “inappropriate.” Cyclophosphamide plus steroids are “inappropriate” for those aged 65-79 and “uncertain” as initial therapy for those under 65. Azathioprine plus steroids are “appropriate” as initial therapy in those under 65 (unless they showed signs of severe objective impairment when it was “uncertain”), and “uncertain” as initial therapy in those 65-79. Interferon gamma is “appropriate” for patients who have failed initial therapy with either steroids or cytotoxic agents and have mild to moderate objective impairment, “uncertain” as initial therapy, and “inappropriate” as initial therapy in patients with severe objective impairment. The appropriateness of pirfenidone is “uncertain” in all scenarios. Providing no therapy is “inappropriate” for most scenarios. Referring patients for enrollment in randomized trials is “appropriate” in all scenarios. Referring patients for transplant evaluation is “appropriate” for patients under 65 and “inappropriate” for those over 65.
In patients with known IPF, the use of corticosteroids alone is inappropriate, referral for enrollment in randomized trials should be strongly considered, and patients under 65 should be referred for transplant evaluation. Table 2.
Consensus Panel Members for: A critical assessment of treatment options for idiopathic pulmonary fibrosis. This work was supported by an unrestricted grant from the Coalition for Pulmonary Fibrosis (CPF). The Coalition did not play any role in the design or conduct of the study, in the collection, analysis or interpretation of the data, or the preparation of the manuscript. The majority of the authors have received honoraria from companies that manufacture and distribute therapies mentioned in this report; several also serve as consultants and are on the advisory board and steering committee for clinical trials sponsored by pharmaceutical companies, received honoraria for giving lectures sponsored by InterMune, Inc. and are on the Board for the CPF.Panel MembersInstitutionsPaul Noble, MD11Yale University School of Medicine Department of Internal Medicine, New Haven, CTRobert M. Jackson, MD22University of Alabama at Birmingham, Birmingham, ALTalmadge E. King, Jr., MD33Department of Medicine, University of California San Francisco, San Francisco, CASteven D. Nathan, MD44Inova Fairfax Hospital, Falls Church, VAMaria Padilla, MD55North Shore University Medical Center, Manhasset, NYGanesh Raghu, MD66Department of Medicine, University of Washington, Seattle, WAMelissa Bruce Rhodes, MD77Georgia Lung Associates, Austell, GAMarvin Schwarz, MD88University of Colorado Health Sciences Center, Denver, COGregory Tino, MD99University of Pennsylvania Medical Center, Philadelphia, PA
N.R. Shah, None.