Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study

V Poletti, C Vancheri, C Albera, S Harari, A Pesci, R R Metella, B Campolo, G Crespi, S Rizzoli, FIBRONET study group, C Vancheri, S Tomassetti, S Harari, A Pesci, C Albera, P Rottoli, M Bocchino, A A Stanziola, F Luppi, A Sebastiani, D Lacedonia, P Vitulo, L Tavanti, A Vianello, M Saetta, S Marinari, P Pirina, S Valente, T Oggionni, S Gasparini, V Poletti, C Vancheri, C Albera, S Harari, A Pesci, R R Metella, B Campolo, G Crespi, S Rizzoli, FIBRONET study group, C Vancheri, S Tomassetti, S Harari, A Pesci, C Albera, P Rottoli, M Bocchino, A A Stanziola, F Luppi, A Sebastiani, D Lacedonia, P Vitulo, L Tavanti, A Vianello, M Saetta, S Marinari, P Pirina, S Valente, T Oggionni, S Gasparini

Abstract

Background: FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF).

Methods: Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted).

Results: 209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study.

Conclusions: FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF.

Trial registration: NCT02803580.

Keywords: Antifibrotic therapy; Idiopathic pulmonary fibrosis; Italy; Lung function; Nintedanib; Observational; Pirfenidone; Real-world.

Conflict of interest statement

BC was an employee of Boehringer Ingelheim (Italy) at the time of this study. GC is an employee of Boehringer Ingelheim. SR is an employee of MediNeos Observational Research (Modena, Italy). AP has received personal (speaker/advisory board) fees from Boehringer Ingelheim and Roche, and his research activity is partially supported by project Premia. SH has acted as a clinical trial investigator, participated in scientific advisory boards, and delivered lectures for Boehringer Ingelheim, Roche and Actelion. He has also received research grants from Boehringer Ingelheim. CA has acted as a clinical trial investigator for Boehringer Ingelheim and Roche, participated in scientific advisory boards for Boehringer Ingelheim, Roche, MSD, Fibrogen and GSK, and received research grants from Boehringer Ingelheim and Roche. CV has received research grants and personal fees from Boehringer Ingelheim and Roche. VP has received personal fees from Boehringer Ingelheim. RRM has nothing to disclose.

Figures

Fig. 1
Fig. 1
FVC% predicted at baseline. Percentages calculated from the total number of evaluable patients with available FVC predicted at baseline (n = 196). FVC forced vital capacity
Fig. 2
Fig. 2
Mean change in FVC% predicted (± SD) during 12 months of observation. FVC forced vital capacity, SD standard deviation

References

    1. Demedts M, Costabel U. ATS/ERS international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Eur Respir J. 2002;19:794–796. doi: 10.1183/09031936.02.00492002.
    1. Travis WD, Costabel U, Hansell DM, King TE, Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188:733–748. doi: 10.1164/rccm.201308-1483ST.
    1. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–e68. doi: 10.1164/rccm.201807-1255ST.
    1. Karimi-Shah BA, Chowdhury BA. Forced vital capacity in idiopathic pulmonary fibrosis–FDA review of pirfenidone and nintedanib. N Engl J Med. 2015;372:1189–1191. doi: 10.1056/NEJMp1500526.
    1. Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute exacerbation and decline in forced vital capacity are associated with increased mortality in idiopathic pulmonary fibrosis. Ann Am Thorac Soc. 2017;14:1395–1402. doi: 10.1513/AnnalsATS.201606-458OC.
    1. Reichmann WM, Yu YF, Macaulay D, Wu EQ, Nathan SD. Change in forced vital capacity and associated subsequent outcomes in patients with newly diagnosed idiopathic pulmonary fibrosis. BMC Pulm Med. 2015;15:167. doi: 10.1186/s12890-015-0161-5.
    1. Kolb M, Richeldi L, Behr J, Maher TM, Tang W, Stowasser S, Hallmann C, du Bois RM. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2017;72:340–346. doi: 10.1136/thoraxjnl-2016-208710.
    1. Fernandez Perez ER, Daniels CE, Schroeder DR, St Sauver J, Hartman TE, Bartholmai BJ, Yi ES, Ryu JH. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137:129–137. doi: 10.1378/chest.09-1002.
    1. Raghu G, Chen SY, Yeh WS, Maroni B, Li Q, Lee YC, Collard HR. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001–11. Lancet Respir Med. 2014;2:566–572. doi: 10.1016/S2213-2600(14)70101-8.
    1. Guenther A, Krauss E, Tello S, Wagner J, Paul B, Kuhn S, Maurer O, Heinemann S, Costabel U, Barbero MAN, et al. The European IPF registry (eurIPFreg): baseline characteristics and survival of patients with idiopathic pulmonary fibrosis. Respir Res. 2018;19:141. doi: 10.1186/s12931-018-0845-5.
    1. Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet J Rare Dis. 2008;3:8. doi: 10.1186/1750-1172-3-8.
    1. Lamas DJ, Kawut SM, Bagiella E, Philip N, Arcasoy SM, Lederer DJ. Delayed access and survival in idiopathic pulmonary fibrosis: a cohort study. Am J Respir Crit Care Med. 2011;184:842–847. doi: 10.1164/rccm.201104-0668OC.
    1. Cosgrove GP, Bianchi P, Danese S, Lederer DJ. Barriers to timely diagnosis of interstitial lung disease in the real world: the INTENSITY survey. BMC Pulm Med. 2018;18:9. doi: 10.1186/s12890-017-0560-x.
    1. Mooney J, Chang E, Lalla D, Papoyan E, Raimundo K, Reddy SR, Stauffer J, Yan T, Broder MS. Potential delays in diagnosis of idiopathic pulmonary fibrosis in medicare beneficiaries. Ann Am Thorac Soc. 2019;16:393–396.
    1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824. doi: 10.1164/rccm.2009-040GL.
    1. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–2082. doi: 10.1056/NEJMoa1402584.
    1. Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE, Jr, Lancaster L, Sahn SA, Szwarcberg J, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377:1760–1769. doi: 10.1016/S0140-6736(11)60405-4.
    1. Maher TM, Molina-Molina M, Russell AM, Bonella F, Jouneau S, Ripamonti E, Axmann J, Vancheri C. Unmet needs in the treatment of idiopathic pulmonary fibrosis-insights from patient chart review in five European countries. BMC Pulm Med. 2017;17:124. doi: 10.1186/s12890-017-0468-5.
    1. Harari S, Madotto F, Caminati A, Conti S, Cesana G. Epidemiology of idiopathic pulmonary fibrosis in Northern Italy. PLoS ONE. 2016;11:e0147072. doi: 10.1371/journal.pone.0147072.
    1. Agabiti N, Porretta MA, Bauleo L, Coppola A, Sergiacomi G, Fusco A, Cavalli F, Zappa MC, Vignarola R, Carlone S, et al. Idiopathic pulmonary fibrosis (IPF) incidence and prevalence in Italy. Sarcoidosis Vasc Diffuse Lung Dis. 2014;31:191–7.
    1. Harari S, Davì M, Biffi A, Caminati A, Ghirardini A, Lovato V, Cricelli C, Lapi F. Epidemiology of idiopathic pulmonary fibrosis: a population-based study in primary care. Intern Emerg Med. 2020;15:437–445. doi: 10.1007/s11739-019-02195-0.
    1. Caminati A, Madotto F, Cesana G, Conti S, Harari S. Epidemiological studies in idiopathic pulmonary fibrosis: pitfalls in methodologies and data interpretation. Eur Respir Rev. 2015;24:436–444. doi: 10.1183/16000617.0040-2015.
    1. Vancheri C, Sebastiani A, Tomassetti S, Pesci A, Rogliani P, Tavanti L, Luppi F, Harari S, Rottoli P, Ghirardini A, et al. Pirfenidone in real life: A retrospective observational multicentre study in Italian patients with idiopathic pulmonary fibrosis. Respir Med. 2019;156:78–84. doi: 10.1016/j.rmed.2019.08.006.
    1. Harari S, Caminati A, Poletti V, Confalonieri M, Gasparini S, Lacedonia D, Luppi F, Pesci A, Sebastiani A, Spagnolo P, et al. A real-life multicenter national study on nintedanib in severe idiopathic pulmonary fibrosis. Respiration. 2018;95:433–440. doi: 10.1159/000487711.
    1. Behr J, Wirtz H, Pittrow D, Prasse A, Koschel D, Geier S, Klotsche J, Andreas S, Claussen M, Grohé C, et al. Survival and course of lung function in patients with idiopathic pulmonary fibrosis with or without antifibrotic treatment: long-term results of the INSIGHTS-IPF registry. Eur Respir J. 2019;54:OA250.
    1. Jo HE, Glaspole I, Grainge C, Goh N, Hopkins PM, Moodley Y, Reynolds PN, Chapman S, Walters EH, Zappala C, et al. Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry. Eur Respir J. 2017;49:1601592. doi: 10.1183/13993003.01592-2016.
    1. Harari S. Randomised controlled trials and real-life studies: two answers for one question. Eur Respir Rev. 2018;27:180080. doi: 10.1183/16000617.0080-2018.
    1. Harari S, Caminati A, Albera C, Vancheri C, Poletti V, Pesci A, Luppi F, Saltini C, Agostini C, Bargagli E, et al. Efficacy of pirfenidone for idiopathic pulmonary fibrosis: an Italian real life study. Respir Med. 2015;109:904–913. doi: 10.1016/j.rmed.2015.04.010.
    1. Flaherty KR, Kolb M, Vancheri C, Tang W, Conoscenti CS, Richeldi L. Stability or improvement in forced vital capacity with nintedanib in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2018;52:pii:1702593. doi: 10.1183/13993003.02593-2017.
    1. Nathan SD, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Glasscock KF, et al. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016;71:429–435. doi: 10.1136/thoraxjnl-2015-207011.
    1. Glaspole IN, Chapman SA, Cooper WA, Ellis SJ, Goh NS, Hopkins PM, Macansh S, Mahar A, Moodley YP, Paul E, et al. Health-related quality of life in idiopathic pulmonary fibrosis: data from the Australian IPF Registry. Respirology. 2017;22:950–956. doi: 10.1111/resp.12989.
    1. Kreuter M, Swigris J, Pittrow D, Geier S, Klotsche J, Prasse A, Wirtz H, Koschel D, Andreas S, Claussen M, et al. The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry. Respir Res. 2019;20:59. doi: 10.1186/s12931-019-1020-3.
    1. Pesonen I, Carlson L, Murgia N, Kaarteenaho R, Sköld CM, Myllärniemi M, Ferrara G. Delay and inequalities in the treatment of idiopathic pulmonary fibrosis: the case of two Nordic countries. Multidiscip Res Med. 2018;13:14. doi: 10.1186/s40248-018-0126-7.
    1. Cottin V, Bergot E, Bourdin A, Cadranel J, Camus P, Crestani B, Dalphin JC, Delaval P, Dromer C, Israel-Biet D, et al. Adherence to guidelines in idiopathic pulmonary fibrosis: a follow-up national survey. ERJ Open Res. 2015;1:00032–02015. doi: 10.1183/23120541.00032-2015.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel