Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study
Dragana Jovanović, Martina Šterclová, Nesrin Moğulkoç, Katarzyna Lewandowska, Veronika Müller, Marta Hájková, Michael Studnicka, Jasna Tekavec-Trkanjec, Simona Littnerová, Martina Vašáková, the EMPIRE registry investigators, Stefan Zembacher, Michael Studnicka, David Lang, Bernd Lamprecht, Natalia Stoeva, Suzana Mladinov, Dino Ilak, Mirna Vergles, Neven Tudorić, Jasna Tekavec-Trkanjec, Martina Vašáková, Martina Šterclová, Jiří, Ladislav Lacina, Pavlína Lisá, Radka Bittenglová, Vladimı́r Bartoš, Renata, Vladimíra Lošťáková, Monika Žůrková, Jana Pšíkalová, Ilona Binková, Martina Doubková, Jan Kervitzer, Tomáš Snížek, Pavel Reiterer, Hana Šuldová, Martina Plačková, Richard Tyl, Vladimír Řihák, Ladislav Dušek, Karel Hejduk, Jakub Gregor, Ondřej Májek, Simona Littnerová, Michal Svoboda, Miklós Zsiray, Veronika Müller, Anikó Bohács, Mária Szilasi, Zsuzsanna Szalai, Zoltán Balikó, Attila Somfay, Imre Lajkó, Mordechai R Kramer, Yochai Adir, Biserka Jovkovska Kjaeva, Ewa Jassem, Alicja Siemińska, Amelia Szymanowska-Narloch, Adam Barczyk, Krzysztof Sładek, Aleksander Kania, Łukasz Kasper, Tomasz Stachura, Paulina Jurek, Sebastian Majewski, Agata Nowicka, Łukasz Borucki, Katarzyna Lewandowska, Małgorzata Sobiecka, Beate Zolnowska, Paweł Śliwiński, Damian Korzybski, Magdalena Martusewicz-Boros, Elżbieta Wiatr, Marta Maskey‐Warzęchowska, Katarzyna Górska, Małgorzata Barnaś, Violeta Vučinić-Mihailović, Branislava Milenković, Milica Kontić, Natalija Samardžić, Marina Roksandić, Dragana Jovanović, Tatjana Pejčić, Desa Nastasijevic Boravac, Emilija Videnovic, Tatjana Petković, Ivanka Djordejevic, Svetlana Kašiković-Lečić, Vesna Kuruc, Živka Eri, Milana Panjković, Aleksandra Lovrenski, Darinka Kukavica, Ana Jakić, Slavica Mojsilović, Marta Hájková
Abstract
BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry. METHODS: For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment. RESULTS: A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths. CONCLUSIONS: The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.