Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study
Authors: Jovanovic Dragana M. , Šterclová Martina , Mogulkoc Nesrin , Lewandowska Katarzyna , Müller Veronika , Hájková Marta , Studnicka Michael , Tekavec-Trkanjec Jasna , Littnerová Simona , Vašáková Martina ,   the EMPIRE registry investigators, Zembacher Stefan , Studnicka Michael , Lang David , Lamprecht Bernd , Stoeva Natalia , Mladinov Suzana , Ilak Dino , Vergles Mirna , Tudorić Neven , Tekavec-Trkanjec Jasna , Vašáková Martina , Šterclová Martina , Jiří  , Lacina Ladislav , Lisá Pavlína , Bittenglová Radka , Bartoš Vladimír , Renata  , Lošťáková Vladimíra , Žurková Monika , Pšíkalová Jana , Binková Ilona , Doubková Martina , Kervitzer Jan , Snížek Tomáš , Reiterer Pavel , Šuldová Hana , Plačková Martina , Tyl Richard , Řihák Vladimír , Dušek Ladislav , Hejduk Karel , Gregor Jakub , Májek Ondřej , Littnerová Simona , Svoboda Michal , Zsiray Miklós , Müller Veronika , Bohács Anikó , Szilasi Maria , Szalai Zsuzsanna , Balikó Zoltán , Somfay Attila , Lajkó Imre , Kramer Mordechai , Adir Yochai , Kjaeva Biserka Jovkovska , Jassem Ewa , Sieminska Alicja , Szymanowska-Narloch Amelia , Barczyk Adam , Sladek Krzysztof , Kania Aleksander , Kasper Lukasz , Stachura Tomasz , Jurek Paulina , Majewski Sebastian , Nowicka Agata , Borucki Lukasz , Lewandowska Katarzyna , Sobiecka Małgorzata , Zolnowska Beate , Sliwinski Pawel , Korzybski Damian , Martusewicz-Boros Magdalena , Wiatr Elzbieta , Maskey-Warzęchowska Marta , Górska Katarzyna , Barnaś Małgorzata , Vučinić-Mihailović Violeta , Milenković Branislava , Kontić Milica , Samardžić Natalija , Roksandić Marina , Jovanovic Dragana , Pejcic Tatjana , Boravac Desa Nastasijevic , Videnovic Emilija , Petkovic Tatjana Radjenovic , Djordejevic Ivanka , Lečić Svetlana Kašiković , Kuruc Vesna , Eri Živka , Panjković Milana , Lovrenski Aleksandra , Kukavica Darinka , Jakić Ana , Mojsilovic Slavica , Hájková Marta , Laššán Štefan , Tóth Štefan , Plutinský Ján , Vyšehradský Róbert , Matula Bohumil , Slivka Róbert , Jonner Imrich , Mogulkoc Nesrin 
Published: May 2022

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.