Sex influence on outcomes of patients with systemic sclerosis–associated interstitial lung disease: a EUSTAR database analysis
Authors: Campochiaro Corrado , Hoffmann-Vold Anna-Maria , Avouac Jerome , Henes Jörg , de Vries-Bouwstra Jeska , Smith Vanessa , Siegert Elise , Airò Paolo , Oksel Fahrettin , Pellerito Raffaele , Vanthuyne Marie , Pozzi Maria Rosa , Inanc Murat , Sibilia Jean , Gabrielli Armando , Distler Oliver , Allanore Yannick ,   EUSTAR Collaborators, Cerinic Marco Matucci , Walker Ulrich , Iannone Florenzo , Becvar Radim , Cuomo Giovanna , Montecucco C , Carreira Patricia E , Iudici Michele , Kucharz Eugene J , Zanatta Elisabetta , Bancel Pr Dominique Farge , Hesselstrand Roger , Balbir-Gurman Alexandra , Pellerito Raffaele , Bertoldo Eugenia , Damjanov Nemanja , Granollers Vera Ortiz-Santamaria , Heitmann Stefan , Salvador Maria João , Stamenkovic Bojana , Selmi Carlo Francesco , Herrick Ariane , ller-Ladner Ulf Mü , Engelhart Merete , Riccieri Valeria , Ionescu Ruxandra Maria , Gheorghiu Ana Maria , Sunderkötter Cord , Distler Jörg , Ingegnoli Francesca , Mouthon Luc , Cantatore Francesco Paolo , Ullman Susanne , Wiland Piotr , Vanthuyne Marie , Saar Petra , Herrmann Kristine , De Langhe Ellen , Mayer Miroslav , Yavuz Sule , de Souza Müller Carolina , Zenone Thierry , Vacca Alessandra , Solanki Kamal , Rosato Edoardo , Yargucu Fahrettin Oksel Figen , Tanaseanu Cristina-Mihaela , Foti Rosario , Furst Daniel E , Adler Peter Villiger Sabine , Martín Jorge Juan González , Litinsky Ira , Del Galdo Francesco , Seskute Goda , Saketkoo Lesley Ann , Kerzberg Eduardo , Castellví Ivan , Spertini François , Hsu Vivien M , Martin Thierry , Schmeiser Tim , Majewski Dominik , Bernardino Vera , Puttini Piercarlo Sarzi , Moroncini Gianluca , Stork Jiri , Hachulla Eric , de la Pena Lefebvre Paloma Garcıa , Limonta Massimiliano , Sfikakis Petros , Cutolo Maurizio , Ananieva Lidia P , Czirjak Laszlo , Denton Christopher , De Luca Giacomo , Dagna Lorenzo 
Published: November 2022

Abstract

Objective
Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD.

Methods
EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s.d. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s.d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied.

Results
A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P &lt; 0.001). In the survival analysis, male sex was a predictor of mortality [OR 1.95 (95% CI 1.66, 2.28)].

Conclusions
Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD.