Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease

Abstract

Objectives: The impact of autoantibody profiles on the prognosis for idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with myositis-specific antibodies (MSAs) remains unclear. This retrospective cohort study examined whether serological profiles were associated with mortality or longitudinal lung function change.

Methods: The baseline clinical/demographic characteristics and follow-up lung function data of consecutive adult patients with IIM-ILD or interstitial pneumonia with autoimmune features (IPAF) positive for MSAs (IPAF-MSA) were extracted from three hospitals. Univariate and multivariate Cox proportional hazards analyses were used to compare mortality between groups of patients with different autoantibodies. Regression models were used to analyse their lung function trends.

Results: Of the 430 included patients, 81% met the IIM criteria, and the remaining 19% were diagnosed with IPAF-MSA. On univariate analysis, the risk factors associated with mortality included higher age, Charlson Comorbidity Index, and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared with anti-MDA5 negativity, anti-MDA5 positivity (MDA5+) was associated with higher mortality in the first 3 months [hazard ratio (HR) 65.2, 95% CI 14.1, 302.0], while no significant difference was seen thereafter (HR 0.55, 95% CI 0.14, 2.28). On multivariate analysis, combined anti-synthetase antibodies were associated with a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in patients with anti-Jo1+ (HR 0.61, 95% CI 0.4-0.87) and increased in patients with anti-PL7+ (HR 2.07, 95% CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards.

Conclusion: Among the autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ conferred higher mortality risks in patients with IIM-ILD. Survivors of an early peak of mortality in anti-MDA5+ disease appeared to have a favourable prognosis.

Keywords: autoantibodies; idiopathic inflammatory myopathies; interstitial lung disease; mortality; myositis; progression.

Figure 1.

Kaplan–Meier curve showing mortality by key antibodies to: MDA-5, PL-7 and Jo-1. This chart demonstrates the number at risk contributing to the analysis for each group in the table below. Early mortality is clearly demonstrated in the anti-MDA5 group

Figure 2.

Hazard ratios for all-cause mortality. Univariate and multivariate models demonstrating hazard ratios and 95% CIs for the primary end point of all-cause mortality according to antibody, vs all other antibodies. The dashed line represents hazard ratio = 1. (A) Unadjusted model (B) Adjusted multivariate model for age, sex, ethnicity, malignancy, clinical CTD overlap status, and hospital site. Anti-MDA5 has been excluded from this figure due to non-proportionality of the hazards

Figure 3.

Trend in FVC over time in (A) MDA-5, (B) PL-7, and (C) Jo1. The data model shows improvement of %pred FVC in anti-MDA5+ compared with anti-MD5–negative patients, which becomes more evident from 2 years onwards, whereas %pred FVC in anti-PL7+ patients appears lower than in anti-PL7–negative patients. The anti-Jo1+ pattern of %pred FVC over time does not appear to differ from that of anti-Jo1–negative patients. FVC: FVC: forced vital capacity; %pred: percentage of predicted value