Malignancy in anti-synthetase syndrome: clinical features and prognostic impact from a multicenter retrospective study

TL;DR

This study finds that anti-synthetase syndrome is linked to a higher risk of malignancy compared to other myositis types, with malignancy affecting survival rates.

Contribution

The study identifies anti-synthetase syndrome as an independent risk factor for malignancy in myositis patients, challenging previous assumptions about its low-risk profile.

Findings

ASyS patients had a 15.5% malignancy prevalence compared to 9.2% in non-ASyS patients.

ASyS was an independent risk factor for malignancy (adjusted OR 2.65).

Malignancy presence was associated with worse overall survival (P < 0.001).

Abstract

To delineate the clinical characteristics, identify risk factors (including the exploratory role of anti-Ro-52 antibody), and assess the prognostic implications of malignancy in patients with anti-synthetase syndrome (ASyS).

In this retrospective multicenter study, patients with idiopathic inflammatory myopathies (IIM) were analyzed, comprising 103 ASyS and 261 non-ASyS patients [including dermatomyositis (n = 195), immune-mediated necrotizing myopathy (n = 9), overlap myositis (n = 12), and other IIM subtypes (n = 45)]. Participants were stratified into four groups based on ASyS and malignancy status: ASyS with malignancy (ASyS-MAL), ASyS without malignancy, non-ASyS with malignancy (non-ASyS-MAL), and non-ASyS without malignancy. Data on demographics, clinical features, serology, and survival were collected. Multivariate logistic regression identified malignancy-associated factors, and Kaplan-Meier analysis compared survival.

Malignancy prevalence was 15.5% (16/103) in ASyS patients vs. 9.2% (24/261) in non-ASyS patients (P = 0.074). Multivariate analysis identified ASyS as an independent risk factor for malignancy (adjusted OR 2.65, 95% CI 1.15–6.11, P = 0.022), along with advancing age (adjusted OR 1.04 per year, 95% CI 1.01–1.07, P = 0.005). Comparative analysis showed ASyS-MAL patients had significantly higher creatine kinase (CK) levels (median 978 vs. 336 U/L, P = 0.018) and a 100% prevalence of myositis-specific antibodies (MSAs), while non-ASyS-MAL patients had a higher prevalence of heliotrope rash (75.0% vs. 37.5%, P = 0.019). The presence of malignancy was associated with worse overall survival (P < 0.001). ASyS-MAL patients had a median survival of 36.8 months, compared to 46.2 months in non-ASyS-MAL patients (log-rank P = 0.138).

Anti-synthetase syndrome is an independent risk factor for malignancy in patients with myositis, challenging the traditional view of ASyS as a low-risk subtype. Systematic malignancy screening is warranted for all ASyS patients, particularly those over 60 years of age. The role of anti-Ro-52 as an independent predictor was not confirmed and requires further study.

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