Clinical manifestations and long-term outcome of anti-Jo1 antisynthetase patients in a large cohort of Spanish patients from the GEAS-IIM group

Abstract

Objective

To evaluate the clinical manifestations, long-term clinical outcome and longitudinal pulmonary function in a large cohort of Spanish patients with anti-Jo1 antibodies.

Methods

We retrospectively analyzed the clinical data and lung function parameters of 148 anti-Jo1 patients recruited from a multicentre registry including 18 Spanish hospitals. A composite endpoint was defined, comprising death due to respiratory failure directly related to antisynthetase syndrome (ASS), the need for long-term oxygen therapy or lung transplantation.

Results

Median follow-up was 78.3 months. Clinical presentation patterns at onset are as follows: isolated interstitial lung disease (ILD) (32.4%), isolated myositis (26.9%), concomitant myositis and ILD (22.8%), and isolated polyarthritis (17.9%). Myositis with ILD was the most frequent final clinical phenotype (67.6%). In most ASS patients, ILD was a non-progressive disease, tending to stabilize with therapy. The endpoint was reached in a significantly larger number of ILD patients with dyspnea at onset than those with paucisymptomatic or asymptomatic forms (p = 0.01). A steady FVC decrease was the hallmark of patients with end-stage lung disease. Estimated survival rates were 87.7% and 75.4% at 5 and 10 years, respectively. Cancer (p = 0.02) and advanced age at ASS diagnosis (p < 0.0001) were related to poorer survival. Mortality was significantly higher than in the general Spanish population, with a standardised mortality ratio (95% CI) of 4.03 (2.79–5.64).

Conclusions

Anti-Jo1 ASS is a heterogeneous syndrome. ILD in ASS under immunosuppressive therapy is mainly a non-progressive disease. Dyspnea at ILD onset and a steady FVC decrease over time were related to a poorer respiratory prognosis.

Introduction

Antisynthetase syndrome (ASS) is a heterogeneous clinical condition that was first described in the setting of idiopathic inflammatory myopathies (IIM) as a constellation of associated signs and symptoms including polymyositis (PM) or dermatomyositis (DM), interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon (RP), fissured hyperkeratosis on the lateral aspects of the fingers known as “mechanic’s hands”, and fever [1]. The hallmark of this syndrome is serum titers of one of several possible autoantibodies against aminoacyl-transfer RNA synthetases (anti-ARS Abs). Eight different anti-ARS Abs, almost always mutually exclusive [2], have been described to date, with anti-histidyl-tRNA synthetase (anti-Jo1) being the first and most common [3], [4], [5], [6].

Despite the efforts of recent publications, the clinical course and outcome of ASS patients is still incompletely defined, in particular the long-term, longitudinal effect on the lung. Studies exclusively focussing on ASS patients are scarce and usually include small cohorts [2], [7], [8], [9]. Up to now, only one recent international multicentre study in a large number of anti-Jo1 ASS patients has specifically analyzed the presentation pattern of the disease and its variations over time [10]. Similarly, there is little longitudinal data on the lung function changes occurring in ASS patients [11].

In an attempt to address some of these gaps, we conducted this multicentre study with the following aims: to assess the clinical spectrum at onset, the disease course, and the long-term outcome, including associated conditions, survival, and mortality rates in a large Spanish cohort of anti-Jo1 ASS patients, and to examine the longitudinal lung function changes occurring in ASS patients with ILD within this cohort.