AB0695 ANTI-TH/TO POSITIVITY IN SYSTEMIC SCLEROSIS: ANALYSIS OF PULMONARY INVOLVEMENT, ORGAN DAMAGE ACCRUAL AND MORTALITY IN AN ITALIAN MONOCENTRIC COHORT

Abstract

BackgroundAnti-Th/To antibodies, detected in 2-5% Systemic Sclerosis (SSc) patients, are associated to interstitial lung disease (ILD)1 in half of the cases. However, long-term data on ILD as well as on organ damage accrual are lacking.ObjectivesTo describe the clinical associations of anti-Th/To SSc patients, focusing on ILD, organ damage and mortality.MethodsMonocentric retrospective study. 1) Description of clinical associations of anti-Th/To SSc patients (2013 ACR/EULAR criteria). 2) Case-control study: anti-Th/To vs anti-Topoisomerase (anti-Topo)1 patients (1:3; matched for sex and age at SSc onset) regarding a) ILD b) organ damage c) survival. ILD progression was assessed through pulmonary function tests (PFTs) at baseline (T0) and after 1 (T1), 5 (T5), 10 (T10) and 20 (T20) years. Organ damage was evaluated with SCTD-Damage Index (SCTD-DI)2. Continuous data are expressed as median [IQR].ResultsWe identified 13 anti-Th/To patients (all Caucasians, F/M=10/3, median age at SSc onset: 50 [37-67] years). Anti-Th/To were assayed by RNA immunoprecipitation in 8/13 and by immunoblotting in 5/13 cases.1) 2/13 patients had SSc/myositis overlap syndrome: 1 associated to anti-SRP, 1 negative for myositis specific antibodies and affected by a synchronous (±3 years from onset) cancer. All presented lcSSc, 77% esophageal symptoms, 46% digital ulcers (DUs), 40% ILD, 39% telangiectasias, 39% heart involvement (3 pericarditis, 1 myocarditis in patient anti-SRP+, 1 arrhythmia), 15% gastrointestinal symptoms, 15% myositis and 8% calcinosis. No patients presented synovitis, joint contractures, pulmonary arterial hypertension nor scleroderma renal crisis.2a) Anti-Th/To ILD patients, as compared to 39 anti-Topo 1, less frequently required immunosuppression and never required antifibrotic or O2 therapy (Table 1); ILD progression (%pFVC decline ≥10% or %pFVC decline 5-10% and %pDLCO decline ≥15%) was shown for 3/13, albeit, after a longer interval than in 8/39 anti-Topo 1 progressors (15 [10-15] vs 1 [1-6.3] years, p:0.05); none died because of ILD.Table 1.anti-Th/To+ n=13anti-Topo 1+ n=39p-valueILD on HRTC4/10 (40)28/33 (85)0.01Immunosuppressants1/13 (8)16/39 (41)0.04Antifibrotic and/or O20/13 (0)8/39 (21)0.18PH secondary to ILD0/13 (0)6/39 (15)0.32SSc-ILD related death0/13 (0)6/39 (15)0.32%pFVC T0105 [85-114]90 [81-114]0.26%pFVC T1107 [97-112]88 [80-108]0.09%pFVC T597 [84-114]99 [83-111]0.88%pFVC T10103 [91-114]88 [80-112]0.23%pFVC T20104 [83-111]81 [74-103]0.35%pFVC <70% T00/13 (0)3/39 (8)0.56%pFVC <70% T10/12 (0)3/39 (8)1.00%pFVC <70% T50/10 (0)3/33 (9)1.00%pFVC <70% T100/7 (0)3/25 (12)1.00%pFVC <70% T200/5 (0)1/8 (13)1.00Progressive fibrosis (PF)* [T1-T0]0/12 (0)5/39 (13)0.32PF* [T5-T0]1/10 (10)5/33 (15)1.00PF* [T10-T0]1/7 (14)4/25 (16)1.00PF* [T20-T0]2/5 (40)0/8 (0)0.20Continuous data are presented as median [IQR] and compared with Mann-Whitney test; categorical data are presented as number/number available data (%) and compared with Chi-square test/Fisher’s exact test. *Progressive fibrosis= %pFVC decline ≥10% or 5-10% %pFVC decline and %pDLCO decline ≥15%.2b) During 16 [6-20] years of follow-up, SCTD-DI score progressively increased, but remained low in all patients (SCTD-DI ≤5) and was significantly lower than in anti-Topo 1 (Figure 1a), mainly due to ILD, joint contractures and DUs in the latter group (85% vs 40%, p:0.01; 39% vs 0%, p:0.01; 77% vs 46%, p:0.08).Figure 1.2c) 4/13 patients died at 81 [75-86] years after 10 [8-13] years of disease duration, none due to SSc. The survival curves of the two groups are showed in Figure 1b.ConclusionIn this cohort anti-Th/To patients showed a mild SSc phenotype, characterized by lower organ damage, more favorable long-term ILD functional outcome (although detectable in 40% of patients) and higher survival, as compared to matched anti-Topo 1 patients. Larger multicenter studies are needed to confirm these data.