Background/Purpose: To evaluate clinical associations of anti-Th/To antibodies in SSc patients in a multicentre international cohort, focusing on interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), synchronous malignancies, organ damage, mortality.

Methods: A case-control study of prospectively collected data from 23 EUSTAR centres was performed (CP144). For every anti-Th/To+ SSc case, centres provided 2 anti-Th/To- SSc controls matched by sex, age at onset (±5 years) and disease duration (±24 months). ILD functional progression was defined as absolute decline in %pFVC≥5% and/or %pDLCO >10% over 12 months¹. Synchronous malignancies were defined as diagnosed within ±2 years from SSc onset². Organ damage was evaluated through the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI)³.

Results: 89 anti-Th/To+ SSc patients, as compared to 178 anti-Th/To- (Table 1), had higher rate of concomitant anti-Ro52 positivity and lower frequency of diffuse cutaneous involvement and digital ulcers/pitting.

ILD was detected in 40.5% anti-Th/To+ patients (vs 55.2% in anti-Th/To-, p:0.032), with non-specific interstitial pneumonia (NSIP) pattern in 71.9%. Functional progression was detected in 46.9% during the first 5 years of disease, similarly to the control group. Only 1 (3.1%) anti-Th/To+ patient developed group 3 PH. A higher prevalence of usual interstitial pneumonia (UIP) pattern was found in cases.

PAH was confirmed at right heart catheterization in 3 (3.6%) anti-Th/To+ cases, slightly less frequently than in controls.

Malignancies rate was similar in the two groups. In anti-Th/To+ cases, the most common synchronous cancer type was breast cancer in 5 cases (2 infiltrating ductal carcinomas, 1 infiltrating lobular carcinoma, 2 not specified), followed by 1 pancreatic, 1 thyroid 1 cecum cancer.

Anti-Th/To+ patients accrued less organ damage as compared to controls, exhibiting lower DI scores after 2, 3 and 5 years from SSc onset.

6 (6.7%) anti-Th/To+ patients died at 79.5 (72.5-84.3) years of age and 9.5 (9.0-17.5) years of disease duration with no deaths attributable to SSc-ILD or other SSc complications. Survival curves are depicted in Figure 1: anti-Th/To+ patients had a survival rate of 100.0% at 1 year, 98.8% at 5 years, and 89.9% at both 10 and 15 years of disease duration, slightly higher than controls (98.8% at 1, 94.5% at 5, 90.3% at 10 and 76.7% at 15 years of disease duration).

Conclusion: Through the analysis of this multicentric series of anti-Th/To+ SSc patients, well known clinical associations were confirmed in particular limited cutaneous involvement in most cases and ILD in half of the cases. PAH seems to be part of anti-Th/To spectrum only in a small percentage of patients while the relationship with synchronous malignancies needs to be better explained in future analyses. Globally, it seems that anti-Th/To+ patients have favorable outcome characterized by mild organ damage and good survival.

References: ¹Raghu G. 2022;²Lazzaroni MG. 2017;³Ferdowsi N. 2019

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-clinical-phenotype-of-anti-th-to-patients-in-systemic-sclerosis-a-case-control-study-within-the-european-scleroderma-trials-and-research-eustar-cohort/