Development of Pulmonary Hypertension in Over One‐Third of Patients With Th/To Antibody–Positive Scleroderma in Long‐Term Follow‐Up

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 74; no. 9; pp. 1580 - 1587
• Main Authors: Suresh, Shashank, Charlton, Devon, Snell, Erin K., Laffoon, Maureen, Medsger, Thomas A., Zhu, Lei, Domsic, Robyn T.
• Format: Journal Article
• Language: English
• Published: Boston, USA Wiley Periodicals, Inc 01.09.2022; Wiley Subscription Services, Inc
• Subjects: Antibodies; Disease control; Health care facilities; Hypertension; Lung diseases; Muscles; Patients; Pulmonary hypertension; Scleroderma; Skin tests; Systemic sclerosis; Thickening
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.42152

Objective This study was undertaken to describe clinical manifestations in patients with Th/To antibody–positive systemic sclerosis (SSc) during long‐term follow‐up. Methods We performed a case–control study involving anti‐Th/To antibody–positive patients with SSc who were newly referred to the University of Pittsburgh Medical Center and the Pittsburgh Scleroderma Center from 1980 to 2015. For every case, 2 anti‐Th/To antibody–negative SSc patients (the first 2 consecutively seen after a case) were used as controls. Long‐term disease manifestations and survival were then compared between cases and controls. Results A total of 204 anti‐Th/To antibody–positive SSc patients and 408 controls were identified. The cohort had a mean ± SD age of 52 ± 12.9 years, and 76% of individuals were women. Anti‐Th/To antibody–positive patients more often presented without skin thickening (P < 0.0001) and had a higher rate of pulmonary hypertension (PH) (P < 0.0001) and interstitial lung disease (P = 0.05) compared to anti‐Th/To antibody–negative SSc controls. Anti‐Th/To antibody–positive SSc patients also had less frequent muscle and joint involvement than anti‐Th/To antibody–negative SSc controls (P < 0.0001). After a median clinical follow‐up period of 6.1 years (interquartile range 2.4–12.7), 38% of anti‐Th/To–positive patients had developed PH compared to 15% of anti‐Th/To antibody–negative SSc controls (P < 0.0001). The rate of PH classified as World Health Organization (WHO) Group 1 pulmonary arterial hypertension [PAH] was 23% in anti‐Th/To–positive patients compared to 9% in anti‐Th/To antibody–negative SSc controls (P < 0.0001). After adjusting for age and sex, anti‐Th/To antibody positivity was associated with a hazard ratio (HR) of 3.3 (95% confidence interval 2.3–4.9) for increased risk of developing PH at 10 years of follow‐up from the first scleroderma center visit. Conclusion This is the largest cohort of patients with anti‐Th/To antibody–positive SSc with long‐term follow‐up data. The very high rate (38%) and associated independent risk of anti‐Th/To antibody–positive patients developing PH in follow‐up, particularly in WHO Group 1 PAH patients, is striking. Patients presenting with limited skin involvement should be tested for Th/To antibodies, and if present, careful monitoring for PH is warranted.