POS0876 SERUM INTERFERON SCORE PREDICTS SEVERITY OF PATIENT REPORTED HAND DISABILITY IN SYSTEMIC SCLEROSIS

Abstract

BackgroundHand involvement is a major cause of disability in systemic sclerosis (SSc) patients. Loss of hand function is the result of a complex and overlapping series of manifestations including Raynaud’s, cutaneous ulcerations as well as skin fibrosis, joint inflammation, and contractures. The natural history of hand involvement in SSc and potential biomarkers to predict its outcome are still poorly defined. Type 1 Interferon (IFN) activation has been extensively correlated with skin fibrosis, joint disease activity, vascular manifestations, and poor prognosis in SSc patients.ObjectivesTo characterize hand disability burden in SSc and explore its relationship with IFN activation in a national, multicenter, longitudinal, observational cohort of patients with SSc.MethodsThe Cochin Hand Function Scale (CHFS) was assessed in consecutively enrolled SSc patients at baseline and after 12 months. CHFS values above the patient acceptable symptom state (PASS)(CHFS>25)1 were considered as clinically meaningful hand impairment (CMHI). Minimal clinically important difference (MCID) in CHFS for improvement (reduction of 13.1%) and worsening (increase >24.6%) were assessed in longitudinal analysis. Serum IFN score was evaluated as previously described2.ResultsA total of 397 SSc patients from 10 centers (female 85.3%, aged 54.9±11.5 years, white Caucasian 88.2%) were available for longitudinal (12m) analysis. The median disease duration was 9 (IQR 3-16) years, 37.1% of patients had a diffuse cutaneous variant, while anticentromere (ACA) and anti-Scl70 antibody positivity was reported in 41.2% and 33.5% of cases, respectively. Hand digital ulcers, forearm-hand-finger skin score ≥6, and tenosynovitis/arthritis were clinically reported in 24.0%, 15.3%, and 17.9% of patients, respectively. 37.3% of patients reported a CHFS > PASS at baseline. CMHI was associated with male gender (p<.001), diffuse cutaneous variant (p<.001), anti Scl70 positivity (p<.001), ACA negativity (p=.002), and digital ulcers (p=.001). Patients with CMHI had greater serum IFN score than patients with CHFS < PASS (p=.002). In multivariate logistic regression analysis, high serum IFN score remained associated with CHFS>PASS when adjusted for male gender, ACA positivity, anti-Scl70 positive, diffuse subset, and current digital ulcers (OR 2.67, p=.005). Over the 12-month follow-up, vasoactive and immunosuppressive treatment were escalated or introduced in 7.2 and 7.8% of patients, respectively. Median CHFS worsened over time (from 18 (IQR 5-37) to 21 (IQR 6-37), p=.002)) with 32.5% of patients having a clinically meaningful worsening and 32.0% improving their hand function. Functional hand worsening was associated with lower baseline CHFS (p=.001) and ACA negativity (p=.002), while improving with female gender (p=.047), limited cutaneous subset (p=.029), higher baseline CHFS (p=.001), and active baseline tenosynovitis (p=.014).ConclusionOne third of the patients within our cohort complain of a significant hand impairment. This is associated with higher IFN activation and worsens at group level in patients despite standard of care treatment.