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Introduction Evaluating long-term outcomes in limited cutaneous systemic sclerosis (lcSSc) is challenging due to later and less frequent organ involvement compared to diffuse cutaneous systemic sclerosis (dcSSc). We test a novel composite ‘time to clinically meaningful progression’ endpoint (MINIMISE) in a large SSc cohort to evaluate its potential role as a future clinical trial endpoint. We explore differences in outcomes between those with anti-centromere antibody (ACA+) and those without (ACA-) hypothesising that ACA- patients show greater rates of disease progression which could be especially informative in clinical trials.Material and Methods Demographic, clinical, and serological data were collected from 2894 SSc patients in our centre. We performed a time to event analysis for the MINIMISE composite outcome from disease onset, defined as first non-Raynaud’s SSc manifestation. Outcomes included: pulmonary arterial hypertension (PAH) (haemodynamic definition at time of diagnosis on right heart catheter), interstitial lung disease (ILD) with forced vital capacity (FVC) <70% predicted or worsening of established ILD (reduction in FVC >10% in 12 months or FVC reduction 5-9% with concomitant DLCO reduction >15%), severe cardiac involvement (left ventricular ejection fraction <45% or pericardial effusion impairing cardiac function or arrhythmia requiring antiarrhythmic therapy), severe gastrointestinal (GI) involvement (enteral nutrition supplementation >3 weeks or parenteral feeding or hospitalisation for intestinal pseudo-obstruction), scleroderma renal crisis, severe digital vasculopathy requiring hospitalisation, absolute increase >5 modified Rodnan skin score or all-cause mortality.Kaplan Meier survival failure estimates curves and Cox proportional hazard regression analysis compared across disease and ACA subsets. P<0.05 significant.Results Table 1 summarises baseline cohort characteristics. Around one third had dcSSc which associated with more frequent disease complications except for PAH and severe GI involvement that were more frequent in lcSSc. 902 (31.6%) patients met the outcome in the first 10 years of disease; 543 in lcSSc group. Survival analysis revealed significantly higher frequency of MINIMISE events in dcSSc vs lcSSc, hazard ratio (HR) (4.93; 95% CI: 4.09-5.93, p<0.001) (figure 1). In lcSSc, ACA+ patients had significantly fewer MNIMISE events than ACA- (HR 0.49; 95% CI:0.36-0.67, p<0.001) (figure 2).Conclusions In lcSSc, clinically meaningful progression, defined by MINIMISE endpoint, is more frequent in ACA-negative patients. This subgroup may have greatest need and benefit from disease-modifying treatment earlier. This could be explored in a long-term event driven study with our data suggesting a large cohort and long term follow up will be essential to show benefit.Abstract OC.37 Figure 1Time to MINIMISE event for lcSSc and dcSScAbstract OC.37 Figure 2Time to MINIMISE event for ACA+ and ACA- IcSScAbstract OC.37 Table 1Baseline cohort characteristics