A MATRIX PREDICTION MODEL FOR THE SIX-MONTH MORTALITY RISK IN PATIENTS WITH ANTI-MELANOMA DIFFERENTIATION-ASSOCIATED PROTEIN-5 POSITIVE DERMATOMYOSITIS

BackgroundRecently, the autoantibody recognizing melanoma differentiation-associated gene 5 (anti-MDA5) is of the greatest concern as a specific autoantibody of dermatomyositis (DM), since it delineates a unique clinical phenotype of DM with a high risk of life-threatening lung complications. Considering routine clinical characteristics at baseline are still desired candidates for screening potential mortality predictors, in order to as early as possible stratify the mortality risk in anti-MDA5 positive DM patients before making therapeutic strategies.ObjectivesTo investigate the baseline independent risk factors for predicting 6-month mortality of anti-MDA5-positive DM patients and develop a matrix prediction model formed by these risk factors.MethodsThis was a real-world prospective observational study. The hospitalized patients with DM were included if they fulfilled the criteria including: aged over 18 years old; diagnosed as having DM according to the criteria proposed by Bohan and Peter or the modified Sontheimer definitions; and positive anti-MDA5 which was determined by both line immunoassay testing and enzyme-linked immunosorbent testing. The primary outcome was all-cause 6-month mortality after enrolment. A matrix prediction model was built with the mortality risk probability.ResultsThere were 82 DM patients enrolled (mean age of onset 50±11 years and 63% female), with 40 (49%) showing positive anti-MDA5. Gottron sign/papules (OR: 5.135, 95%CI: 1.489~17.708), arthritis (OR: 5.184, 95%CI: 1.455~18.467), interstitial lung disease (ILD, OR: 7.034, 95%CI: 1.157~42.785), and higher level of C4 (OR: 1.010, 95%CI: 1.002~1.017) were independent associators with positive anti-MDA5 in DM patients. Anti-MDA5-positive DM patients had significant higher 6-month all-cause mortality than those with anti-MDA5-negative (30% vs. 0%). Among anti-MDA5-positive DM patients, compared to the survivors, non-survivors had significantly advanced age of onset (59±6 years vs. 46±9 years), higher rates of fever (75% vs. 18%), positive carcinoma embryonic antigen (CEA, 75% vs. 14%), higher level of ferritin (median 2858 ug/L vs. 619 ug/L, all p<0.05). Multivariate COX regression showed ferritin≥1250 μg/L (HR: 10.4, 95%CI: 1.8~59.9), fever (HR: 11.2, 95%CI: 2.5~49.9), and positive CEA (HR: 5.2, 95%CI: 1.0~25.7) were independent risk factors of 6-month mortality.According to the matrix prediction model, anti-MDA5-positive DM patients could be stratified into three subgroups based on various probabilities of predicted mortality: (i) High-risk: eight patients with two of the above three features (including fever, serum ferritin≥1250 μg/L, and positive CEA) had high predicted mortality probability with 64%~85% (three red grids in Figure 1A), and the actual mortality was 75% (n=6) with 60%, 100%, and 100% respectively in three red grids (Figure 1B). Five patients with all of three features had extremely high predicted mortality probability with 97% (95%CI: 70%~100%, the dark red grid of Figure 1A), and the actual mortality was 100% in Figure 1B; (ii) Moderate-risk: nine patients with one of the above three features had moderate predicted mortality probability with 11%~29% (three yellow grids in Figure 1A), and the actual mortality was 11% (n=1) with 0%, 0%, and 17% respectively in three yellow grids (Figure 1B); (iii) Low-risk: eighteen patients with none of the above three features had low predicted mortality probability with 2% (95%CI: 0.2%~20%, the green grid in Figure 1A), and the actual mortality was 0% in the green grid (Figure 1B).ConclusionBaseline characteristics of fever, positive CEA, and ferritin≥1250 μg/L are risk factors for 6-month all-cause mortality in anti-MDA5-positive DM patients. A novel matrix prediction model composed of these three clinical indicators is firstly proposed to provide a chance for exploration of individual treatment strategies in anti-MDA5-positive DM subgroups with various probabilities of mortality risk.Disclosure of InterestsNone declared