A Matrix Prediction Model for the 6-Month Mortality Risk in Patients With Anti-Melanoma Differentiation-Associated Protein-5-Positive Dermatomyositis

Zhi-Ming Ouyang; Jian-Zi Lin; Ao-Juan Tang; Ze-Hong Yang; Li-Juan Yang; Xiu-Ning Wei; Qian-Hua Li; Jin-Jian Liang; Dong-Hui Zheng; Bing-Peng Guo; Gui Zhao; Qian Han; Lie Dai; Ying-Qian Mo

doi:10.3389/fmed.2022.860798

A Matrix Prediction Model for the 6-Month Mortality Risk in Patients With Anti-Melanoma Differentiation-Associated Protein-5-Positive Dermatomyositis

Front Med (Lausanne). 2022 Apr 1:9:860798. doi: 10.3389/fmed.2022.860798. eCollection 2022.

Authors

Zhi-Ming Ouyang¹, Jian-Zi Lin¹, Ao-Juan Tang², Ze-Hong Yang³, Li-Juan Yang¹, Xiu-Ning Wei¹, Qian-Hua Li¹, Jin-Jian Liang¹, Dong-Hui Zheng¹, Bing-Peng Guo⁴, Gui Zhao⁴, Qian Han⁴, Lie Dai¹, Ying-Qian Mo^{1

2}

Affiliations

¹ Department of Rheumatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Rheumatology, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, China.
³ Departments of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

Objectives: The purpose of this study was to investigate the baseline independent risk factors for predicting 6-month mortality of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis (DM) and develop a matrix prediction model formed by these risk factors.

Methods: The hospitalized patients with DM who completed at least 6-month follow-up were recruited as a derivation cohort. The primary exposure was defined as positive anti-MDA5 at the baseline. The primary outcome was all-cause 6-month mortality after enrollment. A matrix prediction model was developed in the derivation cohort, and another published cohort was used for external validation.

Results: In derivation cohort, 82 patients with DM were enrolled (mean age of onset 50 ± 11 years and 63% women), 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 (OR: 7.034, 95%CI: 1.157-42.785), and higher level of C4 (OR: 1.010, 95%CI: 1.002-1.017) were the independent associators with positive anti-MDA5 in patients with DM. Patients with anti-MDA5-positive DM had significant higher 6-month all-cause mortality than those with anti-MDA5-negative (30 vs. 0%). Among the patients with anti-MDA5-positive DM, 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 2,858 ug/L vs. 619 ug/L, all p < 0.05). A stepwise multivariate Cox regression showed that ferritin ≥1,250 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 the independent risk factors of 6-month mortality. A matrix prediction model was built to stratify patients with anti-MDA5-positive DM into different subgroups with various probabilities of 6-month mortality risk. In an external validation cohort, the observed 6-month all-cause mortality was 78% in high-risk group, 43% in moderate-risk group, and 25% in low-risk group, which shows good accuracy of the model.

Conclusion: Baseline characteristics such as fever, ferritin ≥1,250 μg/L, and positive CEA are the independent risk factors for 6-month all-cause mortality in patients with anti-MDA5-positive DM. A novel matrix prediction model composed of these three clinical indicators is first proposed to provide a chance for the exploration of individual treatment strategies in anti-MDA5-positive DM subgroups with various probabilities of mortality risk.

Keywords: anti-melanoma differentiation-associated protein-5; carcinoma embryonic antigen; dermatomyositis; fever; matrix prediction model; mortality; serum ferritin.