Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients' leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients. Methods: Patients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model. Results: There are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts. Conclusions: The CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

Adalimumab exhibits superiority over etanercept in terms of a numerically higher response rate and equivalent adverse events: A real-world finding.

INTRODUCTION: Adalimumab (ADA) and etanercept (ETN) are the most commonly applied biologics for rheumatoid arthritis (RA) management in China; however, the evidence regarding their superiority is controversial. In addition, in real-world clinical settings, many factors may affect the application of these agents, such as dosage and administration period. Therefore, the present real-world study aimed to compare the efficacy and safety of ADA and ETN treatment in RA patients via the propensity score matching method. METHODS: In total, 105 RA patients receiving ADA (n = 66) or ETN (n = 39) were reviewed in this retrospective study. The propensity score matching method was used to eliminate discrepancies in baseline features. Clinical response, low disease activity (LDA), and remission were evaluated based on the DAS28. RESULTS: Before propensity score matching, compared with ETN, ADA yielded higher rates of clinical response at W24 (97.0% vs. 84.6%, p = .021), LDA at W12 (78.8% vs. 51.3%, p = .003), and remission at W24 (75.8% vs. 46.2%, p = .002). After propensity score matching, compared with ETN, ADA only achieved a higher rate of clinical response at W24 (96.3% vs. 77.8%, p = .043), whereas the rates of LDA and remission were not different between ADA and ETN treatments at any time point (all p > .05). In addition, the incidence of adverse events was not significantly different between the ADA and ETN treatments (all p > .05). CONCLUSION: ADA shows superiority over ETN in terms of a numerically greater response rate and equivalent adverse events.

Serum 14­3­3η levels are increased and associated with a higher risk of osteoporosis in patients with rheumatoid arthritis: A meta­analysis.

14-3-3η can regulate the cell cycle, immunity, inflammation and the secretion of matrix metalloproteinases, while it may also be involved in the development of rheumatoid arthritis (RA) and promote bone injury. Therefore, the present meta-analysis focused on the dysregulated serum levels of 14-3-3η and its association with osteoporosis in patients with RA. Studies comparing the serum levels of 14-3-3η between patients with RA and healthy controls (HCs) or patients with RA with different bone mineral densities were retrieved from the EMBASE, Web of Science, PubMed and Cochrane databases. A total of 14 studies comprising 2,164 patients with RA and 1,136 HCs were included and analysed. Pooled analyses showed that the serum levels of 14-3-3η were enhanced in patients with RA compared with HCs [standardized mean difference (SMD): 1.34; 95% confidence interval (CI): 1.01-1.66; P<0.001]. In addition, the serum levels of 14-3-3η were also significantly higher in patients with RA with osteoporosis and osteopenia compared with those with normal bone mass (SMD: 1.96; 95% CI: 0.01-3.92; P=0.049 and SMD: 0.80; 95% CI: 0.09-1.52; P=0.028, respectively). Begg's and Egger's tests demonstrated that the publication bias for each evaluated indicator was low (all P>0.05). However, sensitivity analyses revealed that the findings were not very robust, which may be due to the omission of several individual studies. Overall, the present meta-analysis suggested that the serum levels of 14-3-3η were elevated and were associated with a higher risk of osteoporosis in patients with RA, thus supporting its potency as a circulating biomarker in the management of RA.

Gender differences in patients with anti-MDA5-positive dermatomyositis: a cohort study of 251 cases.

OBJECTIVE: To investigate the impact of sex differences on the clinical characteristics and prognosis of patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM). METHODS: We retrospectively analyzed a cohort of 251 patients with MDA5+ DM, including 71 in the male group and 180 in the female group. A multivariate logistic regression model was built to analyze independent risk factors for RPILD in each group. An ROC curve was drawn to evaluate the predictive value of independent risk factors. Kaplan‒Meier analysis was used to compare the cumulative survival rates, while the log-rank test was used to test for significant differences between the two groups. RESULTS: Patients in the male group had a significantly higher prevalence of heliotrope rash, V sign, severe interstitial lung disease (ILD), and rapidly progressive interstitial lung disease (RPILD) than those in the female group. Anti-Ro52 positivity, high CRP level and short disease were identified as independent risk factors for RPILD in both male and female groups by multivariate logistic regression analysis. The mortality rates of males and females were 33.8% and 22.0%, respectively, and the survival time of patients in the male group was shorter than that in the female group. CONCLUSION: Male patients with MDA5+ DM exhibit an increased risk of RPILD, elevated mortality rates and reduced overall survival time compared to their female counterparts, and anti-Ro52 positivity may be an unfavorable prognostic factor for these patients. Key Points • The prevalence of solar rash, V sign, severe interstitial lung disease (ILD) and rapidly progressive interstitial lung disease (RPILD) in anti-MDA5-positive female patients was significantly lower than that in male patients. • Positive Anti-Ro52, high CRP level, and short course of disease were independent risk factors for RPILD in both men and women. • Female patients exhibited a lower mortality rate than male patients (22.0% vs 33.8%) and demonstrated longer survival time.

Anxiety and depression in rheumatoid arthritis patients: prevalence, risk factors and consistency between the Hospital Anxiety and Depression Scale and Zung's Self-rating Anxiety Scale/Depression Scale.

Objectives: The aim was to explore the prevalence and independent risk factors for anxiety and depression in RA patients and to assess the consistency between the hospital anxiety and depression scale (HADS) and Zung's self-rating anxiety scale/depression scale (SAS/SDS). Methods: In total, 160 RA patients and 60 healthy controls (HCs) were enrolled consecutively, and HADS and SAS/SDS were completed. Results: The HADS-defined anxiety rate, HADS-defined depression rate, SAS-defined anxiety rate and SDS-defined depression rate were 36.9, 36.3, 29.4 and 29.4%, respectively, in RA patients, all of which were much higher in RA patients than in HCs (all P < 0.001). A relatively high consistency was observed between HADS-defined anxiety and SAS-defined anxiety (κ = 0.551, P < 0.001) and between HADS-defined depression and SDS-defined depression (κ = 0.563, P < 0.001) in RA patients. Interestingly, screened by multivariate logistic regression analyses, single/divorced/widowed marital status, swollen joint count, disease duration, ESR, physician's global assessment (PhGA) and DAS28 were independently correlated with HADS-defined or SAS-defined anxiety risk in RA patients; meanwhile, female biological sex, single/divorced/widowed marital status, rural location, disease duration, PhGA and DAS28 were independently associated with HADS-defined or SDS-defined depression risk in RA patients. Conclusion: Anxiety and depression are highly prevalent in RA patients and are independently correlated with single/divorced/widowed marital status and higher disease activity. In addition, the HADS presents a high consistency with the SAS/SDS with many fewer questions, which might be more suitable for long-term assessment of RA.

Identification of Three Different Phenotypes in Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis Patients: Implications for Prediction of Rapidly Progressive Interstitial Lung Disease.

OBJECTIVE: There is substantial heterogeneity among the phenotypes of patients with anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis (DM), hindering disease assessment and management. This study aimed to identify distinct phenotype groups in patients with anti-MDA5+ DM and to determine the utility of these phenotypes in predicting patient outcomes. METHODS: A total of 265 patients with anti-MDA5+ DM were retrospectively enrolled in the study. An unsupervised hierarchical cluster analysis was performed to characterize the different phenotypes. RESULTS: Patients were stratified into 3 clusters characterized by markedly different features and outcomes. Cluster 1 (n = 108 patients) was characterized by mild risk of rapidly progressive interstitial lung disease (RPILD), with the cumulative incidence of non-RPILD being 85.2%. Cluster 2 (n = 72 patients) was characterized by moderate risk of RPILD, with the cumulative incidence of non-RPILPD being 73.6%. Patients in cluster 3 (n = 85 patients), which was characterized by a high risk of RPILD and a cumulative non-RPILD incidence of 32.9%, were more likely than patients in the other 2 subgroups to have anti-Ro 52 antibodies in conjunction with high titers of anti-MDA5 antibodies. All-cause mortality rates of 60%, 9.7%, and 3.7% were determined for clusters 3, 2, and 1, respectively (P < 0.0001). Decision tree analysis led to the development of a simple algorithm for anti-MDA5+ DM patient classification that included the following 8 variables: age >50 years, disease course of <3 months, myasthenia (proximal muscle weakness), arthritis, C-reactive protein level, creatine kinase level, anti-Ro 52 antibody titer, and anti-MDA5 antibody titer. This algorithm placed patients in the appropriate cluster with 78.5% accuracy in the development cohort and 70.0% accuracy in the external validation cohort. CONCLUSION: Cluster analysis identified 3 distinct clinical patterns and outcomes in our large cohort of anti-MDA5+ DM patients. Classification of DM patients into phenotype subgroups with prognostic values may help physicians improve the efficacy of clinical decision-making.

Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody-Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk.

OBJECTIVE: Interstitial lung disease (ILD) is a common extramuscular complication contributing to significant morbidity and mortality in patients with dermatomyositis (DM) who are positive for antimelanoma differentiation-associated gene 5 antibody (anti-MDA5+). We conducted this study to investigate the association of anti-Ro52 antibodies with clinical characteristics and prognosis in patients with anti-MDA5+ DM. METHODS: We assessed a cohort of 246 patients with anti-MDA5+ DM. To calculate hazard ratios and 95% CIs for rapidly progressive ILD (RP-ILD) and death while controlling for potential confounders, variables selected by univariate Cox regression analysis were included in a multivariate Cox regression model with the stepwise forward-selection method. A 2-tailed analysis with P < 0.05 was considered to be statistically significant. RESULTS: A total of 246 patients with anti-MDA5+ DM were enrolled; 70 patients were male, and the patient group had an average age of 53.1 (12.4) years. Anti-Ro52 was present in 64.2% (158/246) patients. Patients with anti-MDA5+ DM who were positive for anti-Ro52 had a higher rate of RP-ILD (log-rank P < 0.001) and a higher mortality rate (log-rank P = 0.01). For patients with anti-MDA5+ DM who were positive for anti-Ro52, those with a short disease course and high inflammation were at increased risk of RP-ILD and death. The appearance of active rash was an independent protective factor of death. CONCLUSION: Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5+ DM, and their coexistence correlated with a higher rate of RP-ILD and mortality. Patients with a short disease course, with increased inflammation, and without rash were more likely to have a poor prognosis.

Time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients: a cohort study of 272 cases in China.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 positive (anti-MDA5+) DM has a close relationship with rapidly progressive interstitial lung disease (RPILD) and is associated with high mortality. However, data regarding the time-dependent risk of RPILD and deaths during disease progression are limited. We conducted this study to investigate whether the risk of RPILD and death were time-dependent or not in anti-MDA5+ DM. METHODS: We assessed a cohort of 272 patients with anti-MDA5+ DM. The clinical characteristics of patients with anti-MDA5+ were collected, and COX regression was used to analyse independent risk factors for RPILD and death. We also described changes in risk of RPILD and death over time and their potential clinical implications. RESULTS: There were 272 anti-MDA5+ DM patients enrolled in this study. According to the multivariate cox regression analysis, short disease course, high CRP level, anti-Ro52 positive and anti-MDA5 titre (++∼+++) were independent risk factors of RPILD. High creatine kinase level, high CRP level and RPILD were independent risk factors for death, and >90% RPILD and 84% mortality occurred in the first 6 months after disease onset. Notably, the first 3 months is a particularly high-risk period, with 50% of RPILD and 46% of deaths occurring. Hazards regarding RPILD and mortality diminished over time during a median follow-up of 12 months. CONCLUSION: These results suggest significant, time-dependent changes in RPILD and mortality risk in anti-MDA5+ DM patients, providing a cut-off time window to estimate disease progression and poor prognosis.

Systemic inflammation response index (SIRI) as a novel biomarker in patients with rheumatoid arthritis: a multi-center retrospective study.

OBJECTIVES: To evaluate the potential ability of systemic inflammation response index (SIRI) as a novel biomarker in patients with rheumatoid arthritis (RA) and explore the mechanisms. METHOD: Patients fulfilling the 2010 ACR/EULAR classification criteria for RA were enrolled in this study. Demographic, clinical, and laboratory characteristics of all subjects were collected. Neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), and SIRI were calculated. Statistical analysis was performed, and P-values < 0.05 were considered statistically significant. RESULTS: One thousand four hundred ninety-nine RA patients from five hospitals were included, with 366 healthy volunteers served as controls. The NLR, MLR, PLR, and SIRI significantly increased in RA patients. Receiver operating characteristics (ROC) curve analysis showed SIRI, and NLR could distinguish RA from healthy controls. Correlation analysis and multiple linear regression analysis indicated that SIRI and PLR positively correlated with disease activity in RA. The NLR, MLR, and SIRI increased significantly in patients with RA-associated interstitial lung disease (ILD). There was a good accuracy of SIRI in differentiating RA-ILD from RA patients without ILD. SIRI was also found to be higher in RA patients with tumor and could differentiate them from RA patients without tumor. CONCLUSIONS: SIRI could be evaluated as a novel, non-invasive, and suitable biomarker for assisting in the diagnosis process and demonstrating the disease activity of RA, as well as predicting RA-ILD and tumor development of RA patients. Key Points • As a novel biomarker, systemic inflammation response index (SIRI) may assist in the diagnosis process and indicate the disease activity of RA patients • SIRI may predict the development of RA-associated interstitial lung disease (RA-ILD) and tumor in RA patients • SIRI is more satisfactory than other blood cells-based indexes in the assessment of RA patients.