Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD

• Published in: Respiratory medicine 2020-10, Vol.172, p.105983-105983, Article 105983
• Main Authors: Mao, Meng-meng, Xia, Shu, Guo, Bing-peng, Qian, Wei-ping, Zheng, Ze-xuan, Peng, Xiao-min, Chen, Rong-chang, Luo, Qun, Han, Qian
• Format: Article
• Language: English
• Subjects: Algorithms; Antibodies; Blood tests; CD4 antigen; Cyclophosphamide; Cytokines; Cytomegalovirus; Depletion; Dermatomyositis; Evaluation; Health services; Immunotherapy; Interleukin 10; Interstitial lung disease; Lung diseases; Medical prognosis; Melanoma; Melanoma differentiation-associated gene 5; Monoclonal antibodies; Mortality; Opportunist infection; Patients; Plasma; Polymyositis; Regression analysis; Risk analysis; Risk factors; Rituximab; Targeted cancer therapy; Ultra-low dose rituximab; Variance analysis
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2020.105983

To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment. •Anti-MDA5 positive interstitial lung disease is characterized by rapid progression and high mortality.•We showed the first evidence on use of ultra-low dose of rituximab in anti-MDA5 positive ILD.•RTX add-on may lead to a trend of decreased mortality compared with conventional treatment.•Infection was major adverse effect of RTX even though with lower dose administered.