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

Respir Med. 2020 Oct:172:105983. doi: 10.1016/j.rmed.2020.105983. Epub 2020 May 16.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Interstitial lung disease; Melanoma differentiation-associated gene 5; Ultra-low dose rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies*
  • Cyclophosphamide / administration & dosage
  • Cytomegalovirus Infections / complications
  • Dermatomyositis / complications
  • Dermatomyositis / drug therapy*
  • Dermatomyositis / immunology*
  • Dermatomyositis / mortality
  • Female
  • Humans
  • Interferon-Induced Helicase, IFIH1 / immunology*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / immunology*
  • Lung Diseases, Interstitial / mortality
  • Male
  • Middle Aged
  • Opportunistic Infections / complications
  • Polymyositis / complications
  • Polymyositis / drug therapy*
  • Polymyositis / immunology*
  • Polymyositis / mortality
  • Retrospective Studies
  • Rituximab / administration & dosage*
  • Time Factors
  • Treatment Outcome

Substances

  • Autoantibodies
  • Rituximab
  • Cyclophosphamide
  • IFIH1 protein, human
  • Interferon-Induced Helicase, IFIH1