Rituximab in the Treatment of Jo1 Antibody-associated Antisynthetase Syndrome: Anti-Ro52 Positivity as a Marker for Severity and Treatment Response

J Rheumatol. 2016 Aug;43(8):1566-74. doi: 10.3899/jrheum.150844. Epub 2016 Jun 1.

Abstract

Objective: Rituximab (RTX) has been used successfully for the treatment of severe Jo1 antibody-associated antisynthetase syndrome. The aim of this retrospective study was to evaluate the effect of RTX in severe Jo1 antisynthetase syndrome and determine predictive factors for response.

Methods: There were 61 patients with Jo1 antisynthetase syndrome identified; 18 of these received RTX. One patient was lost to followup. The remaining 17 patients and 30 out of 43 patients who were treated with conventional immunosuppressive (IS) drugs were followed for a mean of 35 months and 84 months, respectively.

Results: Polymyositis/dermatomyositis (95%) and interstitial lung disease (ILD; 66%) were the dominant clinical manifestations. Detection of anti-Ro52 antibodies (43%) was significantly associated with acute-onset ILD (p = 0.016) with O2 dependency, and patients with high concentrations of anti-Ro52 (20%) had the highest risk (p = 0.0005). Sixteen out of 18 patients (89%) showed a fast and marked response to RTX. Among those patients who were highly positive for anti-Ro52, response to RTX was seen in 7 out of 7 cases (100%), but no response to cyclophosphamide (n = 4), cyclosporine A (n = 3), azathioprine (n = 9), methotrexate (n = 5), or leflunomide (n = 2) was observed. One patient treated with RTX died of pneumonia.

Conclusion: RTX is effective in the treatment of severe forms of Jo1 antisynthetase syndrome. In our retrospective study, the presence of high anti-Ro52 antibody concentrations predicts severe acute-onset ILD and nonresponse to IS drugs. In contrast to conventional IS, RTX is equally effective in patients with Jo1 antisynthetase syndrome, independent of their anti-Ro52 antibody status.

Keywords: ANTISYNTHETASE ANTIBODIES; INTERSTITIAL LUNG DISEASE; Jo1; POLYMYOSITIS; Ro52.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / analysis*
  • Dermatomyositis / drug therapy*
  • Dermatomyositis / immunology
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / immunology
  • Male
  • Middle Aged
  • Myositis / drug therapy*
  • Myositis / immunology
  • Retrospective Studies
  • Ribonucleoproteins / immunology*
  • Rituximab / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Autoantibodies
  • Immunosuppressive Agents
  • Ribonucleoproteins
  • SS-A antigen
  • Rituximab

Supplementary concepts

  • Antisynthetase syndrome