title: Efficacy of Rituximab in Refractory Inflammatory Myopathies Associated with Anti- Synthetase Auto-Antibodies: An Open-Label, Phase II Trial.
abstract: OBJECTIVE
  Anti-synthetase syndrome (anti-SS) is frequently associated with myositis and interstitial lung disease (ILD). We evaluated prospectively, in a multicenter, open-label, phase II study, the efficacy of rituximab on muscle and lung outcomes.
  
  
  METHODS
  Patients were enrolled if they were refractory to conventional treatments (prednisone and at least 2 immunosuppressants). They received 1 g of rituximab at D0, D15, and M6. The primary endpoint was muscular improvement based on manual muscular testing (MMT10, Kendall score in 10 muscles) at M12. Secondary endpoints were normalization of creatine kinase (CK) level, ILD improvement based on forced vital capacity and/or diffuse capacity for carbon monoxide, and number and/or doses of associated immunosuppressants.
  
  
  RESULTS
  Twelve patients were enrolled, and 10 completed the study. Only 2 patients presented an improvement of at least 4 points on at least two muscle groups (primary end-point). Overall, seven patients had an increase of at least 4 points on MMT10. CK level decreased from 399 IU/L (range, 48-11,718) to 74.5 IU/L (range, 40-47,857). Corticosteroid doses decreased from 52.5 mg/d (range, 10-70) to 9 mg/d (range, 7-65) and six patients had a decrease in the burden of their associated immunosuppressants. At baseline, all 10 patients presented with ILD. At M12, improvement of ILD was observed in 5 out of the 10 patients, stabilization in 4, and worsening in 1.
  
  
  CONCLUSIONS
  This pilot study of rituximab treatment in patients with refractory anti-SS provided data on evolution of muscular and pulmonary parameters. Rituximab should now be evaluated in a larger, controlled study for this homogenous group of patients.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00774462.
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allenbach
authors.affiliation: Département de Biostatistique, UMRS 943, UPMC, INSERM, Paris, France.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Guiguet
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Rigolet
authors.affiliation: Département de Médecine Interne, Hôpital Charles Nicole, Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marie
authors.affiliation: Centre de Référence pour les maladies auto-immunes systémiques rares (Sclérodermie) Hôpital Claude Huriez, Université Lille 2, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Département d'Immunologie, U905, Université Rouen Normandie, INSERM, Hôpital Universitaire de Rouen, Rouen, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Drouot
authors.affiliation: Département d'Immunologie, U905, Université Rouen Normandie, INSERM, Hôpital Universitaire de Rouen, Rouen, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Jouen
authors.affiliation: Département d'Immunologie, U905, Université Rouen Normandie, INSERM, Hôpital Universitaire de Rouen, Rouen, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Jacquot
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Kuberaka
authors.initials: K
authors.lastname: Mariampillai
authors.affiliation: Laboratoire d'Immunochimie, Hôpital Pitié-Salpêtrière, UPMC, APHP, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Département de radiologie générale, Hôpital Pitié-Salpêtrière, UPMC, APHP, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grenier
authors.affiliation: Département de médecine Interne, Hôpital Universitaire Dijon, Dijon, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Devilliers
authors.affiliation: Département de Médecine Interne et Pathologie Vasculaire, Hôpital Saint Louis, Université Paris 7, APHP, Paris, France.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hij
authors.affiliation: Département d'Immunologie, U905, Université Rouen Normandie, INSERM, Hôpital Universitaire de Rouen, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Herson
authors.affiliation: Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Pathologies Neuromusculaires Paris Est, UPMC, APHP, INSERM, UMR 974, DHU i2B, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000188:drug therapy*; D000069283:Rituximab / Q000627:therapeutic use*; D016896:Treatment Outcome; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab; D003402:Creatine Kinase