title: Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study.
abstract: BACKGROUND
  Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20 monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may potentially modify the active inflammatory phase of thyroid-associated ophthalmopathy (TAO).
  
  
  METHODS
  Nine patients with GD, (seven with active TAO, two with mild lid signs) were studied. The trial was only approved as an open pilot study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v. twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was assessed by the clinical activity score (CAS) and severity was classified using NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement; Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss). Thyroid function and lymphocyte count were measured by standardized methods.
  
  
  RESULTS
  All patients attained peripheral B-cell depletion with the first RTX infusion. Minor side effects were reported in three patients. Thyroid function was not affected by RTX therapy and hyperthyroid patients required therapy with methimazole. After RTX, the changes in the levels of thyroglobulin antibodies, thyroperoxidase antibodies and TRAb were neither significant nor correlated with CD20+ depletion (P = NS). CAS values before RTX were 4.7 +/- 0.5 and decreased to 1.8 +/- 0.8 at the end of follow-up (P < 0.0001) and more significantly compared with IVGC (P < 0.05). Proptosis decreased significantly after RTX both in patients with active TAO (ANOVA; P < 0.0001) and those with lid signs (ANOVA; P < 0.003). The degree of inflammation (class 2) decreased significantly in response to RTX (ANOVA; P < 0.001). Relapse of active TAO was not observed in patients treated with RTX, but occurred in 10% of those treated with IVGC, who also experienced adverse effects more frequently (45 vs 33% of patients).
  
  
  CONCLUSIONS
  RTX positively affects the clinical course of TAO, independently of either thyroid function or circulating antithyroid antibodies, including TRAb. If our findings are confirmed in large controlled studies, RTX may represent a useful therapeutic tool in patients with active TAO.
authors.affiliation: Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore IRCCS, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salvi
authors.forename: Guia
authors.initials: G
authors.lastname: Vannucchi
authors.forename: Irene
authors.initials: I
authors.lastname: Campi
authors.forename: Nicola
authors.initials: N
authors.lastname: Currò
authors.forename: Davide
authors.initials: D
authors.lastname: Dazzi
authors.forename: Simona
authors.initials: S
authors.lastname: Simonetta
authors.forename: Paola
authors.initials: P
authors.lastname: Bonara
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.forename: Clara
authors.initials: C
authors.lastname: Sina
authors.forename: Claudio
authors.initials: C
authors.lastname: Guastella
authors.forename: Roberto
authors.initials: R
authors.lastname: Ratiglia
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D005260:Female; D006111:Graves Disease / Q000188:drug therapy*; D049970:Graves Ophthalmopathy / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D013963:Thyroid Hormones; D000069283:Rituximab; D008775:Methylprednisolone