title: AA amyloidosis treated with tocilizumab: case series and updated literature review.
abstract: BACKGROUND
  In published case reports, tocilizumab (TCZ) has shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and safety of TCZ in AA amyloidosis in a multicentre study of unselected cases.
  
  
  METHODS
  We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance.
  
  
  RESULTS
  We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 ± 16.2 years, amyloidosis duration 20.6 ± 31.3 months): eight patients had rheumatoid arthritis (RA), six with previous failure of anti-tumor necrosis factor α (anti-TNF-α) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 ± 32.8 mL/min and 5 ± 3.3 g/24 h, respectively. The mean follow-up was 13.1 ± 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-α therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ.
  
  
  CONCLUSIONS
  The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset. Discrepancies between our study of unselected consecutive patients and reported cases may be due to publication bias. These results support further prospective trials of TCZ for AA amyloidosis.
authors.affiliation: Rheumatology Department, Saint-Antoine Hospital, Inserm UMR S_938, UPMC, Univ Paris 06, Assistance Publique-Hôpitaux de Paris (AP-HP), Inflammation-Immunopathology-Biotherapy Departement (DHU i2B) , Paris , France .
authors.forename: Alice
authors.initials: A
authors.lastname: Courties
authors.forename: Gilles
authors.initials: G
authors.lastname: Grateau
authors.forename: Peggy
authors.initials: P
authors.lastname: Philippe
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Flipo
authors.forename: Leonardo
authors.initials: L
authors.lastname: Astudillo
authors.forename: Bérengère
authors.initials: B
authors.lastname: Aubry-Rozier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fabreguet
authors.forename: Wafki
authors.initials: W
authors.lastname: Fahd
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.forename: Pascal
authors.initials: P
authors.lastname: Guggenbuhl
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Thomas
authors.initials: T
authors.lastname: Papo
authors.forename: Christophe
authors.initials: C
authors.lastname: Richez
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Jérémie
authors.initials: J
authors.lastname: Sellam
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy* / Q000473:pathology; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C502936:tocilizumab
keywords: Amyloid A amyloidosis; inflammation; interleukin-6; nephropathy; tocilizumab