title: Prospective study of TNFalpha blockade with adalimumab in ANCA-associated systemic vasculitis with renal involvement.
abstract: BACKGROUND
  Tumour necrosis factor alpha (TNFα) is implicated in the pathogenesis of ANCA-associated systemic vasculitis (AASV). There is a need for more effective and safer induction therapies for AASV. Uncontrolled studies have pointed to the efficacy of TNFα blockade with infliximab in the induction of remission in systemic vasculitides. We have hypothesized that adjunctive treatment with the humanized anti-TNFα monoclonal antibody, adalimumab, will permit more rapid remission and reduced prednisolone exposure in AASV.
  
  
  METHODS
  This Phase II, open-label, prospective study enrolled 14 patients with acute flares of AASV either as first manifestation of disease or relapse. The Birmingham Vasculitis Activity Score (BVAS) was used to assess the activity of the disease and the response to treatment. Adalimumab (40 mg s.c.) was given every 2 weeks for 3 months, in combination with intravenous cyclophosphamide and a reducing course of prednisolone. Primary endpoints were: (i) induction of remission within the first 14 weeks (BVAS = 0); (ii) time taken to achieve remission; (iii) safety and tolerability.
  
  
  RESULTS
  Mean age was 58 years and eight patients were male; all had kidney involvement. Eleven (78.5%) achieved remission within 14 weeks (mean, 12 weeks). BVAS decreased from 11.9 (mean; 95% CI, 9.3-14.4) at baseline to 2.0 (mean; 95% CI, 0-4.4) at Week 14 (P < 0.01). Prednisolone dose (in milligrammes per day) decreased from 37.1 (mean; 95% CI, 28.8-45.3) at entry to 8.1 (mean; 95% CI, 5.1-11.1) at Week 14 (P < 0.01). Estimated glomerular filtration rate (in millilitres per minute per 1.73 m(2)) increased from 17.1 (mean; 95% CI, 8.9-25.2) at entry to 30.1 (mean; 95% CI, 18-42.2) at 12 weeks (P < 0.01). One patient died and three infections occurred.
  
  
  CONCLUSIONS
  The addition of adalimumab to prednisolone and cyclophosphamide for the treatment of severe AASV was associated with response rates and adverse events similar to standard therapy alone but with a reduced prednisolone exposure. Further study is required to demonstrate whether the addition of adalimumab improves the speed of remission, the degree of renal recovery and safety.
authors.affiliation: Department of Nephrology and Dialysis, Second University of Naples, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Laurino
authors.forename: Afzal
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Anthony
authors.initials: A
authors.lastname: Booth
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: David
authors.initials: D
authors.lastname: Jayne
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy* / Q000503:physiopathology; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D011239:Prednisolone; D000068879:Adalimumab