title: Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial.
abstract: OBJECTIVE
  To explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re-treatment.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once-weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs). Secondary end points were the effects on peripheral blood B cells, disease activity biomarkers, and American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) response rates.
  
  
  RESULTS
  Eighteen patients were randomized to receive atacicept and 9 to receive placebo. AEs occurred in 17 atacicept-treated patients (94.4%) and in all 9 placebo-treated patients (100%). There were no infection-related serious adverse events. Hypersensitivity and injection site reactions were more common, and more patients withdrew due to AEs, in the atacicept group. Median reductions in Ig levels from baseline to week 32 were greater with atacicept (median change in IgG -31.2%, IgM -60.9%, and IgA -56.4%) than with placebo (median change in IgG -4.4%, IgM -15.9%, and IgA -8.2%). Peripheral B cell numbers remained low in all patients after rituximab-mediated B cell depletion, limiting comparison of time to recovery between treatment groups. There were no between-group differences in ACR20, ACR50, and ACR70 response rates.
  
  
  CONCLUSIONS
  In this exploratory trial, atacicept in combination with rituximab showed no new safety issues. Peripheral B cell counts remained too low to determine whether atacicept delayed B cell re-expansion following rituximab-mediated depletion. Despite clear biologic effects, adding atacicept to rituximab in patients with active RA was not associated with clinical benefit.
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: R F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts.
authors.forename: S
authors.initials: S
authors.lastname: Wax
authors.affiliation: EMD Serono, Inc., Rockland, Massachusetts.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands, University of Cambridge, Cambridge, UK, and GlaxoSmithKline, Stevenage, UK.
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; C524618:TACI receptor-IgG Fc fragment fusion protein