PMID- 26137975
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20220410
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 67
IP  - 11
DP  - 2015 Nov
TI  - 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.
PG  - 2828-36
LID - 10.1002/art.39262 [doi]
AB  - 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. CONCLUSION: 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.
CI  - (c) 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, 
      Inc. on behalf of the American College of Rheumatology.
FAU - van Vollenhoven, R F
AU  - van Vollenhoven RF
AD  - Karolinska Institute, Stockholm, Sweden.
FAU - Wax, S
AU  - Wax S
AD  - EMD Serono, Inc., Rockland, Massachusetts.
FAU - Li, Y
AU  - Li Y
AD  - EMD Serono, Inc., Rockland, Massachusetts.
FAU - Tak, P P
AU  - Tak PP
AD  - Academic Medical Center and University of Amsterdam, Amsterdam, The Netherlands, 
      University of Cambridge, Cambridge, UK, and GlaxoSmithKline, Stevenage, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT00664521
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - K3D9A0ICQ3 (TACI receptor-IgG Fc fragment fusion protein)
SB  - IM
MH  - Aged
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/adverse effects/*therapeutic use
MH  - Rituximab/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC5057363
EDAT- 2015/07/04 06:00
MHDA- 2016/02/03 06:00
PMCR- 2016/10/11
CRDT- 2015/07/04 06:00
PHST- 2015/01/14 00:00 [received]
PHST- 2015/06/23 00:00 [accepted]
PHST- 2015/07/04 06:00 [entrez]
PHST- 2015/07/04 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2016/10/11 00:00 [pmc-release]
AID - ART39262 [pii]
AID - 10.1002/art.39262 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2015 Nov;67(11):2828-36. doi: 10.1002/art.39262.