PMID- 25359150
OWN - NLM
STAT- MEDLINE
DCOM- 20150811
LR  - 20211021
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 16
IP  - 5
DP  - 2014 Oct 30
TI  - Efficacy and safety of pateclizumab (anti-lymphotoxin-alpha) compared to adalimumab 
      in rheumatoid arthritis: a head-to-head phase 2 randomized controlled study (The 
      ALTARA Study).
PG  - 467
LID - 10.1186/s13075-014-0467-3 [doi]
LID - 467
AB  - INTRODUCTION: Tumor necrosis factor (TNF) and, possibly, lymphotoxin alpha (LTalpha) 
      signaling contribute to inflammation and rheumatoid arthritis (RA) pathogenesis. 
      Pateclizumab (anti-lymphotoxin- alpha; MLTA3698A) is a humanized monoclonal 
      antibody that blocks and depletes anti-LTalpha. This phase 2, randomized, 
      head-to-head, active- and placebo-controlled trial examined the safety and 
      efficacy of pateclizumab compared to adalimumab in RA patients with an inadequate 
      response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS: Patients 
      (n = 214) with active RA (>/= 6 swollen and tender joints, C-reactive protein >/= 10 
      mg/L) on oral DMARDs were randomized (2:2:1) to receive pateclizumab 360 mg, 
      adalimumab 40 mg, or placebo subcutaneously every 2 weeks. The primary endpoint, 
      4-variable, 28-joint disease activity score erythrocyte sedimentation rate 
      (DAS28(4)-ESR) response, was evaluated at 12 weeks using an analysis of 
      covariance (ANCOVA) model with adjustments for concomitant DMARD use and 
      geographic region. Secondary efficacy endpoints included American College of 
      Rheumatology (ACR) 20, ACR50, and ACR70 responses at Day 85. Pharmacokinetics, 
      pharmacodynamics, and immunogenicity of pateclizumab were assessed. RESULTS: 
      Pateclizumab reduced the DAS28(4)-ESR response (-1.89) at 12 weeks, however, this 
      did not reach statistical significance compared to placebo (-1.54), while 
      adalimumab (-2.52) differed significantly from both placebo and pateclizumab. 
      Pateclizumab 12-week ACR20, ACR50 and ACR70 response rates (64%, 33%, and 14%) 
      suggested clinical activity but were not statistically significant compared to 
      placebo rates (46%, 24%, and 8%, respectively). CXCL13 serum levels decreased 
      significantly following pateclizumab and adalimumab administration, demonstrating 
      pharmacological target engagement by both drugs. Overall, adverse events (AEs) 
      were comparable among all cohorts. Infections were the most common AE, occurring 
      with comparable frequency in all groups. Serious AEs occurred in 0% of 
      pateclizumab, 5.9% of adalimumab, and 2.3% of placebo patients, with serious 
      infection in 2.3% of adalimumab patients and none in pateclizumab and placebo 
      patients. CONCLUSIONS: Pateclizumab had a good safety profile in patients 
      inadequately responsive to DMARDs, but no statistically significant improvement 
      in RA signs and symptoms after 12 weeks of treatment. Adalimumab demonstrated 
      efficacy and safety comparable to published results in this head-to-head 
      comparison in DMARD-IR RA patients. TRIAL REGISTRATION: ClinicalTrials.gov 
      NCT01225393, Registered 18 October 2010.
FAU - Kennedy, William P
AU  - Kennedy WP
FAU - Simon, J Abraham
AU  - Simon JA
FAU - Offutt, Carolyn
AU  - Offutt C
FAU - Horn, Priscilla
AU  - Horn P
FAU - Herman, Ann
AU  - Herman A
FAU - Townsend, Michael J
AU  - Townsend MJ
FAU - Tang, Meina T
AU  - Tang MT
FAU - Grogan, Jane L
AU  - Grogan JL
FAU - Hsieh, Frank
AU  - Hsieh F
FAU - Davis, John C
AU  - Davis JC
LA  - eng
SI  - ClinicalTrials.gov/NCT01225393
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141030
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (CXCL13 protein, human)
RN  - 0 (Chemokine CXCL13)
RN  - 0 (Lymphotoxin-alpha)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - FYS6T7F842 (Adalimumab)
RN  - QOK1YYH7J2 (pateclizumab)
SB  - IM
MH  - Adalimumab
MH  - Adolescent
MH  - Adrenal Cortex Hormones/therapeutic use
MH  - Adult
MH  - Aged
MH  - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/pharmacokinetics/*therapeutic 
      use
MH  - Antirheumatic Agents/adverse effects/pharmacokinetics/therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy/metabolism/pathology
MH  - Blood Sedimentation
MH  - C-Reactive Protein/metabolism
MH  - Chemokine CXCL13/genetics/metabolism
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Female
MH  - Headache/chemically induced
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Lymphotoxin-alpha/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Pharyngitis/chemically induced
MH  - Severity of Illness Index
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC4243296
EDAT- 2014/11/02 06:00
MHDA- 2015/08/12 06:00
PMCR- 2014/10/30
CRDT- 2014/11/01 06:00
PHST- 2014/06/03 00:00 [received]
PHST- 2014/10/10 00:00 [accepted]
PHST- 2014/11/01 06:00 [entrez]
PHST- 2014/11/02 06:00 [pubmed]
PHST- 2015/08/12 06:00 [medline]
PHST- 2014/10/30 00:00 [pmc-release]
AID - s13075-014-0467-3 [pii]
AID - 467 [pii]
AID - 10.1186/s13075-014-0467-3 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2014 Oct 30;16(5):467. doi: 10.1186/s13075-014-0467-3.