PMID- 28941216
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20180119
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Linking)
VI  - 69
IP  - 12
DP  - 2017 Dec
TI  - Safety, Tolerability, and Pharmacodynamics of ABT-122, a Tumor Necrosis Factor- 
      and Interleukin-17-Targeted Dual Variable Domain Immunoglobulin, in Patients With 
      Rheumatoid Arthritis.
PG  - 2283-2291
LID - 10.1002/art.40319 [doi]
AB  - OBJECTIVE: Tumor necrosis factor (TNF) and interleukin-17 (IL-17) independently 
      contribute to the pathophysiology of rheumatoid arthritis (RA). ABT-122 is a 
      novel dual variable domain immunoglobulin that selectively and simultaneously 
      targets human TNF and IL-17A. The aim of treatment with ABT-122 is to evoke a 
      greater clinical response than that achieved by targeting either cytokine alone. 
      This study was undertaken to present the pooled safety, tolerability, and 
      exploratory pharmacodynamics of ABT-122 based on 2 phase I, placebo-controlled, 
      multiple ascending-dose studies in patients with primarily inactive RA. METHODS: 
      Patients (n = 44) receiving stable dosages of methotrexate (2.5-25 mg/week) were 
      randomized to receive subcutaneous placebo, ABT-122 1 mg/kg every other week (4 
      doses), or ABT-122 0.5, 1.5, or 3 mg/kg weekly (8 doses) and were evaluated 
      through 45 days after the last dose (day 92). Serum samples for the assessment of 
      inflammation markers and chemokines were collected at baseline and on postdose 
      days 3, 5, 8, 15, 29, 57, 64, 78, and 92. RESULTS: No clinically significant 
      findings regarding the safety of ABT-122 were observed. The rates of 
      treatment-emergent adverse events (AEs) were similar in patients receiving 
      ABT-122 and those receiving placebo. Only 1 serious AE (and no systemic 
      hypersensitivity reactions or dose-limiting toxicities) was observed in patients 
      treated with ABT-122. The incidence of infections was similar between patients 
      treated with ABT-122 and those receiving placebo, with no serious infection 
      reported. The levels of CXCL9, CXCL10, CCL23, and soluble E-selectin were 
      significantly decreased following ABT-122 treatment relative to placebo 
      treatment. Although patients had essentially inactive RA, exploratory clinical 
      parameters suggested potential antiinflammatory effects following treatment with 
      ABT-122. CONCLUSION: The results of these phase I studies suggest that dual 
      neutralization of TNF and IL-17 with ABT-122 has characteristics acceptable for 
      further exploration of therapeutic potential in TNF- and IL-17A-driven 
      immune-mediated inflammatory diseases.
CI  - (c) 2017, American College of Rheumatology.
FAU - Fleischmann, Roy M
AU  - Fleischmann RM
AD  - University of Texas Southwestern Medical Center at Dallas.
FAU - Wagner, Frank
AU  - Wagner F
AD  - Charite Research Organisation, Berlin, Germany.
FAU - Kivitz, Alan J
AU  - Kivitz AJ
AD  - Altoona Center for Clinical Research, Duncansville, Pennsylvania.
FAU - Mansikka, Heikki T
AU  - Mansikka HT
AD  - AbbVie, North Chicago, Illinois.
FAU - Khan, Nasser
AU  - Khan N
AD  - AbbVie, North Chicago, Illinois.
FAU - Othman, Ahmed A
AU  - Othman AA
AD  - AbbVie, North Chicago, Illinois.
FAU - Khatri, Amit
AU  - Khatri A
AD  - AbbVie, North Chicago, Illinois.
FAU - Hong, Feng
AU  - Hong F
AD  - AbbVie, Worcester, Massachusetts.
FAU - Jiang, Ping
AU  - Jiang P
AD  - AbbVie, North Chicago, Illinois.
FAU - Ruzek, Melanie
AU  - Ruzek M
AD  - AbbVie, Worcester, Massachusetts.
FAU - Padley, Robert J
AU  - Padley RJ
AD  - AbbVie, North Chicago, Illinois.
LA  - eng
SI  - ClinicalTrials.gov/NCT01853033
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20171108
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (ABT-122)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (CCL23 protein, human)
RN  - 0 (CXCL10 protein, human)
RN  - 0 (CXCL9 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chemokine CXCL9)
RN  - 0 (Chemokines, CC)
RN  - 0 (E-Selectin)
RN  - 0 (IL17A protein, human)
RN  - 0 (Immunoglobulins)
RN  - 0 (Interleukin-17)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antirheumatic Agents/*pharmacology
MH  - Arthritis, Rheumatoid/blood/*drug therapy
MH  - Chemokine CXCL10/blood/drug effects
MH  - Chemokine CXCL9/blood/drug effects
MH  - Chemokines, CC/blood/drug effects
MH  - Double-Blind Method
MH  - E-Selectin/blood/drug effects
MH  - Female
MH  - Humans
MH  - Immunoglobulins/*pharmacology
MH  - Interleukin-17/*blood
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/blood/*drug effects
MH  - Young Adult
EDAT- 2017/09/25 06:00
MHDA- 2017/12/12 06:00
CRDT- 2017/09/24 06:00
PHST- 2017/01/25 00:00 [received]
PHST- 2017/09/06 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
AID - 10.1002/art.40319 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2017 Dec;69(12):2283-2291. doi: 10.1002/art.40319. Epub 2017 
      Nov 8.