PMID- 19180516
OWN - NLM
STAT- MEDLINE
DCOM- 20090401
LR  - 20131121
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 60
IP  - 2
DP  - 2009 Feb
TI  - Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, 
      in a double-blind, methotrexate-controlled study of patients with active 
      rheumatoid arthritis.
PG  - 335-44
LID - 10.1002/art.24266 [doi]
AB  - OBJECTIVE: To determine the efficacy and safety of pamapimod (a selective 
      inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison 
      with methotrexate (MTX) treatment in adult patients with active rheumatoid 
      arthritis (RA). METHODS: Patients were randomly assigned to 1 of 4 treatment 
      groups and received 12 weeks of double-blind treatment. One group received MTX 
      (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received 
      pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the 
      proportion of patients meeting the American College of Rheumatology 20% 
      improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end 
      points included ACR50 and ACR70 responses, change from baseline in the Disease 
      Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European 
      League Against Rheumatism response, and change from baseline in each parameter of 
      the ACR core set of measures. Safety monitoring included recording of adverse 
      events (AEs), laboratory testing, immunology assessments, administration of 
      electrocardiograms, and assessment of vital signs. RESULTS: Patients assigned to 
      receive MTX and pamapimod had similar demographics and baseline characteristics. 
      At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 
      31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients 
      taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs 
      were typically characterized as mild and included infections, skin disorders, and 
      dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared 
      to be more toxic than either the 2 lower doses or MTX. CONCLUSION: The present 
      results showed that pamapimod was not as effective as MTX in the treatment of 
      active RA.
FAU - Cohen, Stanley B
AU  - Cohen SB
AD  - Metroplex Clinical Research, Dallas, Texas 75235, USA. scohen@arthdocs.com
FAU - Cheng, Tien-Tsai
AU  - Cheng TT
FAU - Chindalore, Vishala
AU  - Chindalore V
FAU - Damjanov, Nemanja
AU  - Damjanov N
FAU - Burgos-Vargas, Ruben
AU  - Burgos-Vargas R
FAU - Delora, Patricia
AU  - Delora P
FAU - Zimany, Kathleen
AU  - Zimany K
FAU - Travers, Helen
AU  - Travers H
FAU - Caulfield, John P
AU  - Caulfield JP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidines)
RN  - 8S2C9V11K4 (pamapimod)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Arthritis Rheum. 2009 Feb;60(2):317-20. PMID: 19180514
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/blood/*drug therapy/physiopathology
MH  - C-Reactive Protein/analysis
MH  - Double-Blind Method
MH  - Female
MH  - Health Status
MH  - Humans
MH  - Male
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - Pyridones/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Severity of Illness Index
MH  - Treatment Outcome
MH  - p38 Mitogen-Activated Protein Kinases/*antagonists & inhibitors
EDAT- 2009/01/31 09:00
MHDA- 2009/04/02 09:00
CRDT- 2009/01/31 09:00
PHST- 2009/01/31 09:00 [entrez]
PHST- 2009/01/31 09:00 [pubmed]
PHST- 2009/04/02 09:00 [medline]
AID - 10.1002/art.24266 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2009 Feb;60(2):335-44. doi: 10.1002/art.24266.