PMID- 10902750
OWN - NLM
STAT- MEDLINE
DCOM- 20000808
LR  - 20211203
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 43
IP  - 7
DP  - 2000 Jul
TI  - Inhibition of neutrophil migration soon after initiation of treatment with 
      leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a 
      prospective, randomized, double-blind clinical trial in fifteen patients.
PG  - 1488-95
AB  - OBJECTIVE: Leflunomide is a novel immunomodulating drug that has recently been 
      approved as a disease-modifying antirheumatic drug for the treatment of 
      rheumatoid arthritis (RA). The aim of this study was to determine the 
      relationship between the clinical effects of leflunomide and neutrophil 
      migration. METHODS: The effects of leflunomide and methotrexate on neutrophil 
      chemotaxis were studied in 15 RA patients who participated in a prospective, 
      randomized, double-blind clinical trial. When possible, neutrophil numbers were 
      counted in synovial fluid (SF) samples at baseline and after 14 days, 4 months, 
      and 1 year of treatment. The chemotactic properties of peripheral blood 
      neutrophils from RA patients treated with either leflunomide or methotrexate were 
      studied by the Boyden chamber technique, using the activators 
      formyl-methionyl-leucyl-phenylalanine (fMLP) and interleukin-8 (IL-8). The in 
      vitro effects of A77 1726, the active metabolite of leflunomide, and methotrexate 
      on peripheral blood neutrophils from 7 healthy control subjects were also 
      investigated. RESULTS: Both therapy groups exhibited clinical improvement, 
      including rapid reductions in SF neutrophil counts and reduced joint swelling and 
      tenderness. On day 14, 3 of 7 patients who received leflunomide showed no 
      detectable effusions. There was a significant effect on neutrophil chemotaxis (P 
      < 0.001), which was similar for leflunomide and methotrexate. The direct effects 
      on the neutrophils diminished over time. Incubation of peripheral blood 
      neutrophils from healthy controls with A77 1726 confirmed the inhibitory effect 
      on chemotaxis. CONCLUSION: Leflunomide treatment is beneficial in RA patients. 
      Different mechanisms are operative in various phases of treatment, leading to 
      decreased recruitment of inflammatory cells in the joints.
FAU - Kraan, M C
AU  - Kraan MC
AD  - Department of Clinical Immunology and Rheumatology, Academic Medical Center, 
      Amsterdam, The Netherlands.
FAU - de Koster, B M
AU  - de Koster BM
FAU - Elferink, J G
AU  - Elferink JG
FAU - Post, W J
AU  - Post WJ
FAU - Breedveld, F C
AU  - Breedveld FC
FAU - Tak, P P
AU  - Tak PP
LA  - eng
PT  - Clinical Trial
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 (Aniline Compounds)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Crotonates)
RN  - 0 (Hydroxybutyrates)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-8)
RN  - 0 (Isoxazoles)
RN  - 0 (Nitriles)
RN  - 0 (Toluidines)
RN  - 1C058IKG3B (teriflunomide)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - G162GK9U4W (Leflunomide)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Aniline Compounds/pharmacology
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/blood/*drug therapy
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Crotonates
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Hydroxybutyrates/pharmacology
MH  - Immunosuppressive Agents/*therapeutic use
MH  - In Vitro Techniques
MH  - Interleukin-8/pharmacology
MH  - Isoxazoles/*therapeutic use
MH  - Leflunomide
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/physiology
MH  - Nitriles
MH  - Prospective Studies
MH  - Toluidines
EDAT- 2000/07/21 11:00
MHDA- 2000/08/12 11:00
CRDT- 2000/07/21 11:00
PHST- 2000/07/21 11:00 [pubmed]
PHST- 2000/08/12 11:00 [medline]
PHST- 2000/07/21 11:00 [entrez]
AID - 10.1002/1529-0131(200007)43:7<1488::AID-ANR11>3.0.CO;2-G [doi]
PST - ppublish
SO  - Arthritis Rheum. 2000 Jul;43(7):1488-95. doi: 
      10.1002/1529-0131(200007)43:7<1488::AID-ANR11>3.0.CO;2-G.