RESEARCH - Requirement of MTX in combination with anti-TNF-alpha therapy for adequate suppression of osteoclastogenesis in RA

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J Rheumatol. 2007 Dec;34(12):2326-33. Epub 2007 Nov 15.

Requirement of methotrexate in combination with anti-tumor necrosis

factor-alpha therapy for adequate suppression of osteoclastogenesis in

rheumatoid arthritis.

Matsuno H, Yoshida K, Ochiai A, Okamoto M.

Matsuno Clinic for Rheumatic Diseases, Toyama, Japan.

OBJECTIVE: To determine that concomitant use of methotrexate (MTX) is

required to achieve adequate suppression of bone destruction in

treating rheumatoid arthritis (RA) with tumor necrosis factor-alpha

(TNF-alpha)-inhibiting biologic therapy. We quantitatively compared

the suppressive effects of treatment with a combination of infliximab

and MTX and treatment with each of these 2 agents alone on bone

destruction in SCID-HuRAg-pit mice. METHODS: Tissue derived from human

RA pannus was implanted with a slice of dentin subcutaneously in the

backs of SCID mice (SCID-HuRAg-pit model). Infliximab was administered

daily to SCID-HuRAg-pit mice using an osmotic pump for 2 weeks with or

without oral administration of MTX. Histological changes in tissue and

the pits formed on the dentin slice were examined 8 weeks after

transplant. Serum concentrations of TNF-alpha and interleukin 6 (IL-6)

were also measured. RESULTS: Treatment with a combination of

infliximab and MTX suppressed pit formation significantly, while

treatment with neither infliximab alone nor MTX alone had a

significant effect on pit formation. Synovial inflammation and serum

TNF-alpha and IL-6 levels were suppressed by infliximab with or

without MTX.

CONCLUSION: This is the first evidence in an animal model of arthritis

that concomitant use of MTX is required to achieve adequate

suppression of bone destruction when treating RA with a

TNF-alpha-inhibiting biologic. Our findings suggest that infliximab

suppresses bone destruction through a mechanism of action different

from that mediating its antiinflammatory effects in the treatment of

RA.

PMID: 18050387

http://www.ncbi.nlm.nih.gov/pubmed/18050387

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