Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial.
OBJECTIVE
To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration.


METHODS
RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46.


RESULTS
At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia.


CONCLUSIONS
For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.
St Clair
E William
EW
Duke University Medical Center, Durham, North Carolina, USA.
van der Heijde
Désirée M F M
DM
Smolen
Josef S
JS
Maini
Ravinder N
RN
Bathon
Joan M
JM
Emery
Paul
P
Keystone
Edward
E
Schiff
Michael
M
Kalden
Joachim R
JR
Wang
Ben
B
Dewoody
Kimberly
K
Weiss
Roberta
R
Baker
Daniel
D
D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001175:Arthrography; D015551:Autoimmunity; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D020127:Recovery of Function; D016896:Treatment Outcome
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D008727:Methotrexate