Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: A randomized, controlled trial
E. William St. Clair
Duke University Medical Center, Durham, North Carolina
Drs. St.Clair, van der Heijde, Smolen, Maini, Bathon, Emery, Keystone, and Kalden have received consultancies and/or honoraria from Centocor, Inc., totaling less than $10,000 per year. In 2002, Drs. van der Heijde and Maini gave expert testimony to the FDA hearing on inhibition of structural damage and received a fee. The Kennedy Institute of Rheumatology has a patent and a research and licensing agreement from Centocor, Inc., under which it has received royalties for the use of infliximab in rheumatoid arthritis. As a coinventor, Dr. Maini receives a percentage of these royalties under the Kennedy Institute's formula for the division of royalties. Drs. Maini, Wang, DeWoody, Weiss, and Baker own stock in Johnson & Johnson, of which Centocor, Inc., is a subsidiary.
Search for more papers by this authorDésirée M. F. M. van der Heijde
University Hospital Maastricht, Maastricht, The Netherlands
Search for more papers by this authorCorresponding Author
Josef S. Smolen
Medical University of Vienna, Vienna, Austria
Division of Rheumatology, Department of Medicine III, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, AustriaSearch for more papers by this authorRavinder N. Maini
Kennedy Institute of Rheumatology, London, UK
Search for more papers by this authorEdward Keystone
Center for Advanced Therapeutics, Mt. Sinai Hospital, Toronto, Ontario, Canada
Search for more papers by this authorJoachim R. Kalden
Institute for Clinical Immunology, Erlangen, Germany
Search for more papers by this authorActive-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group
Search for more papers by this authorE. William St. Clair
Duke University Medical Center, Durham, North Carolina
Drs. St.Clair, van der Heijde, Smolen, Maini, Bathon, Emery, Keystone, and Kalden have received consultancies and/or honoraria from Centocor, Inc., totaling less than $10,000 per year. In 2002, Drs. van der Heijde and Maini gave expert testimony to the FDA hearing on inhibition of structural damage and received a fee. The Kennedy Institute of Rheumatology has a patent and a research and licensing agreement from Centocor, Inc., under which it has received royalties for the use of infliximab in rheumatoid arthritis. As a coinventor, Dr. Maini receives a percentage of these royalties under the Kennedy Institute's formula for the division of royalties. Drs. Maini, Wang, DeWoody, Weiss, and Baker own stock in Johnson & Johnson, of which Centocor, Inc., is a subsidiary.
Search for more papers by this authorDésirée M. F. M. van der Heijde
University Hospital Maastricht, Maastricht, The Netherlands
Search for more papers by this authorCorresponding Author
Josef S. Smolen
Medical University of Vienna, Vienna, Austria
Division of Rheumatology, Department of Medicine III, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna, AustriaSearch for more papers by this authorRavinder N. Maini
Kennedy Institute of Rheumatology, London, UK
Search for more papers by this authorEdward Keystone
Center for Advanced Therapeutics, Mt. Sinai Hospital, Toronto, Ontario, Canada
Search for more papers by this authorJoachim R. Kalden
Institute for Clinical Immunology, Erlangen, Germany
Search for more papers by this authorActive-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group
Search for more papers by this authorAbstract
Objective
To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti–tumor necrosis factor α [anti-TNFα] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of ≤3 years' duration.
Methods
RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFα 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.
Conclusion
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.
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