Drs. Breedveld, Furst, van der Heijde, Kalden, Maini, Smolen, St.Clair, and Weisman have received consultancies and/or honoraria from Centocor, Inc. Drs. Marsters and Maini have stock ownership or options in Centocor, Inc. In 2002, Dr. Maini received a fee for giving expert testimony to the FDA during a hearing on inhibition of structural damage. The Kennedy Institute of Rheumatology has a patent and a research and licensing agreement from Centocor, Inc., for the use of infliximab in rheumatoid arthritis, for which it has received royalties. As co-inventor, Dr. Maini receives a percentage of the royalties.
Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate†
Article first published online: 5 APR 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 4, pages 1051–1065, April 2004
How to Cite
Maini, R. N., Breedveld, F. C., Kalden, J. R., Smolen, J. S., Furst, D., Weisman, M. H., St.Clair, E. W., Keenan, G. F., van der Heijde, D., Marsters, P. A. and Lipsky, P. E. (2004), Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis & Rheumatism, 50: 1051–1065. doi: 10.1002/art.20159
- Issue published online: 5 APR 2004
- Article first published online: 5 APR 2004
- Manuscript Accepted: 7 JAN 2004
- Manuscript Received: 3 OCT 2002
- Centocor, Inc., Malvern, Pennsylvania
To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX.
Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms).
The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P ≤ 0.006) and SF-36 physical component summary scores (P ≤ 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group.
Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.