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Therapeutic efficacy of multiple intravenous infusions of anti‐tumor necrosis factor α monoclonal antibody combined with low‐dose weekly methotrexate in rheumatoid arthritis

Therapeutic efficacy of multiple intravenous infusions of anti‐tumor necrosis factor α monoclonal... Objective To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti‐tumor necrosis factor α antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low‐dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. Methods In a 26‐week, double‐blind, placebo‐controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low‐dose MTX were randomized to 1 of 7 groups of 14‐15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. Results Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P = 0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P = 0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P = 0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low‐dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70‐90% reduction in the swollen joint count, tender joint count, and C‐reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in ∼50% of the patients. Conclusion Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in ∼60% of patients with active RA despite therapy with low‐dose MTX. When cA2 at 1 mg/kg was given with low‐dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer‐term treatment with cA2. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arthritis & Rheumatism Wiley

Therapeutic efficacy of multiple intravenous infusions of anti‐tumor necrosis factor α monoclonal antibody combined with low‐dose weekly methotrexate in rheumatoid arthritis

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References (35)

Publisher
Wiley
Copyright
Copyright © 1998 by the American College of Rheumatology
ISSN
0004-3591
eISSN
1529-0131
DOI
10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W
pmid
9751087
Publisher site
See Article on Publisher Site

Abstract

Objective To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti‐tumor necrosis factor α antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low‐dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. Methods In a 26‐week, double‐blind, placebo‐controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low‐dose MTX were randomized to 1 of 7 groups of 14‐15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. Results Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P = 0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P = 0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P = 0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low‐dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70‐90% reduction in the swollen joint count, tender joint count, and C‐reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in ∼50% of the patients. Conclusion Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in ∼60% of patients with active RA despite therapy with low‐dose MTX. When cA2 at 1 mg/kg was given with low‐dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer‐term treatment with cA2.

Journal

Arthritis & Rheumatism – Wiley

Published: Sep 1, 1998

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