Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.
OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid...
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Lenguaje: | English |
| Publicado: |
1998
|
| _version_ | 1826292719720333312 |
|---|---|
| author | Maini, R Breedveld, F Kalden, JR Smolen, J Davis, D Macfarlane, J Antoni, C Leeb, B Elliott, M Woody, J Schaible, T Feldmann, M |
| author_facet | Maini, R Breedveld, F Kalden, JR Smolen, J Davis, D Macfarlane, J Antoni, C Leeb, B Elliott, M Woody, J Schaible, T Feldmann, M |
| author_sort | Maini, R |
| collection | OXFORD |
| description | OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha 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 approximately 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 approximately 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. |
| first_indexed | 2024-03-07T03:19:03Z |
| format | Journal article |
| id | oxford-uuid:b6cd2920-1f1e-459a-a290-55e23d9d26e6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:19:03Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:b6cd2920-1f1e-459a-a290-55e23d9d26e62022-03-27T04:43:41ZTherapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b6cd2920-1f1e-459a-a290-55e23d9d26e6EnglishSymplectic Elements at Oxford1998Maini, RBreedveld, FKalden, JRSmolen, JDavis, DMacfarlane, JAntoni, CLeeb, BElliott, MWoody, JSchaible, TFeldmann, MOBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha 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 approximately 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 approximately 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. |
| spellingShingle | Maini, R Breedveld, F Kalden, JR Smolen, J Davis, D Macfarlane, J Antoni, C Leeb, B Elliott, M Woody, J Schaible, T Feldmann, M Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title | Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title_full | Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title_fullStr | Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title_full_unstemmed | Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title_short | Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. |
| title_sort | therapeutic efficacy of multiple intravenous infusions of anti tumor necrosis factor alpha monoclonal antibody combined with low dose weekly methotrexate in rheumatoid arthritis |
| work_keys_str_mv | AT mainir therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT breedveldf therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT kaldenjr therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT smolenj therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT davisd therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT macfarlanej therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT antonic therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT leebb therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT elliottm therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT woodyj therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT schaiblet therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis AT feldmannm therapeuticefficacyofmultipleintravenousinfusionsofantitumornecrosisfactoralphamonoclonalantibodycombinedwithlowdoseweeklymethotrexateinrheumatoidarthritis |