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Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 w...

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Autores principales: Koehm, Michaela, Foldenauer, Ann C., Rossmanith, Tanja, Alten, Rieke, Aringer, Martin, Backhaus, Marina, Burmester, Gerd R., Feist, Eugen, Kellner, Herbert, Krueger, Klaus, Müller-Ladner, Ulf, Rubbert-Roth, Andrea, Tony, Hans-Peter, Wassenberg, Siegfried, Burkhardt, Harald, Behrens, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784147/
https://www.ncbi.nlm.nih.gov/pubmed/36555933
http://dx.doi.org/10.3390/jcm11247316
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author Koehm, Michaela
Foldenauer, Ann C.
Rossmanith, Tanja
Alten, Rieke
Aringer, Martin
Backhaus, Marina
Burmester, Gerd R.
Feist, Eugen
Kellner, Herbert
Krueger, Klaus
Müller-Ladner, Ulf
Rubbert-Roth, Andrea
Tony, Hans-Peter
Wassenberg, Siegfried
Burkhardt, Harald
Behrens, Frank
author_facet Koehm, Michaela
Foldenauer, Ann C.
Rossmanith, Tanja
Alten, Rieke
Aringer, Martin
Backhaus, Marina
Burmester, Gerd R.
Feist, Eugen
Kellner, Herbert
Krueger, Klaus
Müller-Ladner, Ulf
Rubbert-Roth, Andrea
Tony, Hans-Peter
Wassenberg, Siegfried
Burkhardt, Harald
Behrens, Frank
author_sort Koehm, Michaela
collection PubMed
description Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Results: Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Conclusions: Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity.
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spelling pubmed-97841472022-12-24 Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA) Koehm, Michaela Foldenauer, Ann C. Rossmanith, Tanja Alten, Rieke Aringer, Martin Backhaus, Marina Burmester, Gerd R. Feist, Eugen Kellner, Herbert Krueger, Klaus Müller-Ladner, Ulf Rubbert-Roth, Andrea Tony, Hans-Peter Wassenberg, Siegfried Burkhardt, Harald Behrens, Frank J Clin Med Article Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known. Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide. In the study reported here (Part 2), Part 1 responders received rituximab 500 or 1000 mg at W24/26 plus ongoing leflunomide. Patients were randomized at baseline to their eventual W24 treatment group. The Part 2 primary outcome was the mean Disease Activity Score-28 joints (DAS28) at W52, based on the last observation carried forward (LOCF) analyses and a two-sided analysis of variance. Patient-reported outcomes (PROs) and adverse events were evaluated. Results: Eighty-three patients received rituximab at W24/26 (31 rituximab→rituximab 1000 mg; 29 rituximab→rituximab 500 mg; 10 placebo→rituximab 1000 mg; 13 placebo→rituximab 500 mg). At W52, there were no significant differences in DAS28 between rituximab doses in patients originally treated with rituximab or those originally treated with placebo. In the Part 1 placebo group, the higher rituximab dose was associated with greater improvements in ACR response rates and some PROs. Adverse events were similar regardless of rituximab dose. Conclusions: Retreatment with rituximab 500 mg and 1000 mg showed comparable efficacy, whereas an initial dose of rituximab 500 mg was associated with lower response rates versus 1000 mg. Reduced treatment response with the lower dose in patients initially treated with placebo may have been influenced by small numbers and baseline disease activity. MDPI 2022-12-09 /pmc/articles/PMC9784147/ /pubmed/36555933 http://dx.doi.org/10.3390/jcm11247316 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koehm, Michaela
Foldenauer, Ann C.
Rossmanith, Tanja
Alten, Rieke
Aringer, Martin
Backhaus, Marina
Burmester, Gerd R.
Feist, Eugen
Kellner, Herbert
Krueger, Klaus
Müller-Ladner, Ulf
Rubbert-Roth, Andrea
Tony, Hans-Peter
Wassenberg, Siegfried
Burkhardt, Harald
Behrens, Frank
Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title_full Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title_fullStr Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title_full_unstemmed Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title_short Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA)
title_sort effectiveness of different rituximab doses combined with leflunomide in the treatment or retreatment of rheumatoid arthritis: part 2 of a randomized, placebo-controlled, investigator-initiated clinical trial (amara)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784147/
https://www.ncbi.nlm.nih.gov/pubmed/36555933
http://dx.doi.org/10.3390/jcm11247316
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