Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study)
| Autor: | Andrea Rubbert-Roth, Hans-Peter Tony, Harald Burkhardt, Martin Aringer, Klaus Krueger, Ulf Müller-Ladner, T. Rossmanith, Michaela Koehm, Marina Backhaus, Rieke Alten, Eva Herrmann, Annette Lehn, Eugen Feist, Frank Behrens, Siegfried Wassenberg, Herbert Kellner, Gerd R Burmester |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
rheumatoid arthritis
Male medicine.medical_specialty Placebo law.invention 03 medical and health sciences 0302 clinical medicine rituximab Rheumatology Randomized controlled trial law Internal medicine Clinical endpoint medicine Humans Pharmacology (medical) 030212 general & internal medicine Adverse effect AcademicSubjects/MED00360 investigator-initiated research Leflunomide Aged 030203 arthritis & rheumatology leflunomide business.industry Clinical Science Middle Aged medicine.disease randomized clinical trial Clinical trial Treatment Outcome Rheumatoid arthritis Antirheumatic Agents Rituximab Drug Therapy Combination Female business medicine.drug |
| Zdroj: | Rheumatology (Oxford, England) |
| ISSN: | 1462-0332 1462-0324 |
| Popis: | Objective To investigate the efficacy and safety of rituximab + LEF in patients with RA. Methods In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators’ control. Results Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders. Conclusion The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring. Trial registration EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958. |
| Databáze: | OpenAIRE |
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