Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study).
Rheumatology (Oxford)
; 60(11): 5318-5328, 2021 11 03.
Article
em En
| MEDLINE
| ID: mdl-33738492
ABSTRACT
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 21 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.Palavras-chave
Texto completo:
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Eixos temáticos:
Pesquisa_clinica
Base de dados:
MEDLINE
Assunto principal:
Antirreumáticos
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Rituximab
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Leflunomida
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article