Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: results from the RATE-RA study

Abstract

BackgroundAs recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25 hours for the first infusion and 3.25 hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2 hours in patients with RA.MethodsPatients with an inadequate response to anti-TNF who were rituximab-naive or -experienced received 2 courses of rituximab: Infusion 1 (Day 1) was administered over the standard 4.25 hours, and Infusions 2 (Day 15), 3 (Day 168) and 4 (Day 182) were administered over a faster 2-hour period. The primary endpoint was incidence of infusion-related reactions (IRRs) associated with Infusion 2.ResultsOf the 351 patients enrolled, 87% and 13% were rituximab-naive and -experienced, respectively. The incidence (95% CI) of IRRs associated with Infusion 1 was 16.2% (12.5%, 20.5%) and consistent with weighted historical incidence of 20.7% (19.4%, 22.1%). The incidence (95% CI) of IRRs associated with Infusions 2, 3, and 4 compared with respective weighted historical incidences at the standard infusion rate was 6.5% (4.1%, 9.7%) vs 8.1% (7.2%, 9.1%); 5.9% (3.5%, 9.3%) vs 11.5% (10.3%, 12.8%); and 0.7 (0.1%, 2.6%) vs 5.0% (4.2%, 6.0%), respectively. All IRRs were grade 1 or 2, except for 3 grade 3 IRRs associated with Infusion 1 and 2 grade 3 IRRs associated with Infusion 2. Four patients experienced a total of 5 grade 3 IRRs; 3 of these patients continued on to received subsequent infusions at the faster rate. There were no serious IRRs.ConclusionThis study demonstrated that rituximab can be administered at the faster infusion rate at the second and subsequent infusions without increasing the rate or severity of IRRs.

The Efficacy and Safety of Rituximab in Rheumatoid Arthritis: New Evidence

“…В исследовании RATE-RA [45] частота инфузионных реакций (ИР) составляла 16,2% (95% ДИ 12,5-20,5%) при сравнении с данными открытых РКИ, скорректированных на долю пациентов исходно, с одним и двумя предшеству-ющими курсами РТМ -20,7% (95% ДИ 19,4-22,1%). Ин-фузии 2-я (15-й день), 3-я (168-й день), 4-я (182-й день) проводились в течение 2 ч. Из 337 пациентов, получивших инфузию с более высокой скоростью, 22 (6,5%; 95% ДИ 4,1-9,7%) имели в общей сложности 30 ИР, тошнота (1,2%) и озноб (0,9%) были наиболее распространенными реак-циями, что сходно со скорректированными данными -8,1% (95% ДИ 7,2-9,1%) при стандартной скорости инфу-зии.…”

Rituximab for Rheumatoid Arthritis

“…Lastly, as currently recommended, rituximab infusion requires 4.25 h for the initial infusion and 3.25 h for subsequent infusions. This regimen is based on the rituximab usage in non-Hodgkins lymphoma, where the incidence of IRR is much higher than that observed in RA [ 76 ]. Long infusion times and frequent infusion rate changes are not only inconvenient but increase infusion center costs.…”

“…Long infusion times and frequent infusion rate changes are not only inconvenient but increase infusion center costs. Several studies have attempted to increase the rate of rituximab infusion after the initial infusion, with reported success [ 76 – 80 ]. In a recent study, infusion over 2 h was well tolerated and not associated with an increased rate of IRR [ 76 ].…”

B-Zell-Therapie mit Rituximab bei rheumatoider Arthritis

“…Dieses seit Mai 2014 zugelassene verkürzte Infusionsschema beruht auf den Daten der prospektiven, offen geführten und multizentrischen RATE-RA-Studie, die die Sicherheit von RTX in verkürz-ter Infusionsgeschwindigkeit über 2 h bei 351 Patienten mit moderater bis schwerer aktiver RA und unzureichendem Ansprechen auf mindestens einen TNF-Hemmer evaluierte [20]. Mit dem verkürz-ten Infusionsschema ließ sich die Infusionszeit ab der zweiten Infusion des ersten Kurs verglichen mit dem bisherigen Schema bei vergleichbarer Inzidenz infusionsbedingter Reaktionen deutlich reduzieren (.…”

“…Abb. 3, [20]). Eine verkürz-te Infusion über 2 h ist nur für eine Konzentration von 4 mg/ml zugelassen (Volumen von 250 ml), die Prämedikation entspricht der des bisherigen Schemas [9].…”