RAVE TRIAL SAFETY DATA

No significant difference in overall adverse events occurred between treatment arms at 6 months[18]

Incidence of all adverse events occurring in ≥10% of patients in either treatment arm up to Month 6[18]*

CATEGORY OF
ADVERSE EVENTS
RITUXAN
(n=99); n (%)
CYC FOLLOWED
BY AZA
(n=98); n (%)
CATEGORY OF
ADVERSE EVENTS
RITUXAN
(n=99); n (%)
CYC FOLLOWED
BY AZA
(n=98); n (%)
Nausea 18 (18%) 20 (20%) Fatigue 13 (13%) 21 (21%)
Diarrhea 17 (17%) 12 (12%) Increased ALT 13 (13%) 15 (15%)
Headache 17 (17%) 19 (19%) Hypertension 12 (12%) 5 (5%)
Muscle spasms 17 (17%) 15 (15%) Infusion-related reaction† 12 (12%) 11 (11%)
Anemia 16 (16%) 20 (20%) Epistaxis 11 (11%) 6 (6%)
Peripheral edema 16 (16%) 6 (6%) Dyspnea 10 (10%) 11 (11%)
Insomnia 14 (14%) 12 (12%) Leukopenia 10 (10%) 26 (27%)
Arthralgia 13 (13%) 9 (9%) Rash 10 (10%) 17 (17%)
Cough 13 (13%) 11 (11%)      

ALT, alanine transaminase; AZA, azathioprine; CYC, cyclophosphamide.
*The study design allowed for crossover or treatment by best medical judgment, and 13 patients in each treatment group received a second therapy during the 6-month study period.
Infusion-related reactions in the Rituxan group included cytokine release syndrome, flushing, throat irritation, and tremor.[18]

RAVE Trial: acute infusion reactions* during or within 24 hours of each infusion in the course of therapy

Acute infusion reactions during or within 24 hours of initial course of therapy[10,18]

 AZA, azathioprine; CYC, cyclophosphamide.
*Infusion-related reactions included cytokine release syndrome, flushing, throat irritation, and tremor.

  • Among the 99 patients treated with Rituxan, 12% experienced at least one infusion-related reaction, compared with 11% of the 98 patients in the CYC group[18]
  • Patients were premedicated with antihistamine and acetaminophen before each Rituxan infusion and were on background oral corticosteroids, which may have mitigated or masked an infusion reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of infusion reactions[18]

RAVE Trial: serious adverse events up to 18 months

Adverse events through 18 months[19]

  Rituxan
(n=99)
CYC Followed by AZA
(n=98)
Number of SAEs 59 63
Patients with ≥1 SAE, n (%) 42 (42%) 37 (38%)
Rate of SAEs (per patient-month) 0.04 0.05

AZA, azathioprine; CYC, cyclophosphamide; SAE, serious adverse event.
*Data were censored at time of crossover, initiation of open-label treatment for severe relapse, or a change in treatment according to best medical judgment.

RAVE Trial: infections and serious infections up to Month 6

Infections[18]

Serious Infections[18]

AZA, azathioprine; CYC, cyclophosphamide.

  • Infection was the most common category of adverse events reported[18]
  • The most common infections in the Rituxan group were upper respiratory tract infections, urinary tract infections, and herpes zoster[18]
  • The most common serious infection was pneumonia[18]
  • The rates of serious infections were approximately 25 (Rituxan-treated) and 28 (CYC-treated) per 100 patient-years[18]

MAINRITSAN TRIAL SAFETY PROFILE*

Safety results were consistent with the well-established safety profile of Rituxan across FDA-approved immunologic indications

Rituximab regimen=Roche-manufactured, EU-approved rituximab + GCC.[14]

Infusion reactions[18]
  • 7 patients in the rituximab regimen group (12%) reported infusion-related reactions
  • The incidence of IRR symptoms was highest during or after the first infusion (9%) and decreased with subsequent infusions (<4%)
  • 1 patient had two serious IRRs
  • 2 IRRs led to a dose modification
  • No IRRs were severe, fatal, or led to withdrawal from the study
Infections[18]
  • 30 patients in the rituximab regimen group (53%) reported infections
  • 33 patients in the AZA group (57%) reported infections
  • The incidence of all-grade and serious infections were similar in both arms
  • The most commonly reported serious infection was mild or moderate bronchitis

AZA, azathioprine; EU, European Union; GCC, glucocorticoids; IRR, infusion-related reaction.
*A 28-month, multicenter, randomized, controlled, open-label study of the rituximab regimen versus azathioprine for follow-up treatment in ANCA-associated vasculitis. Investigators used a combined treatment of glucocorticoids and pulse cyclophosphamide to induce disease control. Prednisone treatment was tapered and then kept at a low dose (approximately 5 mg per day) for at least 18 months after randomization. Prednisone dose tapering and the decision to stop prednisone treatment after Month 18 were left to the investigator’s discretion.[18]
There were 44 severe adverse events in the azathioprine group and 45 in the rituximab group. A total of 25 patients in each treatment group had at least 1 severe adverse event.[10,14]
The patient underwent a cholecystectomy[14]
§The patient died[14]
||The infectious diarrhea in one of the patients was caused by campylobacter jejuni [14]
¶The infectious diarrhea was caused by campylobacter jejuni [14]