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  1. R. Smith1,
  2. D. Jayne2,
  3. P. A. Merkel3
  4. on behalf of RITAZAREM Investigators
  1. 1University of Cambridge, Department of Medicine, Cambridge, United Kingdom
  2. 2University of Cambridge, Cambridge, United Kingdom
  3. 3University of Pennsylvania, Philadelphia, United States of America


Background: Rituximab (RTX) is an effective therapy for induction of remission in ANCA-associated vasculitis (AAV). However, the effect of RTX is not sustained, and subsequent relapse rates are high, especially in patients with a history of relapse.

Objectives: The RITAZAREM trial is an international, multi-center, open-labelled, randomized, controlled trial of patients with AAV with relapsing disease comparing the efficacy, after induction of remission with RTX, of two relapse-prevention strategies: repeat dosing of RTX or daily oral azathioprine (AZA).

Methods: Patients with AAV were recruited at the time of relapse and received induction therapy with RTX and glucocorticoids. If remission was achieved by month 4, patients were randomized in a 1:1 ratio to receive either RTX (1000 mg every 4 months for 5 doses) or AZA (2 mg/kg/day) as maintenance therapy. Patients were followed for a minimum of 36 months, with the primary outcome being time to disease relapse.

Results: 190 patients were enrolled and 170 randomized at 4 months (85 to RTX; 85 to AZA). The data are complete on all patients up to at least month 24. Median age was 59 years (range 19-89), with a prior disease duration of 5.3 years (0.4-38.5). 123/170 (72%) patients had a history of testing positive for anti-proteinase 3 ANCA; 47/170 (28%) for myeloperoxidase ANCA; 104/170 (61%) were enrolled having suffered a major relapse, and 48/170 (28%) received a pre-specified higher dose glucocorticoid induction regimen (Table 1).

Table 1.

Baseline characteristics of patients enrolled in RITAZAREM trial

RTX was superior to AZA in preventing disease relapse with a preliminary overall hazard ratio (HR) estimate of 0.36 (95% CI 0.23-0.57, p <0.001) and a during-treatment HR estimate of 0.30 (95% CI 0.15-0.60, p<0.001) (Figure 1). After adjustment, none of the randomization stratification covariates (ANCA type, glucocorticoid induction regimen, or relapse severity) had a significant differential effect on the primary outcome. By 24 months after entry, 20 months after randomization, 11/85 (13%) patients in the RTX group had experienced a relapse compared to 32/85 (38%) patients in the AZA group. 19/85 (22%) patients in the RTX group and 31/85 (36%) patients in the AZA group experienced at least one severe adverse event (SAE). 25/85 (29%) and 42/85 (49%) patients in the RTX group developed hypogammaglobulinaemia (IgG <5g/l) and non-severe infections respectively, compared to 21/85 (25%) and 41/85 (48%) in the AZA group.

Figure 1.

Relapse-free survival in RITAZAREM trial: rituximab versus azathioprine

Conclusion: In the RITAZAREM trial, following induction of remission with RTX, RTX was superior to AZA for preventing disease relapse in patients with AAV with a prior history of relapse. There were no new major safety signals for use of these medications in this population.

Disclosure of Interests: Rona Smith Grant/research support from: Roche, David Jayne Grant/research support from: ChemoCentryx, GSK, Roche/Genentech, Sanofi-Genzyme, Consultant of: Astra-Zeneca, ChemoCentryx, GSK, InflaRx, Takeda, Insmed, Chugai, Boehringer-Ingelheim, Peter A. Merkel Grant/research support from: AstraZeneca, Bristol-Myers Squibb, Boeringher-Ingelheim, Celgene, ChemoCentryx, Genentech/Roche. Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Kypha, TerumoBCT., Consultant of: AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Boeringher-Ingelheim, Celgene, ChemoCentryx, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Insmed, Jannsen, Sparrow, Kiniksa.

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