Table 2.
Summary of Included Studies of ANCA-Associated Vasculitis (Listed in Chronological Order According to Type of Study).
| Study | Type | Intervention/aim | Number of participants | RTX regimen | Concomitant immunosuppression | B-cell depletion reported | Study duration | Primary findings | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| Induction regimen | |||||||||
| Stone et al6
USA & Europe |
RCT | RTX vs CYC for the induction of CR for severe AAV | 197 | 4 doses of 375 mg/m2/wk | GC for induction and maintenance AZA for maintenance |
Yes | 6 months | CR: RTX group: 63 (64%) Control: 52 (53%) P < .001 for noninferiority |
AE: RTX: 1035, Control: 1061 SAE: RTX: 79, Control: 78 |
| Jones et al7
Europe and Australia |
RCT | RTX vs CYC-based regimens for renal AAV | 44 | 4 doses of 375 mg/m2/wk | Two doses of IV CYC for induction and GC for induction
and maintenance PLEX use was allowed before enrolment |
Yes | 12 months | Sustained remission: RTX group: 25/33 (76%) Control: 9/11 (82%) (P = .68) |
AE: RTX: 68 Control: 26 SAE: RTX: 31 Control: 12 |
| Furuta et al8
Japan |
RCT | Compare efficacy and safety of reduced-dose vs standard-dose GC, plus RTX (both groups), in remission induction of AAV | 140 | 4 doses of 375 mg/m2/wk | GC (low vs high dose) | Yes | 6 months | Remission: Reduced GC group: 49/69 patients (71%) High GC group: 45/65 patients (69%) P = .003 for noninferiority |
AE: Not mentioned SAE: Low GC: 21 High GC: 41 |
| Mansfield et al9
UK |
PCS | RTX and CYC for induction of remission for renal AAV | 23 | 1000 mg on days 0, 14 | Induction: IV CYC and oral GC Maintenance: AZA and low-dose GC |
Yes | Median: 39 months |
Remission: 100% within 6 week Relapse: 3 major and 2 minor in 5 patients (21%) at a median of 30 months, treated by redosing with RTX for major relapses and GC increase alone for minor relapses |
AE: 21 SAE: 3 |
| Turner-Stokes et al10
UK |
PCS | Evaluate single dose of RTX for induction treatment of AAV | 19 | Single dose of 375 mg/m2 | GC 8 (42%) were also receiving CYC or MMF |
Yes (<0.005 cells/ml) |
Median: 11.5 months |
Satisfactory BCD in 89% of patients after a median of 13
days; 3-month probability of BCD was 89%. Median time to
CR was 38 days; 3-month probability of CR was
80% Median time to B-cell repopulation 9.2 months and to relapse/re-dose was 27 months. |
Not mentioned |
| McGregor et al11
USA |
PCS | Describe outcomes and adverse events following RTX use in AAV | 120 | 1000 mg on days 0, 14 Or 4 doses of 375 mg/m2/wk |
GC 83% were exposed to CYC 75% receiving MMF 53% receiving AZA |
Yes | Median: 19 months |
RTX resulted in 86% achieving remission and 41% having a subsequent relapse after a median of 19 months (range, 9-29) | AE: not mentioned SAE: not mentioned |
| Pepper et al12
UK & Ireland |
PCS | Early rapid GC withdrawal for induction therapy in patients with severe AAV, using RTX and low-dose CYC | 49 | 1000 mg on days 0, 14 | GC for 2 weeks and CYC Maintenance: from week 12 (first line AZA, Alternatives MMF, MTX, RTX) | Yes | 12 months | Remission: 44/49 (90%) without addition of further GC | AE: 69 SAE: not mentioned |
| Miyazaki et al13
Japan |
PCS | Identify abnormalities in lymphocyte differentiation, analyze its clinical significance, & investigate its effect on using RTX and CYC | 54 | 4 doses of 375 mg/m2/wk | GC | Yes | 6 months | BVAS remission rate: RTX group = 61.8% IV- CYC group = 40.0 [P = .16] No significant differences in the rate of clinical improvement, or relapses between patients receiving RTX and IV-CYC |
AE: RTX: 19 CYC: 14 SAE: not mentioned |
| Smith et al14 | PCS | The use of RTX as therapy to induce remission after relapse in AAV | 188 | 4 doses of 375 mg/m2/wk | GC | Yes | 4 months | 171/188 (90%) achieved remission | AE: 41 SAE: 27 |
| Maintenance regimen | |||||||||
| Guillevin et al15
France |
RCT | RTX vs AZA for remission maintenance in AAV after induction with CYC-based regimen | 115 | 6 months after induction: RTX 500 mg on days 0 and 14 then at months 6, 12, & 18 | Low-dose oral GC | Patient were B-cell depleted on recruitment | 28 months | Major relapse: AZA group: 17 patients (29%) RTX group: 3 patients (5%) HR 6.61 (1.56-27.96; P = .002) |
AE: not mentioned SAE: RTX: 39 AZA: 44 |
| Charles et al16
France |
RCT | Evaluate the efficacy of prolonged RTX therapy vs placebo in preventing AAV relapses after achieving CR | 97 | 500 mg every 6 months (4 doses) |
GC | Yes | 28 months | Relapse-free survival: RTX group: 96% (95% CI, 91%-100%) Placebo group: 74% (63%-88%) in the RTX HR of 7.5 (CI, 1.67-33.7) (P = .008) Major relapse-free survival at month 28 100% (93%-100%) vs 87% (78%-97%) (P = .009) |
AE: not mentioned SAE: RTX: 21 placebo: 18 |
| Induction and maintenance regimen | |||||||||
| Charles et al17
France |
RCT | Compare tailored vs fixed-schedule RTX regimen to maintain remission | 162 | Tailored arm: 500 mg; then further 500 mg doses based on
ANCA and CD19+ count every 3 months Control-arm: 500 mg on days 0 and 14, & at months 6, 12, 18 |
GC | Yes | 28 months | 21 patients suffered 22 relapses: 14/81 (17.3%) in
tailored-arm and 8/81 (9.9%) in fixed-arm
(P = .22). The tailored vs fixed-schedule groups, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) per patient |
AE: not mentioned SAE: Tailored: 37 Control: 53 |
Note. ANCA = antineutrophil cytoplasm antibody; RTX = rituximab; RCT = randomized controlled trial; CYC = cyclophosphamide; CR = complete remission; AAV = ANCA associated vasculitis; wk = week; GC = glucocorticoids; AZA = azathioprine; AE = adverse events; SAE = severe adverse events; PCS = prospective cohort study; MMF = mycophenolate mofetil; BCD = B-cell depletion; CI = confidence interval; IQR = interquartile range; PLEX = plasma exchange; MTX = methotrexate; BVAS = Birmingham vasculitis activity score; HR = hazard ratio.