From: Hallmark trials in ANCA-associated vasculitis (AAV) for the pediatric rheumatologist
Reference, Country | Study Design | Patient Selection | Experiment | Comparators | Primary Outcome | Results | Adverse Events |
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Induction Trials | |||||||
Guillevin et al., 1991, France | RCT | PAN or EGPA | Group A: GC (1 mg/kg/day for 1 month then tapered) and PLEX (12 exchanges in first 2 months) (n = 36) | Group B: GC only (1 mg/kg/day for 1 month then tapered) (n = 42) | Control of disease (Recovery, remission), or death | 78 patients (18 EGPA patients) Primary Outcomes: Complete remission: 27 in group A, 29 in group B Relapse: 10/36 in group A, 8/42 in group B Death: 6 in group A, 9 in group B. No significant difference in 7 year cumulative survival rates | Deaths part of primary outcome |
Guillevin et al., 1995, France | RCT | Severe PAN or EGPA with features of poor prognosis | Additional use of PLEX: GC (15 mg/kg/day IV for 3 days, then PO 1 mg/kg/day for 1 month with tapering) and IV CYC pulse (600 mg/m2 every month for a year) and PLEX (9 exchanges in 3 weeks) (n = 34) | GC (15 mg/kg/day IV for 3 days, then PO 1 mg/kg/day for 1 month with tapering) and IV CYC pulse (600 mg/m2 every month for a year) (n = 28) | Relapse or remission or death | 62 patients (14 EGPA patients) Primary Outcomes: Remission: 16 in no PLEX group, 22 in PLEX group Relapse: 4 (14%) in no PLEX group, 3 (9%) in PLEX group Death: 7 (25%) in no PLEX group, 4 (11.8%) in PLEX group | AEs in PLEX group: pulmonary TB in 3 patients, pneumonia in 3 patients, acute sigmoiditis in 1 patient, and septicemia in 2 patients |
Gayraud et al., 1997, France | RCT | Good prognosis PAN or EGPA | Group A: GC (1 mg/kg/day for 1 month, decreased by 2.5 mg every week until 10 mg/day. At 6 months, decreased by 1 mg/week) and oral CYC (2 mg/kg/day) for 12 months (n = 12) | Group B: GC (1 mg/kg/day for 1 month, decreased by 2.5 mg every week until 10 mg/day. At 6 months, decreased by 1 mg/week) and IV pulse CYC (600 mg/m2 every month for a year) (n = 13) | Complete remission rates | 25 patients (8 EGPA patients) Primary Outcome: Complete remission in 9 (75%) in Group A, 10 (77%) in Group B Secondary Outcomes: Relapses: 2 in each group Failures: 1 in each group | 10 patients in group A experienced AEs, 8 in group B experienced AEs |
Cohen et al., 2007, France | RCT | EGPA patients with features of poor prognosis | Shorter CYC regimen: GC (15 mg/kg/day IV for 3 days, then 1 mg/kg/day oral for 1 month followed by tapering) and 6 IV CYC pulses (600 mg/m2 every 2–4 weeks) (n = 23) | GC (15 mg/kg/day IV for 3 days, then 1 mg/kg/day oral for 1 month followed by tapering) and 12 IV CYC pulses (600 mg/m2 every 2–4 weeks) (n = 25) | Complete remission rates | 48 patients Primary Outcome: Complete Remission in 21 (91%) in 6 pulse group vs 21 (84%) in 12 pulse group (NS) Secondary Outcomes: Relapses:18 (86%) ha a relapse in the 6 pulse group, 13 (62%) had a relapse in the 12 pulse group Deaths: 2 patients died in each group | Similar AE between groups (13 patients in the 12-pulse group compared to 11 patients in the 6-pulse group) |
Ribi et al., 2008, France | RCT | EGPA patients without features of poor prognosis who had treatment failure or relapse on GC alone (could not taper below 20 mg or those who experienced relapse) | AZA (2 mg/kg/day) for 6 months (n = 8) | 6 IV CYC pulses (600 mg/m2 every 2–4 weeks) (n = 10) | Complete remission rates | 72 patients, but 19 patients met inclusion criteria Primary Outcome: 5 (50%) in the CYC group experienced remission, 7 (78%) in the AZA group achieved remission (NS) | CYC AE: Hemorrhagic cystitis (n = 1), Infertility (n = 1) AZA AE: Skin rash (n = 2), elevated LFTs (n = 1) |
Pagnoux et al., 2015, France | Nonblinded, RCT | ≥ 65 years old with new diagnosis of PAN, GPA, MPA, or EGPA | Shorter GC duration and lower CYC doses: GC for 9 months (started at 1 mg/kg/day and tapered) and six 500 mg IV CYC pulses every 2–3 weeks | 26 months of GC (3 additional pulses for consolidation before maintenance for at least 18 months) and 500 mg/m2 IV CYC pulses every 2–3 weeks | Occurrence of ≥ 1 SAE, including deaths from all causes, during the 3 years of follow-up | 104 patients (14 EGPA patients). Primary Outcome: 32 (60%) of the patients in the experimental arm had ≥ 1 SAE versus 40 (78%) of the patients in the conventional arm (p = 0.04). 9 (17%) in the experimental arm and 12 (24%) in the conventional arm died Secondary Outcomes: Remission not achieved in 6 (11%) in experimental arm, 7 (14%) in the conventional arm (p = 0.71) Relapse occurred in 20 (44%) in experimental arm, 41 (29%) in conventional arm | Part of the primary outcome of the study |
Puechal et al., 2017, France | RCT | EGPA, PAN, MPA without features of poor prognosis | AZA (2 mg/kg/day) and GC (1 mg/kg/day for 3 weeks then tapered) | Placebo and GC (1 mg/kg/day for 3 weeks then tapered) | Combined rate of remission induction failures and minor or major relapses at month 24 | 95 patients (51 EGPA patients) Primary Outcome: 22 (48%) in the AZA group and 24 (49%) in the placebo group met end point (NS) Secondary Outcomes: No difference in initial relapse rates, relapses | Similar AE and SAE between groups |
Wechsler et al., 2017, USA | RCT | Relapsing or refractory EGPA who received treatment for 4 weeks and on stable doses of GC | Mepolizumab 300 mg subcutaneous every 4 weeks plus standard care for 52 weeks (n = 68) | Placebo and standard care for 52 weeks (n = 68) | Accrued weeks of remission and proportion of participants in remission at weeks 36 and 48 | 136 patients Primary Outcomes: Accrued weeks of remission: 28% in Mepolizumab and 3% in placebo arm had > 24 weeks in accrued remission (significant) Proportion in remission at week 36 and 48: 32% in Mepolizumab and 3% in placebo group (significant) Secondary Outcomes: Remission failure: 47% failed in Mepolizumab group, 81% failed in placebo group | Similar AE between groups (Mepolizumab: 97%, Placebo: 94%). Serious AEs: Mepolizumab 18%, Placebo: 26% |
Maintenance Trials | |||||||
Koike et al., 2015, Japan | RCT | EGPA patients with chronic residual peripheral neuropathy after disease remission | Group A: IVIG (0.4 g/kg for 5 days) followed by placebo then placebo (n = 8) Group B: Placebo, followed by IVIG (0.4 g/kg for 5 days), then placebo (n = 8) Group C: Placebo, followed by placebo, then IVIG (0.4 g/kg for 5 days) (n = 7) Treatments provided at 2 week intervals | Amount of change in the MMT sum score 2 weeks after IVIG administration | 23 patients MMT change after IVIG: 7.13, significant increase when compared to baseline scores Scores were increased significantly after 4, 6, 8 weeks after observation | AE in 14 patients (61%). Headaches (n = 4) and elevated ALT (n = 3) were most common |