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Table 4 EGPA Trials

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

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

  1. RCT Randomized Controlled Trial, PLEX Plasma exchange, SAE Serious Adverse Event, AE Adverse Event, GC Glucocorticoids, CYC Cyclophosphamide, NS not significant, AZA Azathioprine, MMT Manual Muscle Testing, ALT Alanine Aminotransferase, LFT Liver function tests, PAN Polyarteritis Nodosa, GPA Granulomatosis with Polyangiitis, MPA Microscopic Polyangiitis