ANCA Vasculitis

Question 1

describe the trial design for the Walsh et al PEXIVAS 2020 trial?

Answer 1

among severe active ANCA vasculitis

2x2 factorial design (plasma exchange or no, high vs reduced steroids)

randomized 1:1:1:1
704 total patients, 350 in each arm.

Question 2

describe the inclusion and exclusion criteria for Walsh et al PEXIVAS 2020 trial?

Answer 2

inclusion - 15+, new or relapcsing GPA or MPA, history of positive MPO or PR3 antibioties, kidney involvement w/ eGFR < 50 and active sediment or biopsy OR pulmonary involvement w/ DAH (defined as imaging w/ diffuse infiltrates, absence of secondary cause, 1 of bronch w/ DAH, hemoptysis, unexplained anemia <10, CO2 retention).

exclusion - other vasculitis, antiGBM, HD w/in 21 days, prior rental transplant, recent cyclophosphamide or pred, plasma exchange w/in 3 months

Question 3

describe the immunosuppressive regimen in Walsh et al PEXIVAS 2020 trial

Answer 3

steroids
initial - IV methylpred for 1-3 days for up to 3g in both groups

then went to standard vs reduced dosing - reduce dosing starts taper by week 2 and gets 60% fewer overall. stays on at least 5 mg thru 1 year.

CYC
- given for between 13-26 weeks. 15mg/kg IV CYC x2 weeks for 3 doses, q3 weeks for subsequent. 2mg/kg/day if PO.
no PLEX for 24 hours after IV CYC
transitioned to azathioprine for 1 year

ritux
- 4 doses of 375mg/m2 q5-14 days all within 42 days. no PLEX for 48 hours

Question 4

what was the PLEX schedule in Walsh et al PEXIVAS 2020 trial?

Answer 4

7 treatments within 14 days. recieved 60ml albumin at the same time.

Question 5

what were the primary and secondary outcomes of Walsh et al PEXIVAS 2020 trial?

Answer 5

primary - death from any cause OR ESKD (>12 weeks of RRT or kidney transplant within 1 year

secondary - death, ESKD, sustained remission, infections

Question 6

describe the baseline patient characteristics in Walsh et al PEXIVAS 2020 trial?

Answer 6

60-65 years old, 43% female, 40% PR3, 60% MPO, CRP ~45, Cr 3.2, 70% w/o DAH, 8% w/ severe DAH

50% w/ IV CYC, 35% PO CYC, 15% ritux

Question 7

what were the primary results of Walsh et al PEXIVAS 2020 trial?

Answer 7

plex vs no - 28 vs 31%, no significant

high steroid vs reduced - 29.1% vs 30.3% (noninferior) w/ slightly higher rate of infections in the standard dosing (27% vs 33%)