Chapter 16 ANCA vasculitis

16.1 Induction

16.1.1 Glucocorticoids & Plasma-exchange

MEPEX (2007): - 3g IV methylprednisolone vs. PLEX (in addition to CYC and pred) in patients with AAV and Cr > 500 mcM. The PLEX group fared better for primary compositive outcome of dialysis-independent survival at 3 months. 1-year survival did not differ between groups. Longer-term follow-up found no difference between groups with respect to composite of mortality and ESRF.

PEXIVAS: - factorial, low- vs. standard-dose glucocorticoids and plasma-exchange vs. no plasma exchange. Median Cr 330; alveolar haemorrhage in 25%. Primary outcome was composite of death and ESRF at 2 yrs. Lower-dose steroids were non-inferior w.r.t. primary outcome are caused fewer serious infections during first year. PLEX had no effect on primary outcome (overall and in pre-specified subgroups including Cr > 500 and lung haemorrhage).

16.1.2 Cyclophosphamide

NORAM (2005): - cyclophosphamide vs. methotrexate for early, mild disease. MTX was non-inferior to CYC at inducing remission by 6 months but lead to higher rates of disease relapse.

CYCLOPS (2009) (with longer-term follow-up data published in 2012): - pulsed IV vs. daily oral cyclophosphamide. IV CYC was as effective as daily oral CYC at inducing remission but was associated with higher rates of disease relapse. Leukopaenia was more common with daily oral CYC. Long-term survival and renal function did not differ between groups.

16.1.3 Rituximab

RITUXIVAS (2010): - rituximab (plus two pulses of IV CYC) vs. CYC in newly-diagnosed AAV. Outcomes at 12 months did not differ between groups.

RAVE (2010): - rituximab vs. cyclophosphamide. RTX was non-inferior to CYC at inducing remission in patients with AAV (first presentation and in relapsing disease).

16.1.4 Other agents

MMF can be used for induction in less severe disease.

Stassen et al. (2007): - MMF in patients in whom CYC was contraindicated.

MYCYC (2019): - MMF vs. IV cyclophosphamide for induction of remission in ANCA vasculitis. MMF was non-inferior at inducing remission by 6 months. Relapse rate was higher in MMF group.

16.2 Maintenance

CYCAZAREM (2003): - azathioprine vs. cyclophosphamide after CYC induction for the maintenance of remission in AAV. Relapse rates did not differ between two groups.

IMPROVE (2010): - MMF vs. aza for maintenance after CYC induction. MMF was less effective at preventing disease relapse.

Sanders et al. (2015): - standard (c. 2 yrs) vs. extended (c. 4 yrs) aza after CYC induction. No difference between groups in disease-free survival at 4 yrs.

MAINRITSAN 1 (2014): - rituximab (500 mg 6-monthly) vs. azathioprine after CYC induction for the maintenance of remission. RTX was better at preventing relapse; adverse events did not differ between groups.

MAINRITSAN 2 (2018): - fixed vs. responsive RTX for maintenance. New and relapsing AAV (n = 160) in complete remission after CYC or RTX induction (tiny numbers MTX). Fixed = 500 mg at 0 and 14 days then 6, 12 ,18 months. Responsive = 500 mg at day 0 then repeated if CD19 count > 0 or ANCA status changed (negative to positive or doubling of ELISA titre or doubling of IF dilution). Follow-up for ~2 yrs (28 months). Responsive group recieved fewer infusions (median 3 vs. 5) without increase in relapse rates.

MAINRITSAN 3 (2020): - short vs. extended-duration RTX for maintenance. RCT in AAV after completing 18 months of RTX maintenance (n = 100). RTX vs. placebo every 6 months for a further 18 months (= 4 infusions). Total relapse rates c. 5 vs. 25 % by 2 yrs; major relapse 0 vs. 13%.

RITAZAREM (not yet published): RTX vs. aza after RTX induction for relapsing disease. Not published yet but results posted online and presented as an abstract. Results from observational induction phase have been published. Significantly fewer relapses with RTX.

16.3 Adjunctive therapies

Stegeman et al. (1996): - co-trimoxazole vs. placebo in GPA. Co-trimoxaozle reduced risk of relapse and also rates of infection. 20% of patients in septrin group discontinued therapy for side-effects.