The Recommendations for the Management   of ANCA-Associated Vasculitis (Part 3)


We continue our discussion on this topic by starting off with the subject matter on remission-induction of new-onset organ-threatening or  life threatening antibody (ANCA)-associated vasculitis (AAV).

Experts recommend treatment with a combination of glucocorticoids and either cyclophosphamide or rituximab.

Since the 1970s, therapy using a combination of glucocorticoids (1 mg/kg/day—maximum daily dose 80 mg) with cyclophosphamide (2 mg/kg/day—maximum 200 mg/day) has been practiced for remission induction in AAV. 

Due to concerns about cumulative cyclophosphamide dosage, pulsed intravenous regimens were taken into consideration and tested, the largest study being the Cyclops trial, which is a randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis.

This trial was crafted following a meta-analysis of three studies involving 143 patients which concluded that pulsed cyclophosphamide was  likely to lead towards remission and was associated with fewer side effects than oral cyclophosphamide. 

Long-term follow-up study of the Cyclops cohort shows that while the proportion of participants with at least one relapse was higher compared to patients given with pulsed cyclophosphamide, there were no differences in survival, renal function at the end of the study.

However, pulsed regimens are being favored because of the reduced total dose of cyclophosphamide and lowered risk of complications related to the bladder’s health.

The level of evidence for cyclophosphamide use in  eosinophilic granulomatosis with polyangiitis (EGPA) is lower than for granulomatosis with polyangiitis (GPA)/ microscopic polyangitis (MPA) as no randomised controlled trials (RCTs) for the treatment of EGPA have been publicized before. 

One study compares cyclophosphamide doses: cyclophosphamide (0.6 mg/m2) was initially used every 2 weeks for a month then once every four weeks.

The intervention arm was given six pulses in total, while the control arm received 12 pulses.

Complete remission was achieved in both groups at a similar rate.

As this developed, therapy should be routinely administered with cyclophosphamide given intravenously.

The metabolites of Cyclophosphamide are toxic to the urothelium and may cause hemorrhagic cystitis in the short term and malignancy if exposed in the long term. 

The patients should be encouraged to drink plenty of fluids on the day of the treatment as a measure to dilute the metabolites in the urine. 

Patients receiving pulse cyclophosphamide may also be given oral or intravenous 2-mercaptoethanesulfonate sodium (MESNA) which binds to acrolein, a toxic metabolite of cyclophosphamide, rendering it non-toxic.

MESNA also slows down the degradation of 4-hydroxymetabolites, further reducing the toxic acrolein in the urine. 

MESNA may be helpful in patients who are getting continuous oral cyclophosphamide.

Monitoring of patients receiving cyclophosphamide should follow standard protocols. 

The discontinuation of the administration or dose changes of cyclophosphamide may be needed if acute leucopenia exists or a gradual fall over time. 

If there is a stable leucopenia, the course of action may include maintenance of the immunosuppression with strict blood monitoring.