recommend a reduced-dose glucocorticoid tapering regimen rather than the standard-dosing taper.
Organ-threatening or life-threatening disease – Organ- or life-threatening features include, but are not limited to, the following (see 'Organ- or life-threatening disease' below): •Active glomerulonephritis •Pulmonary hemorrhage •Cerebral vasculitis •Progressive peripheral or cranial neuropathy •Orbital pseudotumor •Scleritis •Gastrointestinal bleeding due to vasculitis •Cardiac disease due to vasculitis (pericarditis, myocarditis) ●
In a retrospective study of 167 patients with GPA or MPA who were followed for five years, achieving a low disease activity state (defined as a Birmingham Vasculitis Activity Score ≤3 and use of prednisone ≤7.5 mg daily) was associated with more organ damage than prolonged complete remission (Vasculitis Damage Index score 3.7 versus 2.2) [
Defining and characterizing the impact of "partial remission" is further complicated by recognition that some clinical trials in GPA and MPA defined a state of remission as including patients with a single item of nonsevere disease activity .
a patient in whom the systemic symptoms and signs resolve and the urine sediment becomes inactive is considered to be in remission,
induction regimen consisting of glucocorticoids in combination with either rituximab or cyclophosphamide rather than monotherapy with glucocorticoids.
Some authors/editors choose a rituximab-based regimen for the majority of patients, given its comparable efficacy and different side-effect profile compared with cyclophosphamid
Prior to the introduction of cyclophosphamide as a therapy for GPA or MPA, the majority of patients were treated with glucocorticoid monotherapy, but mortality rates with this therapy were high [2,13]. Observational studies found that the combination of cyclophosphamide plus glucocorticoids as induction therapy was associated with more than a fivefold improvement in survival and a lower frequency of relapse
In addition, in the 100 patients with relapsing disease, rituximab was superior to cyclophosphamide in inducing remission (67 versus 42 percent) at six months. The rates of adverse events were similar between the two groups.
Of the 197 patients initially enrolled in RAVE, the 146 patients who achieved complete remission were followed through month 18 . In this trial, rituximab-treated patients received no further therapy, while cyclophosphamide-treated patients were converted to azathioprine immunosuppression within the first six months of treatment.
Although few patients over the age of 75 were included in the two aforementioned trials, rituximab appears to be effective in this patient population.
It remains uncertain whether the ANCA serotype (ie, proteinase 3 [PR3]-ANCA versus myeloperoxidase [MPO]-ANCA positivity) affects the response to the specific induction regimen. A post hoc analysis of the RAVE trial found that patients who were PR3-ANCA positive and received rituximab were more likely to achieve remission at six months compared with those treated with cyclophosphamide and azathioprine (65 versus 48 percent, respectively; odds ratio 2.11, 95% CI 1.04-4.30).
However, in a small series of three patients with ANCA-associated vasculitis and a history of anaphylaxis to rituximab, obinutuzumab (an anti-CD20 antibody) appeared to be efficacious and a reasonable alternative .
Both oral and IV regimens are highly effective. Some clinicians prefer IV cyclophosphamide given the lower cumulative dose associated with this administration and theoretical subsequent lower risk of toxicity.
the CYCLOPS trial (15 mg/kg every two weeks for three doses and then every three weeks for three to six months)
. When using intermittent pulses of cyclophosphamide, some clinicians concomitantly administer mercaptoethane sulfonate (MESNA) to prevent cystitis, although the efficacy of this approach is unproven. A more detailed discussion of dosing, dose adjustments, adverse effects, and the use of MESNA is presented elsewhere.
if the initial dose of prednisone is 60 mg/day, it can be reduced by 50 percent to 30 mg in one to two weeks (table 2). Unless higher doses are required for resistant or relapsing disease, prednisone should be tapered to 5 mg daily or discontinued by four to six months.
ome experts institute plasma exchange immediately upon identification of severe kidney disease (eg, serum creatinine >4.0 mg/dL [354 micromol/L] or need for dialysis) while others first consider the response to initial immunosuppressive therapy
If plasma exchange is used, we suggest seven sessions over two weeks (60 mL/kg at each session).
we suggest that 1 to 2 liters of fresh frozen plasma be substituted for albumin at the end of the procedure to reverse pheresis-induced depletion of coagulation factors.