The most important role of T/S is in preventing Pneumocystis pneumonia, which can occur in 10% of WG patients receiving induction therapy. For patients on MTX, T/S has been safely given at prophylactic doses of trimethoprim 160 mg/sulfamethoxazole 800 mg three times a week or trimethoprim 80 mg/sulfamethoxazole 400 mg daily.
Fulminant Disease
Patients with pulmonary hemorrhage or rapidly progressive glomerulonephritis are often treated with IV methylprednisolone 1 g/day for three days together with CYC 3–4 mg/kg/day for three days, after which time doses are reduced to induction levels. Because there have been no data from standardized trials, this approach must weigh the unknown benefit against increased risk of infection.
In a recent study, 137 patients with rapidly progressive glomerulonephritis due to WG or MPA were treated with CYC and randomized to receive either plasma exchange (PE) or pulse methylprednisolone.15 PE increased the rate of renal recovery compared with methylprednisolone, although patient survival and the rate of severe adverse events were similar in both groups. This trial did not allow conclusions on the effectiveness of combining PE and methylprednisolone or on the impact of PE on other severe manifestations such as pulmonary hemorrhage.
Web Resource:
Patient Fact Sheet
To download the ACR’s patient fact sheet on WG, go to www.rheumatology.org and follow the links to patient education from the Practice Support Menu.
Biologic Therapies
Anti-TNF Therapy: The presence of granulomatous inflammation in WG raised interest in the use of anti–tumor necrosis factor (TNF) agents for the treatment of this disease. In the Wegener’s Granulomatosis Etanercept Trial (WGET), patients received standard induction-maintenance therapy and were randomized to receive etanercept or placebo.16 At the primary endpoint of sustained remission of over six months, there was no difference between etanercept and placebo, demonstrating that etanercept played no beneficial role in the treatment of WG. Investigators observed six malignancies in the etanercept arm; all malignancies had received concurrent CYC during the trial.17 Although this remains a focused experience, these data raise caution about the use of any anti-TNF therapy together with CYC. The divergent efficacy between etanercept, infliximab, and adalimumab in Crohn’s disease has raised the question as to whether other anti-TNF medications may be effective in WG. Until a sufficiently powered trial is performed, the available experience does not support the use of any anti-TNF agent in the routine care of patients with WG.
Rituximab: A promising body of data has emerged with the use of rituximab in WG. Following an initial case report, rituximab was studied in compassionate and open-label studies in combination with glucocorticoids.18,19 This experience found that rituximab was able to induce remission in association with B lymphocyte depletion and had a good safety profile. Although there have been a number of other small series, these data remain too small to draw conclusions regarding the efficacy of rituximab in WG. A randomized, double-blind, placebo-controlled trial is currently underway to compare rituximab to CYC for remission induction of severe active WG. Until data from this trial become available, rituximab should be considered investigational and should not be used in place of standard therapies.