Thursday 5/10/12

Role of B-Cell Therapy in ANCA associated vasculitis

Ulrich Specks, MD (Mayo Clinic, Rochester, MN)

 

Great lecture today by Dr. Specks, the lead author of the RAVE Trial (more on that later) regarding the use of rituximab (RTX) in ANCA-associate vasculitides, specifically granulomatosis with polyangiitis (GPA; formerly known as Wegener’s granulomatosis).  Most of the talk focused on the RAVE trial, which is what I’ll be discussing with this blog post.  First, it is key to know what the inclusion and exclusion criteria are, so that you can be sure your patient fits the clinical trial data.  Inclusion criteria included (but not limited to):  BVAS > 3.  Exclusion criteria, which are usually considered more important when trying to determine if trial data fit your patient, include (but not limited to):  a) alveolar hemorrhage that required IPPV, b) Cr > 4, c) unresponsiveness to CYC previously, or d) “too severe” disease (though this was not adequately defined during the talk, but presumably means crescentic GN).

 

In the RAVE trial, patients were grouped by whether they had *new* disease or *flare*.  In the former group, RTX and CYC were equally effective in inducing remission.  However, in the latter group, RTX was superior to CYC.  I’d refer you to the original trial to determine what the original induction regimen was prior to the flare, as this would be critically important if the patient were induced with CYC and you wanted to limit further CYC exposure.

 

The RAVE trial also grouped patients by type of ANCA positivity.  We know that PR3-positive ANCA patients are clinically somewhat different than MPO-positive ANCA patients.  Interestingly, the way these patients respond to induction therapy is also different.  PR3-positive patients respond better to RTX than CYC.  MPO-positive patients respond equally well to RTX or CYC.

 

Finally, a brief comparison to the RITUXIVAS trial.  RAVE looked at younger patients, less severe disease, but patients who were newly diagnosed or had flares.  The RITUXIVAS trial lowered the prednisone maintainence dose to 10 mg only, while the RAVE lowered it to 0 mg.  Still, the RITUXIVAS trial showed data similar to the RAVE trial, adding more support for the selective use of RTX.