This is the final report in this series and a continuation from Part 2 of the ANCA Associated Vasculitis take home points. An absolutely wonderful lecture given by Dr. Peter Merkel and I just had to share everything I could.
Despite maintenance therapy, many patients will still relapse. In the CYCAZAREM study (2003), following induction therapy, there were no differences between CYC and AZA for the maintenance of remission. However, a significant number of patients, regardless of treatment, still relapsed. The same findings were found with methotrexate. Mycophenolate is not as good as AZA in maintaining remission so this is used less often.
Although traditional maintenance therapies (MTX, AZA, MMF) are not perfect at maintaining remission, they are better than nothing. In all of the maintenance trials, when the immunosuppressive therapy was stopped the relapse rate significantly increased. This is seen even years later after stopping therapy. Perhaps there is a reason why you haven't stopped the chronic low-dose immunosuppressives in your patients with AAV.
Rituximab is as good as cyclophosphamide for inducing remission. The RAVE study showed equivalence between CYC and AZA vs one course of RTX. Again, as per the previous point, we see a steady increase in relapse rate when immunosuppressives are stopped.
Rituximab is EXCELLENT at maintaining remission. The initial concept for this came from 3 good single-centre studies using variable doses of rituximab from 1 gram q6months to 1 gram q4months. The MAINRITSAN trial (NEJM 2014, Guillevin) was an open-labelled RCT that evaluated this question. Patients in the MAINRITSAN trial were induced with a cyclophosphamide-glucocorticoid regimen then randomized to receive rituximab 500 mg IV q6m vs daily oral azathioprine. The rate of relapse at month 28 was 5% in the rituximab group vs 29% in the azathioprine group.
Some patients require low-dose of prednisone (<10 mg) to prevent minor but annoying symptoms (e.g., arthralgia, ulcers, nasal crusting). These minor symptoms occur even while patients are receiving other immunosuppressants. There is no clear consensus on the dose of prednisone and even the study protocols differ in terms of the long-term maintenance dose of prednisone. However, a meta-analysis comparing trials of no prednisone withdrawal vs later prednisone withdrawal vs early prednisone withdrawal showed increasingly greater relapse rates. The bottom line is low-dose prednisone probably prevents some people from having flares (minor flares). Periodic reduction in prednisone dose can be attempted.