SP0005 CASE 1 DISCUSSANT: LONG TERM EFFICACY OF REMISSION-MAINTENANCE REGIMENS FOR AAV
Authors: Loïc Guillevin
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> ANCA-associated vasculitides (AAVs) are a group of diseases with frequent relapses that can sometimes be severe. Treatment comprises an induction-remission phase followed by a maintenance regimen. Induction-remission therapy is effective and now well-established, mainly based on the combination of corticosteroids (CS) and cyclophosphamide or rituximab. For decades, maintenance therapy was compulsory and consisted of azathioprine or methotrexate, combined or not with low-dose CS. That regimen was prescribed for at least 18 months but was sometimes taken for several years. Criteria for stopping treatment have never been codified. Since rituximab has been widely prescribed for induction, the indication for azathioprine maintenance has been challenged because its relapse rate at 18 months (29%) was comparable to that of placebo (32%) given in its stead. However, we considered those relapse rates unacceptably high and have tried to devise a different therapeutic approach to maintenance, with semestrial evaluation of the indication of rituximab infusion over 18 months. MAINRITSAN1-trial results demonstrated the superiority of rituximab to maintain remission with a 5% relapse rate at 28 months vs 29% for azathioprine recipients. The 60-month follow-up of that trial confirmed the superiority of rituximab over azathioprine (37% vs 57%), even though rituximab did not abrogate relapses. Since the publication of those results, it is now clear that AAV remission-maintenance therapy should be rituximab—and not azathioprine or another equally effective immunosuppressant like methotrexate. Maintaining remission should now also be based on other factors predictive of relapse: vasculitis type, ANCA subtype and/or ANCA presence or absence at the end of the induction regimen. Granulomatosis with polyangiitis relapses more frequently than microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis. Relapse rates of the former two are probably linked mainly to ANCA type, anti-PR3 or anti-MPO, with the latter relapsing less frequently. The long-term MAINRITSAN1-trial results identified anti-PR3 presence 1 year after ending induction treatment and/or their persistence were predictor(s) of relapse. We also designed a study comparing fixed-schedule rituximab infusions to re-infusions[JJ1] guided by ANCA titer and/or CD19+ circulating B lymphocytes. Results of that prospective study demonstrated that fewer rituximab infusions should be given but that ANCA titer and the circulating CD19+ B-cell level are not good predictors of relapse. ANCA presence—independently of their titer—is more frequently associated with relapse. The optimal rituximab-administration duration has not yet been established. Our group is now awaiting the imminent results of a prospective trial comparing 4 vs 8 rituximab infusions at 6-month intervals after obtaining remission. <h3>Conclusions:</h3> Major advances have been made in the therapeutic strategy for AAVs. After remission is obtained: 1) AAVs require maintenance therapy, 2) rituximab is superior to immunosuppressants, 3) the presence, persistence and/or reoccurrence of anti-PR3 ANCA predict relapses, 4) the 500-mg rituximab dose/infusion seems well-adapted. The optimal treatment duration remains to be elucidated. Tailoring maintenance therapy is now the main therapeutic objective for AAV management. Future trials will attempt to evaluate very long-term maintenance treatment of AAVs with the goal of eradicating relapses. <h3>Disclosure of Interests:</h3> None declared