Background/Purpose:

Disease remission can be successfully achieved in the majority of patients (pts) with Granulomatosis with polyangiitis (Wegener’s) (GPA).  After remission (rem) is achieved continued treatment with immunosuppressive agents is used to maintain rem.  There is limited data on long term outcomes for pts continuing maintenance therapy beyond 18 months (mo).  The aim of this study was to determine rem maintenance outcomes in pts treated long term (>18 mo) vs. short term (≤18 mo).  The primary outcome was relapse rate. 

Methods:

A retrospective chart review was performed of pts with GPA from a single Vasculitis Center from 1992 to 2010.  Inclusion criteria: 1)1990 ACR criteria for GPA, 2) induction therapy provided with daily cyclophosphamide (CYC) or weekly methotrexate (MTX); 3) rem achieved; 4) maintenance therapy initiated immediately following discontinuation of induction therapy; 5) maintenance therapy with either MTX or azathioprine (AZA); 6) duration of remission ≥18 mon; 7) chronologic documentation of rem and relapse.  Rem was defined as a BVAS/WG score of 0 and relapse was defined as a score that changed from 0 to ≥ 1 following a period of rem.

Results:

157 pts were included out of 797 screened.  Median age at diagnosis was 46.  Follow-up ranged from 18 mo to 16.8 years(yr) (mean 3.1 yr).  Induction therapy with CYC was used for severe disease (78% cases) and MTX (22% cases) for mild to moderate disease.  Mean starting doses of maintenance medications were prednisone (pred) 19 mg/d, MTX 16.5mg/wk and AZA 112mg/d.  There was no difference between groups in regards to initial organ manifestations, pred dose at rem, maintenance drug used or pulse dose methylprednisolone (MP) at diagnosis.  When duration of treatment was compared using a univariate model the long term group showed a 29% reduction in hazard ratio for relapse (HR0.71[95%CI 0.43,1.18],p=0.18).  Treatment for > 36 mo showed 66% reduction in hazard ratio for relapse (HR0.34[95%CI0.15,0.76],p=0.008).  When length of treatment was considered as a continuous factor, longer courses had an inverse relationship with the risk of relapse (HR0.77 [95%CI 0.65, 0.92]; p= 0.003).  After adjusting for pred dose, length of maintenance therapy continued to show a significant inverse relationship with risk of relapse (HR0.58 [95%CI 0.4, 0.83]; p=0.003).  Univariate analysis revealed no association with risk of relapse and BVAS at diagnosis, ANCA status or pulse MP.  When relapse characteristics were compared between groups there was no difference in severity of relapse as measured by BVAS/WG, but a higher rate of relapse with peripheral neuropathy (15%vs1.43%, p=0.033) occurred in the short term group.  Relapses in the long-term group occurred in 88.9% after stopping therapy.  Of pts on therapy at relapse 52% were on < 15mg/wk MTX and 75% on ≤ 50mg/d AZA.  No differences between the two groups in overall adverse events or GPA related morbidity.

Conclusion:

Our data demonstrate that pts receiving long term maintenance therapy have fewer relapses and have a similar adverse events profile as pts treated for < 18 mos.  Discontinuation and low doses of maintenance therapy are associated with a high relapse rate.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/outcomes-in-patients-with-granulomatosis-with-polyangiitis-wegeners-treated-with-short-vs-long-term-maintenance-therapy/