Background/Purpose: Methotrexate has been shown to be effective for both induction (non-severe disease) and maintenance of remission in patients with Granulomatosis with Polyangiitis (GPA) in the context of controlled clinical trials. Limited data are available regarding the long term efficacy of methotrexate in the routine care of patients with GPA. We conducted this study to determine the outcomes of routine methotrexate use in a cohort of patients with GPA.
Methods: Single center retrospective study of patients of GPA treated with methotrexate for either induction or maintenance of remission between January 1997-December 2012. Measured outcomes included time to remission, time to relapse and adverse effects of methotrexate. Remission was defined as Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG) of 0 with prednisone dose < 10 mg/d. Disease relapse was defined as an increase in the BVAS/WG of 1 point or more after having achieved remission. Kaplan Meier estimation with Log-rank test was used for evaluation of the efficacy outcomes.
Results: Seventy-four patients with GPA were treated with methotrexate. Thirty-nine patients (53%) were c-ANCA/PR3 positive, 22 (30%) were p-ANCA/MPO positive and 13 (17%) were ANCA negative. The mean age (standard deviation, SD) at diagnosis was 48.6 (15.3) and 26 (35%) were men. GPA was biopsy proven in 57 patients (77%). At the time of diagnosis, the mean BVAS/WG was 7.0 (SD, 3.9). Of the total cohort, 18 patients (24%) used methotrexate for remission maintenance. The remaining 56 used methotrexate for induction of remission; eleven of these patients (15%) did not achieve remission with methotrexate. From the remaining 45 patients, 35 patients that used methotrexate for remission induction in newly diagnosed non-severe disease achieved remission at a median of 100 days (IQR, 84-153); 10 patients that used methotrexate for remission induction after a relapse were able to achieve remission after a median of 75 days (IQR, 50-114) (p=0.04). Nineteen patients relapsed, 15 (31%) in the induction group and 4 (28%) in the maintenance group (p=0.99). The time from achieving remission to relapse was 589 days (IQR 260-1153) in the induction group versus 781 days (IQR, 93-863) in the maintenance group, p=0.7. The cohort was followed at our institution for a median of 3.5 years (IQR, 1.6-10.3). At the time of conclusion of follow-up, 37 (50%) remained on methotrexate. Methotrexate had to be discontinued in 5 (6.8%) patients due to side effects. Liver toxicity followed by nausea/vomiting were the most commonly experienced adverse events. One patient developed Pneumocystis jirovecii pneumonia while on methotrexate.
Conclusion: In this clinical cohort of GPA patients treated with methotrexate, the time to achieve remission was significantly shorter for patients treated for induction after a relapse as compared to patients treated for initial induction. Time to relapse was not different for patients treated with methotrexate for maintenance therapy as compared to patients treated for induction of remission. Methotrexate is well tolerated long-term, and only a minority of patients had to discontinue methotrexate due to adverse events.
Disclosure:
M. L. Krause,
None;
M. Baqir,
None;
R. Cartin-Ceba,
None;
T. Peikert,
None;
K. Keogh,
None;
U. Specks,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-methotrexate-for-remission-induction-and-maintenance-in-granulomatosis-with-polyangiitis-in-routine-clinical-practice/