Objective: To examine the long-term efficacy of low-dose intravenous methotrexate (MTX) with and without concomitant glucocorticoids (GC) for remission maintenance in patients with generalized Wegener's granulomatosis (WG) in an open-label, prospective, standardized trial.
Methods: After induction of remission by cyclophosphamide and GC, 71 patients (41 males, 30 female) with initially generalized WG received low-dose methotrexate at 0.3 mg/kg body weight once weekly. At study-start 55 of 71 (77.5%) patients were on low-dose GC (mean 5.9 mg/day) which was tapered during the study. All patients underwent interdisciplinary staging at 3-month (and later at 6-month) intervals to assess disease activity and extent as well as side effects. End points were the first relapse or the end of study (January 2001).
Results: Within a mean followup period of 25.2 months, 26 patients (36.6%) experienced a relapse after a mean of 19.4 months. Seventeen (65.4%) of these 26 patients had terminated GC therapy at the time of relapse. There was no difference in relapse rates among patients with and without concomitant GC at study start. Relapses occurred mainly in the initially involved organ systems, preferentially in the ear, nose and throat tract in 18 of 26 patients and the kidney in 16 of 26 patients. One renal relapse presented as rapid, progressive glomerulonephritis with lethal outcome. Further, 14 relapses were accompanied by a significant rise in creatinine values. In 15/26 patients the relapse was paralleled or preceded by a significant rise of antineutrophil cytoplasmic antibody titer. Two patients ceased MTX prematurely because of persistent leukopenia.
Conclusion: Weekly MTX is a well tolerated therapy for long-term maintenance of remission. However, one-third of the patients relapsed during ongoing MTX treatment, irrespective of whether they were still receiving GC. Because more than half of the relapses affected the kidney, close monitoring is indispensable.