Mycophenolate Mofetil in Anti-Neutrophil Cytoplasm Antibodies-Associated Systemic Vasculitis

Abstract

Background: Mycophenolate mofetil (MMF) is an immune suppressive initially introduced for the prevention of solid organ allograft rejection that is increasingly used in autoimmune conditions, including vasculitis. Methods: This retrospective study evaluated the efficacy and tolerability of MMF in 51 sequential patients with anti-neutrophil cytoplasm antibodies-associated systemic vasculitis (AASV) treated in a single centre between 2001 and 2004. Results: The mean age was 54 years and median disease duration was 36 months. A mean of 3.5 systems were involved and the previous median exposure to cyclophosphamide was 9 g. MMF was administered either as remission maintenance therapy (29/51, 56.9%) or as treatment for active disease (22/51, 43.1%). The mean duration of MMF therapy was 20 months and the mean MMF dose during the first year was 1.6 g/day. 14/29 (48.3%) of those receiving MMF for remission maintenance therapy eventually relapsed with a mean time to relapse of 14 months. Of those receiving MMF for relapsing disease, 3 failed to respond to therapy while the rest achieved remission by 3.9 months. However, 9 of these subsequently flared; mean time to disease flare was also 14 months. MMF was withdrawn in 28 patients (54.9%) because of treatment inefficacy in 21, severe adverse events in 5 and intolerance in 2. Of the 51 treated, 36 (70.6%) experienced at least 1 side effect, namely infections in 24, gastrointestinal side effects in 12 and psychological events in 6 patients. Conclusions: We have observed varying efficacy of MMF in AASV, with over 50% of patients with relapsing disease achieving remission and marked falls in concomitant steroid doses. However, longer follow-up indicates a subsequent relapse rate of over 50% that may be associated with low MMF dosing.

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

“…The overall response to rituximab in this patient series was superior to that seen with alternative therapies in similar cohorts of patients with refractory vasculitis. In a retrospective series of patients treated with MMF, a reduction in disease activity occurred in 86% (19 of 22); however, few achieved complete remission, and 47% experienced a relapse by 14 months, which required other therapies (25). In a placebo-controlled trial, 82% of patients (14 of 17) responded to IVIG therapy; however, the response was not maintained beyond 3 months (26).…”

Mycophenolic acid in Rheumatology: mechanisms of action and severe adverse events

“…II) (14,(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70). Thanks to its efficacy against kidney transplant rejection and its nephroprotective properties, studies mainly focused on lupus nephritis (LN) as both induction (53-57) and maintenance (14) therapy, and on ANCA-positive vasculitides (59)(60)(61)(62). Moreover, the antifibrotic role of MPA, added to its actions in favor of endothelial protection and against experimental pulmonary hypertension, encouraged studies on systemic sclerosis (SSc) (63)(64)(65).…”

“…Critical issues concerning treatment outcomes are the daily dose administrated and the drug concentration achieved in vivo. Low MMF-dosing could have been responsible for the high rate of relapse, mainly experienced in vasculitis patients (60)(61)(62); also in LN management a slower rate of MMF tapering was soon adopted (54). Whereas MMF 2 g/day was found to be comparable to CTX in LN induction therapy (53-55), MMF 3 g/day seemed to be even superior to CTX (56).…”

Granulomatosis with polyangiitis – therapeutic challenge

“…Varying efficacy of MMF in ANCA-associated systemic vasculitides was observed, with over 50% of patients with relapsing disease achieving remission and marked falls in concomitant steroid doses. However, longer follow-up indicated a subsequent relapse rate of over 50% that may be associated with low MMF dosing [19]. In patients with ANCA-associated systemic vasculitides and renal involvement, MMF seems to be an effective and well-tolerated option in sustaining short-and medium-term remission [20].…”