Rituximab for remission induction in elderly patients with ANCA-associated vasculitis

https://doi.org/10.1016/j.semarthrit.2015.02.005Get rights and content

Abstract

Objectives

Advancing age is a risk factor for treatment-related side effects and mortality in AAV patients treated with cyclophosphamide (CYC) and glucocorticoids (GC) for remission induction. The efficacy and safety of rituximab (RTX) in elderly AAV patients has not been well described.

Methods

We performed a single center retrospective review of 31 consecutive AAV patients aged 60 or more at the time of RTX use for remission induction. All patients received RTX with GC for remission induction. Four patients received concomitant CYC for a mean duration of 52 days. We evaluated clinical and laboratory variables at diagnosis, rates of complete remission defined as Birmingham Vasculitis Activity Score/Wegener’s Granulomatosis (BVAS/WG) = 0 and patient survival, renal survival, infections requiring hospitalization, and vasculitis relapse 24 months following RTX use.

Results

Of the 31 patients, 77% were Caucasian, 68% female, mean age was 71 ± 6 years, 58% were MPO ANCA positive, and 42% had relapsing disease. The mean BVAS/WG score entry was 4.4 ± 1.5, 71% had glomerulonephritis (GN) and 10% had alveolar hemorrhage. The mean baseline e-GFR was 40 ± 28 ml/min/1.73 m2. Thirty patients achieved remission with a mean time to remission of 57 ± 27 days. The single patient with refractory vasculitis responded to CYC. The mean prednisone dose at 6 months was 5.6 ± 4 mg. Remission maintenance therapy was started within 12 months of RTX induction in 6 patients (4 with RTX, 1 with azathioprine, and 1 with mycophenolate mofetil). One patient suffered a limited relapse 10 months post RTX use. Among the 22 patients with GN at baseline, 1 developed ESRD. One-year patient survival among 25 patients with at least 1 year of follow-up was 100%. There were no episodes of infusion reaction or leukopenia. There were 3 episodes of bacterial pneumonia, 1 episode of candida pneumonia, and 1 episode of disseminated cutaneous zoster.

Conclusions

This study demonstrates that rituximab is effective for remission induction in elderly patients with AAV. Furthermore, we observed a high incidence of infectious complications. Our experience was limited by its retrospective design, and further studies are needed to evaluate the efficacy and safety of RTX in elderly AAV patients.

Introduction

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are systemic small vessel vasculitis and categorized as granulomatosis with polyangiitis (Wegener’s), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome), and renal-limited vasculitis. The routine use of cyclophosphamide dramatically changed the prognosis associated with AAV, transforming many of these previously fatal diseases into chronic illnesses [1]. However, the cost of remission induction with cyclophosphamide is substantial with 42% of patients experiencing treatment-related side effects [2] with older age and renal dysfunction being important predictors of treatment-related adverse effects [3], [4]. Strategies minimizing or eliminating use of cyclophosphamide for remission induction have been the subject of randomized vasculitis trials in the last decade. Rituximab, a chimeric mAb that binds to the CD20, was approved for remission induction in AAV in 2011 based on RAVE and RITUXVAS trials [5], [6]. The mean age of patients in the rituximab arm of RAVE trial was 54 years and the median age of patients in the RITUXVAS study was 68 years with a range of 56–75 years. The efficacy and safety of rituximab for remission induction for AAV in elderly patients has not been well studied. We report our experience with using remission induction for AAV in elderly patients defined as age greater than or equal to 60 years at a single university medical center.

Section snippets

Study population

Potential patients for this retrospective study were identified from a vasculitis clinic database for the study period 2005–2014. To be included in the study, individuals had to be 60 years or older at the time of rituximab infusion, have a clinical diagnosis of GPA or MPA and received rituximab for remission induction. This study protocol was approved by the Office of Human Subjects Research and Institutional Review Board.

Acquisition of clinical and laboratory data

Patient demographics, clinical features at the time of diagnosis or

Results

The baseline characteristics of the 31 patients who met the inclusion criteria for this study are presented in Table 1. The mean (SD) age at the time of rituximab infusion among the entire cohort was 71 (6) years (range: 60–83 years). Majority of patients (77%) were Caucasian and female gender (68%). Eighteen patients had a new diagnosis of AAV and the remainder had relapsing disease. Nineteen patients in the cohort had a diagnosis of GPA and 12 patients had a diagnosis of MPA. The mean (SD)

Discussion

This retrospective single center study demonstrates that rituximab is effective for remission induction in elderly patient with AAV. The data also demonstrates that infectious complications are common in this age group.

ANCA-associated vasculitis (AAV) are predominantly diseases of older patients with a peak age of 65–74 years [7]. Elderly patients with AAV are predominantly MPO–ANCA positive compared to PR3 ANCA. AAV in elderly [8], [9], [10], [11] frequently involves the kidney [12]. AAV

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