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

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 ± 28ml/min/1.73m(2). 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 ± 4mg. 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.

BK virus replication in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: BK virus (BKV) is an important cause of renal dysfunction in kidney transplant (KTX) recipients. Immunosuppression intensity is a major risk factor for BKV replication in these patients. The prevalence of BKV replication in immunosuppressed patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) without transplant is not known. METHODS: Consecutive patients (n = 37) with a diagnosis of GPA (n = 25) or MPA (n = 12) without history of KTX were evaluated for plasma BKV replication by quantitative PCR (group A). Descriptive data were collected. BKV replication in this nontransplant immunosuppressed vasculitis cohort was compared with a historical cohort of vasculitis KTX recipients (group B). RESULTS: Group A patients had mean disease duration of 75 months. Mean age was 57 years and 54% were female. Mean time from vasculitis onset to BKV testing was 36 months, and 19/37 patients were tested within 24 months of induction therapy. At the time of BKV testing, 73% were on prednisone (P) with azathioprine, mycophenolate mofetil (MMF), methotrexate or leflunomide. None of the nontransplanted vasculitis patients had detectable plasma BKV. Among 35 patients in group B, 16 were tested for BKV; 5/16 (31%) had detectable virus in plasma at a mean of 6 months after TX (p = 0.002). Most (94%) were on maintenance therapy with MMF, P and tacrolimus. CONCLUSION: Immunosuppressed patients with GPA/MPA without KTX had no evidence of plasma BKV. However, BKV was common in GPA/MPA patients after KTX, suggesting that replication may be related to differences in immunosuppression, alloimmune activation or differences in host defense mechanisms.

OARSI-OMERACT initiative: defining thresholds for symptomatic severity and structural changes in disease modifying osteoarthritis drug (DMOAD) clinical trials.

OBJECTIVE: Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs. DESIGN: Post hoc analysis of summary data from the placebo arm of eight DMOAD RCTs. RESULTS: Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22%) and 132 (51%) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5 mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n = 163, 12%) in the least stringent scenario (pain + function ≥80 at ≥2 visits); with few patients (n = 129, 2%) in the most stringent scenario (pain + function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50% difference between groups. CONCLUSIONS: The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued.