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OBJECTIVE Late-onset neutropenia (LON) is an underrecognized complication of rituximab treatment. We undertook this study to describe its incidence, risk factors, clinical features, management, and recurrence. METHODS We conducted a single-center retrospective cohort study of 738 adult patients with autoimmune disease who were treated with rituximab to induce continuous B cell depletion. The primary outcome measure was LON, defined as an unexplained absolute neutrophil count of

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a small vessel necrotizing vasculitis with a predilection for the respiratory tract and kidneys.1,2 Prompt initiation of remission induction immunosuppression is paramount to prevent irreversible organ damage.3 Standard initial therapy for severe AAV consists of cyclophosphamide or rituximab in combination with high-dose glucocorticoids.4,5 In cases of severe pulmonary hemorrhage or rapidly progressive glomerulonephritis, plasma exchange is often added to facilitate rapid removal of ANCA.6 Improved understanding of disease pathogenesis has provided the rationale for targeting the complement pathway in AAV.7 In particular, the anaphylatoxin complement component 5a (C5a) has been identified as a key pathogenic mediator of AAV because of its ability to prime and recruit neutrophils.8 Inhibitors of C5a and the C5a receptor are being evaluated in randomized trials, but are not currently available for clinical use.9 Here, we report the use of eculizumab, a monoclonal antibody against C5, in 2 cases of aggressive AAV with the intention of rapidly inducing remission by inhibiting C5a generation. In both patients, religious beliefs prohibiting the receipt of blood products precluded the use of plasma exchange and cyclophosphamide.

Background Consequences of long-term B cell depletion with rituximab are not well understood. We describe inflammatory vaginitis as a potential side effect of long-term rituximab treatment, distinct from previously described vulvovaginal pyoderma gangrenosum. Methods We performed a retrospective analysis of women treated with rituximab for more than 1 year to determine the prevalence and clinical characteristics of vaginitis cases. We conducted a case–control analysis with up to 3 controls for each vaginitis case. Results We identified sixteen inflammatory vaginitis cases. Women with vaginitis were age 23–68 (median 42), primarily being treated for ANCA-associated vasculitis (11/16; 69%). Most reported copious vaginal discharge (100%) and pain with sex (75%). All women with return of circulating B-cells to > 10 cells/mL had complete (5/9) or significant (4/9) improvement in symptoms. In case–control analysis there was no significant difference in length of B-cell depletion, immune parameters, creatinine levels, and history of neutropenia. Conclusion Inflammatory vaginitis is a potential side effect of prolonged continuous B cell depletion with rituximab. More studies are needed to characterize the incidence and etiology of vaginitis among women on long term rituximab therapy and establish a causal relationship.

Background Patients with frequently relapsing (FR), steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome are a therapeutic challenge with limited treatment options. Here, we retrospectively analyze the efficacy and safety of rituximab-induced continuous B-cell depletion in these populations. Methods Patients were included if they were at least 18 years of age and had FR, SD or SR minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) and were treated with a strategy of continuous B-cell depletion. Partial remission (PR) was defined as a urinary protein:creatinine ratio (UPCR) of ≤3.5 g/g and a 50% reduction in the UPCR from baseline. Complete remission (CR) was defined as a UPCR ≤0.3 g/g. Results We identified 20 patients with MCD (n = 13) or FSGS (n = 7) who fulfilled the inclusion criteria. All patients had either SD (n = 12), SR (n = 7) or FR (n = 1) disease. Patients received a median of nine rituximab doses [interquartile range (IQR) 7.5, 11] and were treated for a median time of 28 months (IQR 23, 41). Prednisone was weaned from a median of 60 mg daily (IQR 40, 60) at rituximab initiation to 4.5 mg daily (IQR 0, 5.5) by 12 months. All patients achieved PR. CR occurred in 11 of 13 patients with FR or SD disease, but only 1 of 7 patients with SR disease (logrank P = 0.01). Four relapses occurred, all in patients with SR disease. Three serious infections occurred over 70.3 patient-years. Conclusion Continuous B-cell depletion is a therapeutic option in the management of complicated nephrotic syndrome. Additional studies are needed to clarify the utility of this strategy.