Late‐onset neutropenia following rituximab therapy in rheumatic diseases: Association with B lymphocyte depletion and infections

Abstract

Objective. Late-onset neutropenia following rituximab therapy is a well-recognized side effect in lymphoma patients, but only a few cases of late-onset neutropenia have been reported in patients with autoimmune disorders. The purpose of this study was to define the incidence, clinical features, and some of the underlying mechanisms of late-onset neutropenia in relation to rituximab use in several rheumatic diseases.Methods. We conducted a retrospective analysis of a cohort of 209 consecutive patients with rheumatic diseases who had been treated with rituximab at a university hospital between June 2003 and March 2009.Results. Eleven patients with late-onset neutropenia were identified. The highest incidence was observed in granulomatosis with polyangiitis (Wegener's) and systemic lupus erythematosus patients (23% and 20%, respectively), whereas the incidence in rheumatoid arthritis patients was 3%. The median time to onset of neutropenia was 102 days (range 40-362 days) and coincided with the entire period of B lymphocyte depletion; this depletion was more pronounced in patients with late-onset neutropenia (P ‫؍‬ 0.002) than in a control group of 20 matched patients without late-onset neutropenia. Serum IgM levels decreased during the same time and to a significantly greater amount in patients with late-onset neutropenia than in controls (P ‫؍‬ 0.027). No patient with late-onset neutropenia displayed specific antineutrophil antibodies. Seven patients were hospitalized because of infections (6 with sepsis and 1 with febrile neutropenia) that required intravenous antibiotics. Six were treated with granulocyte colony-stimulating factor.Conclusion. In patients treated with rituximab for rheumatic diseases, late-onset neutropenia is a clinically significant adverse event associated with marked B lymphocyte depletion and severe infections. The incidence of late-onset neutropenia appears to vary with autoimmune disease type.

Is Newer Safer? Adverse Events Associated with First-Line Therapies for ANCA-Associated Vasculitis and Lupus Nephritis

“…One rheumatology case series noted late-onset neutropenia in 11 of 209 (5%) patients after a median 102 (range, 40-362) days from last rituximab treatment, with higher incidences in patients with AAV and lupus (28). The incidence of neutropenia was 6% in RITUXVAS and 5% in the long-term follow-up of the RAVE trial (specified as $grade 2 leukopenia).…”

S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis

“…Ob diese generell mit einer erhöhten Infektionsneigung einhergehen, ist nicht eindeutig geklärt [30]. Blutbildverände-rungen wie Leukopenie, Lymphopenie, Neutropenie und Agranulozytose kön-nen unter immunsuppressiver Therapie auftreten [236]. Leukopenien sind ein unabhängiger Risikofaktor für Mortalität bei AAV [138].…”

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use

“…Data in autoimmune rheumatic diseases are more limited and the optimal management of these patients has not been defined. Data from large cohort studies suggested an incidence of 2.5-3.0% in RA, increased to 20% in AAV (33,34). In most cases neutropaenia recovered promptly but counts <0.5 x10 9 /L were associated with severe infection requiring treatment with intravenous antibiotic and granulocyte-colony stimulating factor (GCSF).…”