Serious Infectious Events and Immunoglobulin Replacement Therapy in Patients With Autoimmune Disease Receiving Rituximab: A Retrospective Cohort Study.

BACKGROUND: Rituximab (RTX) is widely administered to patients with autoimmune disease (AID). This study aimed to estimate the incidence of serious infectious events (SIEs) after RTX initiation in patients with AID. We also described the characteristics and risk factors of SIEs, and immunoglobulin replacement therapy (IgRT) strategies. METHODS: Patients treated between 2005 and 2016 were included in this retrospective monocentric cohort study. An RTX course was defined as the complete RTX treatment regimen received by a given patient for AID. SIEs and IgRT were right-censored at 24 months after RTX initiation. RESULTS: Two hundred twenty-one patients were included (corresponding to 276 RTX courses). Reasons for RTX initiation included connective tissue disease (38%), systemic vasculitis (36%), and autoimmune cytopenia (22%). The 1- and 2-year incidences of SIEs were 17.3 (95% confidence interval [CI], 12.0-22.5) and 11.3 (95% CI, 8.1-14.5) per 100 person-years, respectively. Forty-seven SIEs were observed, mostly comprising pneumonias (45%) and bacteremias (21%). When documented, the microorganisms were bacterial (55%) and fungal (12%). Identified risk factors of SIEs were age, history of diabetes, history of cancer, concomitant steroid treatment, and low CD4 lymphocyte count at RTX initiation. IgRT was started in 22 RTX courses (8%). CONCLUSIONS: In patients with AID treated with RTX, the 1- and 2-year incidence of SIE was 17.3 and 11.3 per 100 person-years, respectively. Reports of SIE characteristics, risk factors, and IgRT strategies highlight the need for an appropriate and individualized assessment prior to and following RTX to prevent SIEs, particularly in patients with comorbidities.

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab.

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case-control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6±18.8 vs 48.8±16.7; p=0.0091), suffered most frequently of diabetes mellitus (33.3% vs 5.3%, p=0.015), had a lower CD19 count (1.0±1.2/mm3 vs 3.9±7.2/mm3) and had most frequently a prednisone dose>15 mg/day (91.7% vs 47.7%) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (OR=0.87, 95%CI=0.77-0.99, p=0.03), lower CD19 count (OR=0.85, 95%CI=0.73-1.00) and creatinine clearance≤45 ml/min (OR=7.78, 95%CI=1.36-44.38, p=0.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (OR=0.11, 95%CI=0.03-0.41, p=0.0009). Concomitant treatment with prednisone at a dose>15 mg/day significantly increased the SIE risk (OR=8.07, 95%CI=1.94-33.59, p=0.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.