Background/Purpose: Rituximab (RTX) is used in a wide variety of rheumatic disease. Emerging guidelines suggest measuring immunoglobulins (Ig) at pre-treatment screening and prior to repeat cycles of RTX.  The association between hypogammaglobulinemia and infection post RTX has been evaluated in rheumatoid arthritis (RA) trials; however, there is limited data comparing total IgG levels across different diseases. We aim to compare the rate of hypogammaglobulinemia across RA, ANCA-associated vasculitis (AAV), and connective tissue disease (CTD) patients in a cohort at a tertiary university-based medical center. We hypothesized that baseline clinical and laboratory data will allow for risk prediction of hypogammaglobulinemia and infection rates in these patients.

Methods: Medical records of all RA, AAV, and CTD patients treated with RTX in an academic center from 2002 to 2019 were retrospectively reviewed. Baseline data at initiation of RTX, including clinical diagnosis, demographics, DMARD exposure, glucocorticoid (GC) dose, total serum IgG (normal range 0.7 to 1.6 g/dL) and disease activity were assessed.  We defined GC exposure between the two Ig measurements, as an average daily prednisone dose: high (20mg or more), medium (11-19mg), or low (10mg or less).  Analysis was performed using STATA.  Group comparisons were done using chi square for categorical data and T-test for continuous variables.

Results: We screened 302 patients with rheumatologic conditions who were treated with RTX; of these, 165 patients received RTX for RA, AAV or a CTD. 58 of 165 patients had documented IgG levels pre and post treatment with RTX and 14/58 developed new onset hypogammaglobulinemia post RTX.  Rates of hypogammaglobulinemia were significantly higher in AAV than in CTD patients (42.1% vs. 16.7%, p:0.014), despite similar cumulative exposure to RTX.  The rate of hypogammaglobulinemia post RTX was trending higher in patients with AAV compared to RA (42.1% vs. 23.5%, p:0.24) despite AAV patients having lower cumulative exposure to RTX than RA patients (3.3+/-0.3g vs. 6.3+/-1.9g, p=0.1).  GC exposure was greater in GPA versus RA (p< 0.001) and CTD (p=0.003) patients.  Both RA and CTD patients were more likely to have prior exposure to conventional DMARD (cDMARD) versus AAV patients (p=0.005).  RA patients had a higher likelihood of prior exposure to biologics versus AAV patients (p< 0.001). GPA patients were younger than CTD and RA groups. There was no observed difference in the infection rate among the groups.

Conclusion: AAV patients were more likely to develop hypogammaglobulinemia than RA and CTD patients. We identified high GC exposure as a potential risk factor for hypogammaglobulinemia. Age, cDMARD, and biologic exposure were not associated with increased risk of hypogammaglobulinemia.  Reassuringly, infection rate was not increased in the AAV group, potentially reflecting use of prophylactic antibiotics. Limitations include low utilization of quantitative IgG measurements with repeat cycles of RTX in our center. Additional multicenter studies are needed to determine the true risk of low total IgG levels on rates of clinically significant infections, particularly in patients with AAV and high cumulative GC dose.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-rituximab-associated-hypogammaglobulinemia-rates-in-patients-with-systemic-rheumatologic-conditions/