Background:Rituximab (RTX) is an anti-CD20 monoclonal antibody that suppresses B-lymphocytes and may induce hypogammaglobulinemia. Studies have shown that sustained low levels of immunoglobulins (Ig) are associated with significantly increased risks of infections.Objectives:To determine the relationship between the serum Ig levels and risk of infection during (RTX) therapy for rheumatic diseases. We also aimed to identify the most common type of infections and pathogens associated with them.Methods:A multi-centre retrospective observational study of patients with autoimmune diseases treated with RTX between 2009-2019. Serum Ig levels (IgM, IgG and IgA) were measured at baseline and 6-12 months after each cycle and note was made of any hypogammaglobulianemia. Infections, evidenced by a positive microbiology sample, radiograph or requirement of antibiotics and/or hospitalization, were recorded.Results:146 patients were included with a mean age of 61.5 years (standard deviation 13.8). 105 patients (71.9%)) had Rheumatoid Arthritis. 51/146 had had 1or more episodes of infections whilst on Rituximab which required treatment. Of these, 26 (50.9%) had recurrent infections. 33/51 had low immunoglobulins of at least 1 type. After receiving RTX treatment, 14 had low IgG, 29 had low IgM and only 4 had low IgA. 6 patients with low IgG, but 13 patients with low IgM suffered with recurrent infections.There was a statistically significant higher proportion of patients with infection who had low Ig levels compared to those with normal levels, with a p < 0.01 on chi square testing.Lower respiratory tract infections were the commonest infection seen with 28 cases, with most cases (15/28) caused by Haemophilus Influenza. 18 cases of urinary tract infections were seen, with 12/18 being caused by E. Coli. 3 cases of shingles were also seen.Conclusion:Our study shows that an increased risk of infection was associated with hypogammaglobulinemia after rituximab therapy and highlights the importance of monitoring these patients. In our data set, more patients with recurrent infections had low IgM, supporting a need for better understanding of low IgM and its relation to infection. Respiratory tract infections were the most common infection with Haemophilus Influenza being the commonest pathogen. Recent studies have shown an increase in haemophilus influenza infections. Reasons for the increase may include a waning immunity to Haemophilus, changes in the organism and greater numbers of high-risk people- such as in our study. This supports a rationale for extended indication for immunisation against Haemophilus in vulnerable groups of adults and has implications for targeted adult Haemophilus influenzae vaccine development.References:[1]Kridin K, Ahmed AR. Post-rituximab immunoglobulin M (IgM) hypogammaglobulinemia. Autoimmunity Reviews. 2020 Jan 6:102466.[2]Barmettler S, Ong MS, Farmer JR, Choi H, Walter J. Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia.JAMA Netw Open. 2018;1(7):e184169. Published 2018 Nov 2.[3]Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections.Clin Lymphoma Myeloma Leuk. 2013;13(2):106–111.[4]Nix EB, Hawdon N, Gravelle S, et al. Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era.Clin Vaccine Immunol. 2012;19(5):766–771.Disclosure of Interests:None declared
Genetic Sequence of Drug-Resistant Haemophilus influenza Isolated from Respiratory Tract Infections
