AB0082 RITUXIMAB THERAPY AND SARS-CoV-2 INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Rituximab, a monoclonal antibody targeting anti-CD 20 contributes to B cell depletion resulting in an increased risk of infections. The rate of serious infections varied from 9.8/100 person –years and during the covid pandemic the use of Rituximab was reported to cause more severe SARS –CoV-2 infections and the treatment can cause blunting of the COVID vaccination response. Objectives: A retrospective observational study was conducted to see if Rituximab was associated with an increased incidence of COVID-19 infection and to assess the impact of hypogammaglobulinemia in the Rituximab treated patients. Methods: We reviewed the hospital and GP health records and identified patients who developed COVID infections while receiving rituximab infusions. We looked at the correlation between immunoglobulin levels and COVID infections. The ranges of immunoglobulin used at the hospital were IgG 2.6-5.9, IgM 0.05-0.35, and IgA 0.12-0.79. Results: A total of 85 patients were identified for this study and, 8 patients (9%) were found to have COVID infection following their rituximab infusion. Of them 3 were females and 5 were males with age ranging from 25 to 80 years. Apart from one patient with COPD there was no significant risk factors noted in the COVID positive group. Only two patients were taking oral steroids long term. There was one documented death due to covid in this group. Of the 8 COVID positive patients, 3 patients had normal Immunoglobulins and the rituximab treatment was discontinued post COVID. All of them made good clinical recovery. The remaining 5 patients with low immunoglobulin levels, 2 patients (case 1 and 5) with mildly low IgM levels and steroids (prednisolone 5mg) developed profound pan-hypogammaglobulinemia following COVID infection. These patients subsequently presented months later with recurrent respiratory infections with positive viral PCR identified in the bronchial aspirates. One patient (case 5) improved following the discontinuation of rituximab while the other (case2) had to be treated with IVIg followed by complete resolution of chest symptoms. Among the rest of the 3 patients, 2 patients (case2 and 4) with recurrent COVID infections were found to have low IgG and IgM and the discontinuation of Rituximab improved the symptoms and finally one patient (Case3) with a pre-existing low IgM was found to have a further reduction in the IgM post-COVID, however, did not develop recurrent COVID infections. The IgG levels were normal in this case. Low IgG levels and prior steroid therapy correlated with the severity more than IgM levels. Conclusion: In our cohort, Rituximab use was not found to be associated with an increased incidence of COVID-19 infections2. However, it was noted that patients on Rituximab who develop COVID are at a greater risk of recurrent and severe COVID-19 infections due pan-hypogammaglobulinemia which can develop during the Rituximab therapy or soon after the initial COVID infection. Some RA patients with profound hypogammaglobulinemia would benefit from IVIg therapy to reduce the severity and to prevent the recurrence COVID infections. the immunoglobulin levels should be monitored during the treatment and soon after COVID infection to identify at risk patients. REFERENCES: 1 O'Bryan C, Espinosa R, Chittivelu S. Hypogammaglobulinemia following COVID-19 infection in a patient on maintenance rituximab. SAGE Open Med Case Rep. 2021 Dec 15; 9:2050313X211065791. 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 Nov 2;1(7): e184169. Acknowledgements: Dr Makkuni Consultant rheumatologist. Disclosure of Interests: None declared.