POS1145 LONG TERM SAFETY OUTCOMES AND PREDICTORS OF SERIOUS INFECTIONS AMONG PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH RITUXIMAB: OBSERVATIONS FROM A SINGLE CENTER BIOLOGIC REGISTRY
Authors: A. Jose, A. Gopal, M. Gorijavolu, J. Babu K L, A. Nayak, A. C Das, C. Kavadichanda, M. Mary Thabah, V. S. Negi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab(RTX) is increasingly being employed to treat refractory systemic lupus erythematosus(SLE). Though the drug is effective there is a high risk of adverse events including infections. Most trial data have focused only on short term(&lt;1 year) safety and long term follow-up data is lacking. This study was designed to look at the frequency and predictors of infections in patients with SLE who are on long term follow up. <h3>Objectives:</h3> 1.To assess the long term safety outcomes of Rituximab therapy in SLE 2.Describe the profile of infectious complications following RTX therapy in SLE 3.Determine the predictors of serious infections in patients of SLE treated with Rituximab <h3>Methods:</h3> This was a single-centre retrospective observational study. From the departmental biologic registry, SLE patients who received at least 1 gram of RTX were included with additional data from case record forms. Patients were followed up at 3-6 monthly intervals and the status of SLE, infections and non-infectious adverse events were documented. For those patients who did not have follow up for ≥ 1 year, the last available date of follow-up was considered for this study. Demographic, baseline organ involvement, laboratory data, treatment details were collected. Glucocorticoid exposure was assessed in terms of cumulative steroid (prednisolone) dose, standardized steroid dose (glucocorticoid intake per month of exposure) and number of times the patient received a pulse IV methylprednisolone. Any adverse event occurring during or after the administration of Rituximab induction regimen were recorded. A 'serious adverse event' was defined according to guidelines by International Council on Harmonisation (ICH) 1994. The primary outcome assessed was the occurrence of a serious infection. Secondary outcomes included mortality, time to first serious infection, minor infections and other adverse events. <h3>Results:</h3> A total of 76 SLE patients (median age 29 years, 83% females) were included. The median follow-up duration was 27.0 (10-49) months amounting to 177.33 person-years of follow-up. The baseline data of the cohort are represented in Table 1. Forty five patients (59.2%) had at least one adverse event. Among these, non-infectious events occurred in 4 (5.26%). Infusion reactions occurred 3 (3.94%), one requiring discontinuation of therapy. One patient had worsening of pre-existing pulmonary artery hypertension. There were 43 patients(56.57%) who had infectious events and 16(21.05%) of them were serious resulting in 9.02 infections per 100 person-years of follow-up. Sites involved and organisms implicated are listed in Table 2. There were 8 deaths in the cohort resulting in a mortality rate of 4.5 per 100 person-years of follow-up. All cases except one succumbed to serious infection. Male sex, younger patients, CKD, previous cyclophosphamide use, higher cumulative dose of cyclophosphamide, refractory lupus nephritis, higher SLICC ACR damage index at baseline was associated with serious infections (Table 1). Binary logistic regression revealed younger age and presence of disease related damage to be significant predictors of infection(Table 2). A propensity matched analysis with standard-of-care treatment group revealed higher infection rates in the RTX group. <h3>Conclusion:</h3> Serious infections following RTX is common and result in mortality in SLE. More than 50% of them occur after 1 year of RTX administration. Infections arise from common and rare opportunistic organisms. Juvenile lupus and presence of damage at baseline predispose to infections. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>