AB0215 COMPARISON BETWEEN RITUXIMAB ORIGINATOR THERAPY AND ITS BIOSIMILAR IN THE INCIDENCE OF LATE-ONSET NEUTROPENIA IN ADULT PATIENTS WITH RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE DISEASES
Authors: M. M. Ahmad, E. Mcrorie
Journal: Annals of the Rheumatic Diseases (2021)

Background: Late-onset neutropenia (LON) occurs when the absolute neutrophil count drops below 1.5 × 10(9)/L four weeks after Rituximab infusion. 1 It is a condition recognised more in haematological malignancy patients treated with Rituximab with a reported prevalence of 8% or higher. 2 LON was reported in 6.5% of rheumatological patients 1 , while a French registry found a prevalence of 1.3% in rheumatoid arthritis patients. 3 Almost all patients receiving Rituximab originator therapy at our Rheumatology department were switched to its biosimilar starting from November 2017. Our haematology team observed LON cases in their patients after this period. Objectives: We wanted to establish whether there is increased LON occurrence with the biosimilar than the originator therapy, requiring specific monitoring. Methods: This is a cross-sectional retrospective review of 12 months period before and after switching to the biosimilar of all patients who received Rituximab for the first time. We reviewed the patients’ blood monitoring for up to 12 months after receiving Rituximab. We used a proforma to collect the age, sex, diagnosis, date of the first infusion, use of other DMARDs, LON occurrence within 12 months after the infusion and neutropenia within the 12 months before it in addition to the frequency of the blood monitoring after the infusion. Results: For the originator, between 1/1/2016 and 31/12/2016, 142 patients received Rituximab, 47 (33.09%) of them were given the treatment for the first time. Their median age was 62 years, 28 (59.5%) were females. The most common diagnosis was rheumatoid arthritis 38 (80.8%), and 35 (74.4%) patients were on other disease-modifying agents (DMARDs). Two patients (4.2%) developed LON. In both patients, this occurred during admission for septic arthritis whilst on antibiotics, and both had Grade 2: ≥1,000– &lt; 1,500/mm3 neutropenia. For the Biosimilar cohort, between 1/4/2019 and 31/3/2020, 161 patients received Rituximab, 36 (22.3%) of them were given the treatment for the first time. Their median age was 59 years, 27 (75%) of them were females. The most common diagnosis was rheumatoid arthritis 25 (69.4%), and 26 (72.2%) were on other DMARDs. One patient (2.77%) developed grade 2 LON one month after Rituximab. Another patient with known autoimmune neutropenia was excluded. In all the Three patients with LON in both groups, neutrophil count recovered in less than a month, and they had normal IgG before the infusion. The frequency of blood monitoring after Rituximab infusion was done 1-3 monthly in 32 (68%) patients and 23 (63.8%) patients in the originator and biosimilar groups, respectively. Four (8.5%) patients and three (8.3%) patients in the originator and biosimilar groups respectively had a frequency of blood monitoring done less than six-monthly. Conclusion: In our patients’ cohort, LON incidence following switching to the Rituximab biosimilar was not higher than the originator therapy. References: [1]Monaco, W. E., Jones, J. D. &amp; Rigby, W. F. C. Rituximab associated late-onset neutropenia-a rheumatology case series and review of the literature. Clin Rheumatol 35 , 2457–2462 (2016). [2]Dunleavy, K., Tay, K. &amp; Wilson, W. H. Rituximab-Associated Neutropenia. Seminars in Hematology 47 , 180–186 (2010). [3]Salmon, J. H. et al. Late-onset neutropenia after treatment with Rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry. RMD Open 1 , e000034 (2015). Acknowledgements: The authors would like to thank pharmacist Christine Hay for her help in providing the Rituximab databases. Disclosure of Interests: Mostafa Meshaal Ahmad: None declared, Euan McRorie Speakers bureau: I have spoken at meetings sponsored by Roche several years ago, Consultant of: I have sat on advisory boards for Roche several years ago., Grant/research support from: I was the local investigator for the ORBIT study, published in the Lancet in 2016.