<jats:sec><jats:title>Background</jats:title><jats:p>As rituximab (RTX) is a B-cell depleting agent, there are concerns regarding its safety during the COVID pandemic. Data from registries during pre-vaccination period reported increased risk of poor outcomes in RTX-treated patients vs TNFi. However, registry data could be limited by reporting bias in determining true incidence. There are also limited data on breakthrough infections following COVID vaccination.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To assess the incidence of breakthrough infections and predictors of severe COVID outcomes in RTX-treated autoimmune rheumatic diseases (ARDs) with a view to establishing a treatment algorithm for safe RTX administration.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>An observational cohort study was undertaken in the first consecutive 300 ARD patients in a single centre between index date 01/09/2019 (i.e. 6 months prior to pandemic) and 31/01/2022. Only PCR positive cases were included. COVID outcomes were categorised as Mild (i.e. not hospitalised) or Moderate/Severe (i.e. hospitalised and requiring at least oxygenation or death). Predictors of moderate/severe outcomes were analysed using Cox-regression proportional hazard.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Mean (SD) at index date was 59 (14) years, 226/300 (75%) patients were female and 254 (85%) were Caucasians. The diagnoses were RA=212 (71%), SLE=33 (11%), AAV=26 (9%), Sjogren=9 (3%), IIM=8 (3%) and others=12 (4%). Therapy included concomitant DMARDs = 205 (68%) and oral prednisolone = 84 (28%). Median (range) no. of previous RTX courses was 4 (0-19). 534 RTX courses were administered. Of 294 patients with available vaccine data, 17 (6%) were unvaccinated, 4 (1%) had a single dose, 47 (16%) were double-vaccinated, 217 (74%) triple-vaccinated and 9 (3%) quadruple-vaccinated. Of those who were vaccinated, for the first dose, 11% were given within 12 weeks post-RTX, 15% within 26 weeks and 74% were >26 weeks post-RTX. The rate of overall COVID and moderate/severe infections were 11.2/100 PYs and 2.6/100 PYs respectively. Vaccinated patients had lower rate of moderate/severe infection (2.6/100 PYs) vs unvaccinated (18.6/100 PYs) [Table 1]. Over 650.7 PY follow-up, 17/300 patients (5.7%) had moderate/severe COVID including 2 deaths. Factors associated with time-to-infection in imputed multivariable analysis were number of comorbidities [HR 1.46 (95% CI 1.05-2.04)] and low IgG (<6g/L) [6.15 (1.95-19.41)]. A history of COVID vaccination reduced risk [HR 0.13 (0.03-0.51)]. Demographics including concomitant prednisolone, RTX- and vaccine-associated factors (e.g. RTX dose, time from RTX to vaccine, vaccine mode, peripheral B-cell depletion) were not predictive.</jats:p><jats:table-wrap id="T1" position="float" orientation="portrait"><jats:label>Table 1.</jats:label><jats:caption><jats:p>Incidence of COVID infection</jats:p></jats:caption><jats:table><jats:thead><jats:tr><jats:th align="left" rowspan="1" colspan="1" /><jats:th align="left" rowspan="1" colspan="1">Pre-Vaccination Programme</jats:th><jats:th align="left" rowspan="1" colspan="1">Post-Vaccination Programme</jats:th><jats:th align="left" rowspan="1" colspan="1">Overall Follow-up</jats:th></jats:tr></jats:thead><jats:tbody><jats:tr><jats:td valign="top" rowspan="2" colspan="1">Overall COVID rate</jats:td><jats:td rowspan="2" colspan="1">3.3/100 PY</jats:td><jats:td align="left" rowspan="1" colspan="1">Non-vaccinated = 37.7/100 PY</jats:td><jats:td rowspan="2" colspan="1">73 cases in 650.7 years] = 11.2/100 PY</jats:td></jats:tr><jats:tr><jats:td align="left" rowspan="1" colspan="1">Vaccinated = 18.6/100 PY</jats:td></jats:tr><jats:tr><jats:td valign="top" rowspan="2" colspan="1">Moderate/Severe COVID rate</jats:td><jats:td rowspan="2" colspan="1">2.1/100 PY</jats:td><jats:td align="left" rowspan="1" colspan="1">Non-Vaccinated = 15.1/100 PY</jats:td><jats:td rowspan="2" colspan="1">17 cases in 650.7 years] = 2.6/100 PY</jats:td></jats:tr><jats:tr><jats:td align="left" rowspan="1" colspan="1">Vaccinated = 2.6/100 PY</jats:td></jats:tr></jats:tbody></jats:table></jats:table-wrap></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The rate of moderate/severe COVID infection in this cohort is comparable to the pre-pandemic severe infection rate in rituximab trials in RA. The high vaccination uptake in our cohort was effective in preventing severe infection despite the termination of national shielding programme in March 2021 and the spread of the Delta and Omicron variants. Individualised risk–benefit assessment should be undertaken in those with comorbidities, low IgG and unvaccinated when scheduling rituximab therapy.</jats:p></jats:sec><jats:sec><jats:title>References</jats:title><jats:p>None</jats:p></jats:sec><jats:sec><jats:title>Acknowledgements</jats:title><jats:p>This research was funded/supported by the the Wellcome Trust Institutional Strategic Support Fund to MYMY (204825/Z/16/Z), National Institute for Health Research (NIHR) Doctoral Research Fellowship to MYMY (DRF-2014-07-155) and NIHR Clinician Scientist to EMV (CS-2013-13-032). PE is a Versus Arthritis Professor of Rheumatology. This article/paper/report also presents independent research funded/supported by the NIHR Leeds Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.</jats:p></jats:sec><jats:sec><jats:title>Disclosure of Interests</jats:title><jats:p>Md Yuzaiful Md Yusof Consultant of: Aurinia Pharmaceuticals, Jack Arnold: None declared, Benazir Saleem: None declared, Claire Vandevelde: None declared, Shouvik Dass: None declared, Sinisa Savic Speakers bureau: Novartis, Swedish Orphan Biovitrum (SOBI) and Sire, Grant/research support from: Novartis, Swedish Orphan Biovitrum, Octapharma and CSL Behring, Edward Vital Speakers bureau: Roche, GSK and AstraZeneca, Grant/research support from: Roche, GSK and AstraZeneca, Paul Emery Consultant of: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB, Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche.</jats:p></jats:sec>
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