Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

TOCILIZUMAB for GIANT CELL ARTERITIS: BASELINE and TWELVE MONTH AUDIT DATA from the UK BRISTOL and BATH MULTIDISCIPLINARY MEETING

Background: Giant Cell Arteritis (GCA) is a systemic vasculitis involving large and medium-sized blood vessels. Treatment is with high dose glucocorticoids. Steroid-sparing agents and Tocilizumab (TCZ) are used for refractory or relapsing cases. NHS England requires all GCA patients to be discussed in a regional multidisciplinary team meeting (MDT) prior to commencing TCZ. TCZ has only been permitted for a maximum of one year;this time limitation was extended during the Covid-19 pandemic (1). The monthly virtual Bristol and Bath regional MDT started in November 2018. Objectives: We aimed to review: 1) Baseline data on all patients referred to the Bristol and Bath TCZ for GCA MDT, including demographics, clinical presentation and previous steroid-sparing agents used and 2) 12 month follow up data including number of completions, adverse effects, and fares on treatment. Methods: The TCZ MDT referral proforma, adapted from the NHS England Blueteq approval form, was reviewed for all patients referred. 12 month follow up data was obtained from clinic letters. Results: Baseline data Thirty-eight cases were referred between November 2018 and September 2021. Of these, 31 were approved for TCZ usage;100% fulflled the criteria for either refractory (n=11) or relapsing (n=20) disease. Mean age was 74 years and 74.2% were female. Average disease duration was 161.5 days for the refractory and 827.3 days for the relapsing group. 77.4% had cranial GCA, 48.4% had large vessel involvement, 45.2% had visual symptoms and 25.8% had ischaemic visual loss. The positive investigations were PET-CT (48.4%), temporal artery ultrasound (41.9%) and temporal artery biopsy (32.3%). 64.5% had trialled a steroid-sparing agent at time of referral (61.3 % metho-trexate, 9.7% azathioprine, 6.5% lefunomide), 35.5% had received intravenous methylprednisolone and 58% were receiving greater than 40mg prednisolone at the time of referral. Glucocorticoid adverse effects of osteoporosis, weight gain, cataracts and hypertension were each seen in 19.4%;whilst diabetes, neuropsychiatric symptoms and sleep disturbance were each reported in 16.1%. Those with ocular involvement tended to be referred earlier than those without (478.2 days vs 648.1 days), were referred on higher doses of glucocorticoids (71.4% vs 47.1% on ≥ 40mg) and had less steroid-sparing agents prior to referral. Follow up data In December 2021, a follow-up audit revealed 14/31 patients had completed at least 12 months of tocilizumab;5 of these had had an extension under Covid-19 exceptional guidance (mean duration of 5.2 months). Of the remaining 17: 3 patients had stopped early (1 death, 1 moved away, 1 due to adverse effects of headache and gastro-intestinal side effects), 4 had not started tocilizumab and 10 had not completed 12 months of treatment at that point. Adverse events in the 14 patients at 12 months included: liver abnormalities (2/14;14.3%), neutropenia (2/14;14.3%), thrombocytopaenia (1/14;7.1%), soft tissue infections (3/14;21.4%), urinary tract infection (1/14;7.1%) and lipid derangement (4/14 28.6%). One case of GCA relapse occurred on TCZ (mild headache and raised infammatory markers settled on small increase in prednisolone). After 12 months, mean prednisolone dose was 3mg (range 0-15mg). Conclusion: All patients approved for Tocilizumab in the GCA MDT fulflled NHS England criteria for either relapsing or refractory disease. The majority of cases had cranial disease, but almost half had either ocular or large vessel involvement, refecting a severe spectrum of disease. Cases showed a high burden of glucocorticoid toxicity. Follow up data suggests that TCZ was effective in allowing glucocorticoid weaning and disease control, but with some adverse effects. Future work to follow up patients after stopping Tocilizumab would be informative, as the twelve month limitation on treatment is likely to be re-instated.

GIANT CELL ARTERITIS PATIENT PATHWAY: A MULTIDISCIPLINARY APPROACH TO SERVICE IMPROVEMENT IN THE TIME OF COVID-19

Background/Aims The RNHRD is a tertiary rheumatology centre offering a fast-track GCA assessment service. A 2018 departmental audit highlighted areas of good practice including timely assessment of cases but demonstrated irregularities in follow up processes. COVID-19 dramatically changed the way we could deliver our GCA service. Additionally, we saw increases in referrals, confirmed diagnoses and complex disease in our local population during the pandemic. This prompted us to undertake a service improvement project. Our main aims were to optimise follow up in line with national guidelines, enhance patient safety and improve the patient experience. Methods We undertook a service review, starting by mapping the patients' journey. Guidelines were reviewed and stakeholders consulted. We identified several areas for improvement including;consultant-led risk stratification of patients, formalised follow up pathways and closer collaborative working with relevant departments. Additionally, we sought to streamline our processes to accommodate the increased COVID-19 workload. Results A risk stratified follow up pathway was created. Patients are stratified at initial review, by consultants, into low and high-risk pathways. Follow up intervals have been standardised in line with BSR guidance. Follow up patients are reviewed in a dedicated clinic;medical and nursing clinics run supervised by a vasculitis specialist. Patients transfer between different clinics, dependent on clinical stability. Patient information provided has been standardised, with increased emphasis on flare management and steroid side effects. In collaboration with patients this is being incorporated into a 'GCA patient passport', offering a consistent information resource for patients and clinicians. The nurse-led patient advice line is used frequently by GCA patients. All GCA queries are now directed to the on-call registrar, to ensure same day responses. Temporal artery ultrasound is well utilised and completed efficiently;82% of scans between September 2019 and September 2021 occurred within 48 hours of referral. Via close working with vascular ultrasound, we have been able to create dedicated daily ultrasound capacity. Collaborative working with our Ophthalmology department has increased;communication channels between departments have been agreed, and education sessions have been provided. Processes for new GCA patients were streamlined, for example moving location of reviews. This ensured ongoing timely review of new GCA patients despite increased referral numbers. Conclusion COVID-19 had a significant impact on service delivery but provided a catalyst to develop our service. By engaging with stakeholders across disciplines, and reacting to patient feedback, we have been able to institute effective and meaningful change. This process is iterative and we plan further assessment of outcomes including co-morbidities and complications. Further formal patient surveys and development of a GCA expert patient group are underway and will inform further service Development.

Excess giant cell arteritis cases are associated with peaks in COVID-19 prevalence

Background: Immediately following the first wave of the COVID-19 pandemic, the number of giant cell arteritis (GCA) diagnoses noticeably increased at the Royal National Hospital for Rheumatic Diseases in Bath, UK. Furthermore, there was an increase in the proportion of patients with visual complications [1]. The finding supports the viral hypothesis of GCA aetiopathogenesis as previously described [2]. This not only has ramifications for understanding the underlying disease mechanisms in GCA but also has implications for the provision of local GCA services which may have already be affected by the pandemic. Objectives: The objective of the study was to estimate the incidence of giant cell arteritis during the COVID-19 pandemic years of 2020 -2021 and compare it to 2019 data. Given that there have now been two distinct peaks of COVID-19 as reflected by hospital admissions of COVID-19-positive patients this has allowed us to investigate if there is a temporal relationship between the prevalence of COVID-19 and the incidence of GCA. Methods: The incidence of GCA was calculated by assessing emailed referrals to the GCA service and the hospital electronic medical records to identity positive cases from 2019 to the current date. Local COVID-19 prevalence was estimated by measuring the number of hospital beds taken up by COVID-19 positive patients, available publicly in a UK Government COVID-19 dataset [3]. Results: There were 61 (95% Poisson distribution confidence interval [CI] 47 -78) probable or definite GCA diagnoses made in 2020 compared to 28 (CI 19 -40) in 2019 (Figure 1). This is an excess of 33 cases in 2020, or an increase in 118%. Given that 41% of the hospital's catchment population is over 50, this equates to an annual incidence rate of 13.7 per 100,000 in 2019 and 29.8 per 100,000 in 2020. This compares to a previously estimated regional incidence rate of 21.6 per 100,000 for the South West of the UK [4]. A peak in COVID-19-positive inpatients was seen on 10th April 2020 with a corresponding peak of GCA diagnoses on 29th May 2020, giving a lag period of approximately 6 weeks between these peaks (Figure 1). Conclusion: The incidence of GCA in Bath was significantly increased in 2020 compared to 2019. This may be the result of the widespread infection of the local population with the COVID-19 virus as a precipitating factor. Possible mechanisms include, but are not limited to, endothelial disruption by the virus, immune system priming towards T helper cell type 1 (Th1) cellular immunity and/or activation of the monocyte-macrophage system. More work is currently underway to assess the causal relationship between the two diseases. There was a lag period of 6 weeks between the peak during the first wave of the pandemic and the rise in GCA cases. We shall be closely monitoring the number of referrals that follow the current wave of the pandemic.

S75 Hyperpolarised 129-xenon MRI in differentiating between fibrotic and inflammatory interstitial lung disease and assessing longitudinal change

S75 Figure 1Difference between the fibrotic and inflammatory groups in mean 129Xe ADC (a) and LmD (b) at baseline study visit[Figure omitted. See PDF]Conclusions129Xe DW-MRI could have a role in differentiating changes in the airway microstructure between fibrotic and inflammatory ILD. 129Xe RBC:TP has sensitivity to longitudinal change with a decline in gas exchange observed in the fibrotic group but not in the inflammatory group.