OUTCOME FOR PATIENTS WITH GIANT CELL ARTERITIS (GCA) TREATED WITH TOCILIZUMAB ACCORDING TO NICE GUIDANCE IN A SINGLE TERTIARY UK CENTRE

BackgroundIn 2018 NICE and NHS England approved one year of weekly subcutaneous tocilizumab for use in relapsing or refractory GCA [1, 2]. During the COVID pandemic NHS England allowed extended use of tocilizumab in selected high risk patients [3]. This extension ended in March 2022. This has created a cohort of patients who are now no longer treated with tocilizumab and may be at risk of GCA flare. Currently, NHS England does not allow retreatment with tocilizumab.ObjectivesThis service evaluation used an intention-to-treat approach to retrospectively evaluate patients, who were ratified to receive tocilizumab for GCA according to the NICE guidance. We aimed to describe this cohort of patients for whom the use of tocilizumab had been approved, and their outcomes in terms of complications and disease control.Methods49 patients were ratified to receive tocilizumab between May 2019 and April 2022 by a specialist multidisciplinary team at a single tertiary rheumatology center. Their response was assessed in terms of relapse rates, steroid usage and complications as described below.Results80% of the 49 cohort of patients consisted of females (Table 1). 55% of patients were diagnosed with GCA on combination of clinical history, laboratory and temporal artery duplex findings. 94% (46/49) had at least a week's course of tocilizumab. Around half (51%) had relapsing disease. 6% had first dose as intravenous due to critical ischaemia. 27% (13/49) of patients developed complications whilst on treatment. Six developed cytopenia, 3 acquired infections and 4 stopped due to other reasons. As per guidelines, tocilizumab was stopped after 12 months in 25 patients (51%). 16% stopped treatment early due to complications. 18% had incomplete information. 10% had ongoing treatment. One patient died several months after finishing tocilizumab. 47% had methotrexate as DMARD therapy added prior to tocilizumab commencement (Figure 1). Out of 25 patients who completeted treatment, 24% (6/25) relapsed. 83% of these relapses were diagnosed on recurrence of symptoms and high inflammatory markers. In addition, 3 patients, who had tocilizumab suspended relapsed. 2/3 of these patients had treatment suspended due to infection. 5/9 relapse patients did not have preceding DMARD therapy. 22% (2/9) of relapse patients had PET-CT due to involvement of extra-cranial disease. 56% (5/9) relapsed following a median follow-up of 11 months. Of relapsed patients, seven were treated with increased dose of prednisolone and two patients received 6 months extension of tocilizumab with adequate tolerance and efficacy.ConclusionOur data shows good tolerability of tocilizumab and a 24% flare rate amongst patients who completed treatment. This is less than the 50% rate seen in GiACTA and other cohorts, where the majority of which occurred within 6 months of stopping treatment [4]. DMARD treatment may reduce relapse rate, but this will require further study. The data describing the efficacy of treatment beyond one year is limited [3]. However, with no established guidance for treating patients following tocilizumab, extension of treatment is a plausible option.References[1]Tocilizumab for treating giant cell arteritis, NICE Technology Appraisal Guidance, 18 April 2018. https://www.nice.org.uk/guidance/ta518/resources/tocilizumab-for-treating-giant-cell-arteritis-pdf-82606786726597[2]Stone J, Tuckwell K, Dimonaco S et al.Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377:317-328.[3]Regola F, Cerudelli E,Bosio G. Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients Rheumatology Adv Pract 2020;0:1–9.[4]Conway R, Putman MS, Mackie SL. Benchmarking tocilizumab use for giant cell arteritis. Rheumatol Adv Pract. 2022;6(2):rkac037.Figure 1.Table 1.GenderAge at time of diagnosisIndication for stopping treatmentMaleFemale50-5960-6970-7980-89Completed treatmentComplicationsOngoing treatmentIncomplete information18313162010251058Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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

Use of Accelerometers to Track Changes in Stepping Behavior With the Introduction of the 2020 COVID Pandemic Restrictions: A Case Study

Introduction: The COVID-19 lockdown introduced restrictions to free-living activities. Changes to these activities can be accurately quantified using combined measurement. Using activPAL3 and self-reports to collect activity data, the study aimed to quantify changes that occurred in physical activity and sedentary behavior between prelockdown and lockdown. The study also sought to determine changes in indoor and outdoor stepping. Methods: Using activPAL3, four participants recorded physical activity data prelockdown and during lockdown restrictions (February–June 2020). Single events (sitting, standing, stepping, lying) were recorded and analyzed by the CREA algorithm using an event-based approach. The analysis focused on step count, sedentary time, and lying (in bed) time;median and interquartile range were calculated. Daily steps classified as taking place indoors and outdoors were calculated separately. Results: 33 prelockdown and 92 in-lockdown days of valid data were captured. Median daily step count across all participants reduced by 14.8% (from 5,828 prelockdown to 4,963 in-lockdown), while sedentary and lying time increased by 4% and 8%, respectively (sedentary: 9.98–10.30 hr;lying: 9.33–10.05 hr). Individual variations were observed in hours spent sedentary (001: 8.44–8.66, 002: 7.41–8.66, 003: 11.97–10.59, 004: 6.29–7.94, and lying (001: 9.69–9.49, 002: 11.46–11.66, 003: 7.63–9.34, 004: 9.7–11.12) pre-and in-lockdown. Discrepancies in self-report versus algorithm classification of indoor/outdoor stepping were observed for three participants. Conclusion: The study quantitively showed lockdown restrictions negatively impacted physical activity and sedentary behavior;two variables closely linked to health outcomes. This has important implications for public health policies to help develop targeted interventions and mandates that encourage additional physical activity and lower sedentary behavior. © 2023 Human Kinetics, Inc.

Agents of Change: Modeling Two-Year College English Teachers' Change Resilience and Saturation during COVID and (we hope) Beyond

In the face of the pandemic, teachers sought to rapidly incorporate new technologies and maintain or expand meaningful relationships with their students. We created a survey to capture the lived experiences of this moment and bear witness to teachers' frustrations and triumphs during this time. In addition to reports of exteme burnout and emotional labor, we discovered possibilities for changes that contributed to teachers' greater resilience. In this article, we share experiences of change saturation and change resilience to illustrate the conditions we hope to foster in order to sustain the radical teaching practices of teaching with compassion. © 2022, University Library System, University of Pittsburgh. All rights reserved.

COLLABORATION WITH CARE HOMES TO PROVIDE APPROPRIATE MEDICAL CARE IN THE PANDEMIC

Background The Acute Clinical Team (ACT) in Neath Port Talbot is a well-established hospital at home service that provides treatments in the community. During the COVID 19 outbreaks, the team proactively telephoned the care home managers on a regular basis to enquire about the residents wellbeing and establish if input was required. This proactive approach worked well with some homes. Where crises developed, we were able to provide hands on support to provide appropriate medical care. Methods A collaborative effort from community teams and volunteers assisted ACT to provide nursing and medical interventions in care homes which accepted our help. Interventions included intravenous (IV) antibiotics, parenteral fluids, IV/oral dexamethasone, low molecular weight heparin, oxygen (up to 10 L face mask), communication with families and palliative care. Results Data is presented from 7 care homes for which ACT provided input;patients who were unwell requiring additional help were referred to the team. Comparative data from a care home in the same area where ACT was not involved is presented. Data was collected from 01/11/20-10/02/21. Table 1 Care homes with ACT involvement (190 patients) Care home without ACT involvement (85 patients) Patients assessed Patients not assessed No. with COVID-19 infection (%) 96/190 (51%) 94/190 (49%) 27/85 (32%) Acute hospital admission related to COVID-19 (%) 3/96 (3%) 7/94 (9%) 8/27 (30%) Died within 28 days of positive test(%) 37/96 (39%) 20/94 (21%) 15/27 (56%). Conclusion ACT had a vital role during the outbreak in supporting the local community. The team was able to provide a range of interventions and prevent avoidable admissions. The team received excellent feedback ‘We couldn’t have survived without the ACT teams input. They were our lifesavers. The whole team were amazing and came to our rescue where everyone else who knew we had COVID bolted to the hills’ Manager.

Audit of prostanoid use in severe Raynaud'sand adherence to treatment of digital ulcers inpatients with SSc NHSE pathway: Commissioningpolicy cost analysis and alternative therapeuticpathway proposed

Background/AimsSevere Raynaud's phenomenon (RP) can lead to digital ulcers (DU), ischaemia, infection and gangrene. In 2015, NHS England published a commissioning policy enabling the use of bosentan fordigital ulceration in SSc in patients refractory to intravenous 6-8weekly prostanoid in combination with sildenafil following standardtherapy (including calcium channel blockers (CCB), ACE inhibitors, losartan and fluoxetine). Bosentan is licensed to prevent newDUs in SSc. Specialist MDT ratification and Blueteq registration isrequired. RCTs showed bosentan reduced the formation of newDU by 30-50% in at risk individuals. It is a well-tolerated drug. It isnow off-patent so its cost has reduced from £22, 000 to £650 peryear.AimTo audit current departmental practice in patients receiving prostanoid(epoprostenol) for severe RP from any cause and check adherence tothe patient pathway for treatment escalation prior to prostanoidtherapy. To determine approximate costs of alternative therapeuticapproaches. MethodsWe retrospectively audited patients attending our day unit forepoprostenol infusions over a 12-month period between 2018 and2019. Using our centre's admissions database and electronic patientrecords, we identified which oral medications patients were currentlyco-prescribed or had previously trialled. Using pharmacy data andtariff costings, we calculated the cost of epoprostenol infusions andoral medications with blood monitoring.ResultsBetween 2018 and 2019, 73 patients attended for epoprostenolinfusions: 31 SSc, 25 RP, 17 other diagnoses (mixed/undifferentiatedCTD, SLE, vasculitis). The mean number of epoprostenol infusions perpatient per year was 5.92 days (range 1-25). The percentage ofpatients who had first been trialled on the following medicationsinclude: CCB 77.4%, ACEi/ARB 41.1%, fluoxetine 9.59%, sildenafil87.1% and tadalafil 25.8%. In the SSc group 22.6% had also trialledbosentan. Only 2 SSc patients (6.45%) had trialled all of the drugs onthe pathway prior to prostanoid reflecting the relative lack of efficacy ofsome first line therapies. The departmental tariff per prostanoidinfusion is £450, resulting in an estimated average annual cost of£2700 per patient. The annual cost of supplying bosentan 125mg twicedaily plus blood monitoring for the first year is approximately £1350.ConclusionEpoprostenol is used in our unit for patients with severe RP from arange of conditions. Sildenafil and CCB have been trialled in themajority of our patients prior to escalation. Only a minority of patientshave received bosentan according to current guidelines and licensing.Given the reduction in cost, combined with the importance of avoidinghospital admissions with COVID-19, we would suggest that bosentancould be used earlier in the treatment pathway for a broader range ofindications. NHSE is revising the SSc commissioning policy.

A pediatric case series evaluating the benefits of combined bronchoscopy and CT in ECMO

Objective: To evaluate the benefit of thoracic computed tomography (CT) and flexible fibreoptic bronchoscopy (FFB) on ECMO in a paediatric case series. Methods: Retrospective review of all children on ECMO during years 2018-2020 who underwent both CT and FFB at Evelina London. Centre policy is to undertake CT chest for all respiratory patients using inspiratory and expiratory phases with angiography. FFB is performed for patient specific concerns. Results: Of 51 patients receiving ECMO, 10 patients (19.6%) underwent both procedures and one had angiography instead of CT. Eight patients were supported on VV-ECMO, three on VA-ECMO. 26 FFB were performed in 11 patients (range 1-5 per patient). FFB cleared the airway from mucous plugs in three patients after phased CT showed significant areas of dynamic air trapping, including one patient with COVID-19 pneumonia. FFB was used in three patients with pulmonary haemorrhage: it enabled packing of the trachea in one patient who received coiled embolization of the pulmonary artery (PA) and granted extensive airway lavage (vasculitis in first patient and post Glenn procedure for hypoplastic left heart syndrome in second). CT confirmed the diagnosis in two patients, the third patient required angiography demonstrating collaterals subsequently coiled. CT with FFB identified PA narrowing and contralateral main bronchus compression post cardiac repair, guiding the ventilation strategy. FFB was used to place a nasal endotracheal tube in a patient with difficult airway whose existing tracheostomy site was infected. CT wasn't beneficial in this patient. Pulmonary embolism on CT was identified in one patient guiding increased anticoagulation strategy. FFB and CT excluded traumatic injuries in a newborn with respiratory failure and pneumomediastinum. Conclusions: Both FFB and CT gave a clear therapeutic benefit in 10/11 patients on ECMO with complementary diagnostic information.

Covid-19 mortality review: Current smokers Are under-represented and cannot be Explained by ethnicity alone

Aim To compare demographic information between COVID-19 related deaths and those who died of another cause to identify any significant patient factors that may be contributing to COVID-19 deaths. Methods A retrospective systematic review of all medical (acute, general internal, specialty and critical care) mortality was undertaken from 01/03/2020 until 01/07/2020 in a large inner-city hospital. The electronic medical record from both the hospital and GP (where available) were reviewed to identify demographic information with particular reference to characteristics thought to be associated with COVID-19 illness including age, gender, ethnicity and co-morbidities. Death certificate information was used to establish direct cause of death (part 1 a, b or c). Only deaths where death certification was available were included. Results Death certification was available for 279 deaths (median age 77 years;IQR 67-83;133 (48%) female;76 (27%) BAME;67 (24%) admitted to critical care). 121 (43%) died as a direct consequence of COVID-19 illness (median age 77 years;IQR 67-83;61 (50%) female;47 (39%) BAME;31 (26%) admitted to critical care). Non-Caucasian (BAME) ethnicity was associated with increased COVID-19 mortality (RR 1.67;95% CI 1.30-2.15;p 0.0015). BMI, COPD, hypertension, chronic kidney disease and renal replacement therapy were not independent risk factors for COVID-19 deaths compared to deaths by another cause (see table 1). In comparison, type 2 diabetes was stastically associated with COVID-19 deaths (RR 1.3;CI 1.01-1.71;p 0.045). Current smoking status was negatively associated with COVID-19 mortality (RR 0.33;95% CI 0.16-0.65;p 0.0015) with 5.8% current smokers in COVID-19 deaths compared to 23.7% in those who died of another cause. Smoking status was not available for 4 persons (1.4%). Conclusion In our cohort, there appears to be increased mortality from COVID-19 associated with BAME ethnicity and type 2 diabetes. The signal from current smoking status is interesting and cannot fully be explained by ethnicity alone and should prompt further research.

S5 COVID-19 mortality review: current smokers are under-represented and cannot be explained by ethnicity alone

S5 Table 1Commonest co-morbidities for certified deaths related and not related to COVID-19 illness March to July 2020ConclusionIn our cohort, there appears to be increased mortality from COVID-19 associated with BAME ethnicity and type 2 diabetes. The signal from current smoking status is interesting and cannot fully be explained by ethnicity alone and should prompt further research.