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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
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[Formula presented] Background: Anti-CD20 B cell depleting agents are amongst the most commonly used immunotherapeutics employed in the treatment of haematological malignancy and autoimmune diseases. By inducing peripheral B cell aplasia, anti-CD20 depleting agents are hypothesised to significantly impair serological responses to neoantigens, including the SARS-CoV-2 spike glycoprotein within SARS-CoV-2 vaccines. Seropositivity following SARS-CoV-2 is the strongest, measurable correlate of protection from severe COVID-19. Understanding the kinetics of B cell reconstitution and vaccine responsiveness following exposure to B cell depleting agents is essential to maximise vaccine efficacy in patients vulnerable to severe COVID-19. Methods: 80 patients with underlying haematological malignancy and 38 patients with underlying rheumatological disease previously treated with anti-CD20 B cell depleting agents were studied following their second dose of a SARS-CoV-2 vaccine (median time to sampling: 46.5d, IQR: 33.8-63.3). Lymphocyte subset (CD4, CD8, CD19, CD56/16) enumeration was performed using 6 colour flow cytometry (BD Trucount). Total anti-SARS-CoV-2 spike glycoprotein antibodies were measured by enzyme-linked immunosorbent assay (The Binding Site, Human Anti-IgG/A/M SARS-CoV-2-ELISA). The relationship between immune reconstitution following B cell depletion and vaccine responsiveness was explored. Results: In the haematology cohort (median age 70y, IQR 60.3-76.0, 62.5% male), overall seropositivity following vaccination was 60.0%. Individuals on active chemotherapy had significantly lower seroprevalence than those vaccinated following the completion of chemotherapy (22.7% vs 74.1%, p<0.0001). In the rheumatology cohort (median age 65y, IQR 58.3-70.8, 39.9% male), overall seropositivity was 69.4%. In both cohorts, vaccine non-responders had significantly smaller populations of peripheral CD19+ B cells (haematology: 0.20 vs 0.02 x10 9/L, p=0.004, rheumatology: 0.07 vs 0.01 x10 9/L, p=0.03). The magnitude of the antibody response following vaccination did not differ between recipients of Tozinameran and Vaxzeveria in either cohort. Vaccine responsiveness was lower in the first 6 months following B cell depletion therapy;42.9% in the haematology cohort and 33.3% in the rheumatology cohort, increasing to 100% and 75% respectively in individuals receiving their second dose 6-12 months following B cell depletion (Figure 1). B cell reconstitution in the 7-12 month window following B cell depletion was faster in haematology compared to rheumatology patients (77.8% v 22.2% achieving normal B cell count, p=0.005) and associated with improved vaccine responsiveness. However, persistent immunodeficiency occurred in some haematology patients following completion of treatment: 25% of patients who had completed therapy at least 36 months previously failed to respond to vaccination. In this cohort of vaccine non-responders, 83.3% of individuals had B cell numbers within the normal range. These patients had all previously been treated for follicular lymphoma suggesting a specific mechanism for long-range secondary immunodeficiency in these patients. Conclusions: Serological responsiveness to SARS-CoV-2 vaccines is poor during active chemotherapy for haematological malignancy and in the first 6 months following B cell depletion, regardless of underlying disease. Vaccine responsiveness significantly improves in the 7-12 month window following B cell depletion. Compared to haematology patients, B cell reconstitution is slower in rheumatology patients and associated with reduced vaccine responsiveness, possibly due to the use of additional concurrent disease-modifying anti-rheumatic therapies. Furthermore, long-term secondary immunodeficiency occurs in a minority of haematology patients. To maximise the efficacy from SARS-CoV-2 booster vaccination and optimal utilisation of available vaccine doses, immunisations should be delivered at least 6 months following the administration of anti-CD20 depleting drugs. Figure 1: Kinetics of return f vaccine responsiveness following B cell depletion in haematology and rheumatology patients. [Formula presented] Disclosures: Paneesha: Roche: Honoraria;Janssen: Honoraria;Gilead: Honoraria;Bristol Myers Squibb: Honoraria;AbbVie: Honoraria;Celgene: Honoraria. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company.
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Background: Worldwide the detrimental consequences of the COVID-19 pandemic on physical and psychological health have been recognised. Social distancing and isolation measures have negatively impacted physical functioning (PF) and mental health (MH), and are known to have reduced physical activity (PA) generally within the population. A significant proportion of patients with autoimmune rheumatic disease (ARD) are considered 'clinically extremely vulnerable' (CEV), at high risk from COVID19 and been advised to follow stricter social distancing precautions than the general population. Evidence in ARD patients highlights the importance of PA in maintaining physical and psychological wellbeing. Prior to the pandemic limitations in both PF and MH in patients with ARD were recognised and early in the pandemic MH was noted to be impacted by distancing measures in this population. Objectives: This is an interim report of a research study (clinicaltrials.gov NCT04542031) exploring the impact of the COVID19 pandemic on the physical and psychological wellbeing of patients with rheumatic disease, to inform guidelines and target service provision as the pandemic continues. Methods: We distributed two web-based surveys, eight months apart during the first (April-2020) and second wave (December-2020) of the pandemic. Surveys were communicated via a linked mobile-phone SMS message, to all rheumatology patients with a validated mobile number under follow-up at the Royal Wolverhampton Trust. We assessed patients using the Short Form-12 version 2 made up of mental (MCS) and physical component scores (PCS). For each survey, data were collected 4-weeks following distribution;comparative analysis was conducted using SPSS version-27. Results: Initial surveys were sent to 7911 active follow up patients;1694/7911 (21.4%) responded and consented for further follow up, of which 1636 were linked to a validated mobile number. 899/1636 (55.0%) responded to the second survey and 824/899 (91.7%) responses were linked across both surveys. These 824 patients were predominately female (69.5%), aged 61 years and 76.3% had an ARD;388/824 patients were CEV, 436 were in the comparator group. For the CEV group, scores remained significantly lower than the comparator for PCS (survey 1: 36.40 vs 39.61 [P<0.001], survey 2: 36.11 vs 38.66 [P<0.001]) and MCS (41.61 vs 43.44 P<0.001;41.19 vs 43.60 [P<0.001]);there was no deterioration in CEV scores. In the comparator group, while MCS did not differ in patients with ARD, PCS significantly decreased (1.39;95% CI: 0.69, 2.08;P<0.001);PCS in the non-inflammatory group did not significantly change (-0.23, P=0.65). Conclusion: These preliminary data suggest that while the physical and mental health of CEV patients is significantly lower in this cohort, surprisingly, neither aspects of health have been worsened by the impacts of the pandemic over an 8-month period. However, the physical functioning of patients with ARD significantly decreased in this time, which may reflect the reduction in PA faced by society, and reduced contact with secondary care services. These data suggest services need to adapt to provide additional support to patients with ARD to maintain physical functioning during the pandemic. Further work exploring the evolving pattern of the physical and psychological responses to the pandemic is ongoing.
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Background: There are reported concerns of patient misunderstanding of the COVID-19 pandemic and vaccination safety. It is particularly important that these are understood in patients taking complex immunusuppressive therapies. Rapid delivery of targeted and up-to-date video messages from clinicians sent directly to patients could address patient uncertainty, and improve COVID-19 vaccination uptake. Innovative SMS (short message service) based video message has already shown promise in delivering COVID-19 information to patients [1]. We present our experience in creating a tailored vaccine information video sent directly to our large cohort of patients in the UK with a range of rheumatic diseases and report on the learning points going forward. Objectives: Our three objectives were: (1) educate our patients using an interactive mobile video information resource outlining the safety of the COVID vaccination in these patient groups;(2) better understand our patients' views of the COVID-19 vaccine;(3) evaluate the patient experience of this approach. Methods: We designed and recorded an 8-minute interactive web-based video delivered education resource designed for mobile phones. This included: aims of the video;details of licenced vaccines;UK vaccination schedule;frequently asked questions;links to national charity resources;our clinician recommendations;a rheumatologist being vaccinated;case studies;and summary data. We produced a simple mobile phone web-based evaluation of the resource, including anonymised patient demographics, their understanding of the safety of the vaccine pre/ post video, and their user experience. Resource and evaluation were piloted by local healthcare professionals, our Patient Participation Group, a national charity, and approved by senior management. We distributed this to our follow-up patient cohort via our hospital SMS provider on 21.12.20, at the start of roll-out of UK vaccines, containing a link to the resource and evaluation. Results: Of a cohort of 10,981 patients, we had 8886 mobile phone numbers. At Day 14, we recorded 2358 video views (26.3%) and 664/2358 completed evaluations (28.1%). Only one person reported being unable to watch the video. Before watching the video, 348/664 patients (52.4%) were unsure if the vaccine was safe and/or recommended for them, rising to 626/664 (94.3%) post-video. Reasons for uncertainty after the video (38/664) included drug allergy and fertility concerns. Following the video, 509/664 patients (76.6%) reported that they were more likely to have the vaccination. The majority of the patients (614/660, 93.0%) agreed that the method was a helpful method to share such information.Age distribution of our whole cohort, patients with mobile phones, and responders were similar: Age >50 was 80.4%,76.3%,and 88.6% respectively. A large proportion was treated with immunosuppressive medication (61.3% conventional DMARD, 39.4% biological DMARD and 17.6% corticosteroids). Gender and case mix for responders were similar to published data from our cohort: female 74.0%;rheumatoid arthritis commonest disease (389/664, 58.5%). Conclusion: To our knowledge, this is the first study to show the potential for SMS linked interactive multimedia message for patient education. The multimedia component allows users to easily navigate to relevant sections, and access a choice of linked resources. We demonstrate this low-cost technology is simple, effective and well placed to assist physicians in educating patients during a time when face-to-face contact is proving to be difficult. We have shown high levels of patient satisfaction, reassurance, and self-reported behaviour change. Such technology has potential utility for national bodies, primary and secondary care groups, and merits further research.
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Background/AimsCOVID-19 has created numerous challenges for people globally. In theUK, few studies have reported poorer outcomes for certain ethnicpopulations. UK government introduced shielding guidance to protectthe most vulnerable patients and this was in force for a number ofmonths. However, shielding guidance was initially released only inEnglish, which resulted in further disenfranchisement of the Black, Asian and Minority Ethnic community (BAME). We undertook an auditto understand experiences of shielding particularly in rheumatologicalBAME patients in multi-ethnic communities in 3 centres -Wolverhampton, Leicester and Oxford.MethodsThis study was approved in all three sites as an audit. Patientscontacting rheumatology helpline or having routine consultations wereincluded. Each centre aimed to recruit at least 20 patients. Aquestionnaire was developed to capture important data on shielding.The study was conducted between May and June 2020 during thepeak of the first wave of Covid 19.ResultsWe recruited 79 patients into this audit, of these 54 were of BAME and25 of Caucasian ethnicity with 17 males and 62 females. RheumatoidArthritis (RA) was the commonest diagnosis in 49 of these patients(62%) and these patients were older (median ages 56 vs. 46 years, p = 0.14). BSR risk scoring algorithm was used to determine need forshielding (BSR score of 3 or more) - 38 patients fell into this category.The remaining patients had scored lower and had the option ofshielding or enhanced social distancing. Of the 13 Caucasian patientswho should have been shielding, 11 were (85%). Of the 25 BAMEpatients who should have been shielding: 17 were, and 8 were not(68%, p = 0.26;65% looking at South Asian patients alone).Understanding of reasons for shielding was clear for 21 out of 25Caucasian patients (84%). In contrast, 33 of 54 patients from BAMEbackgrounds (61%) were clear on this (p = 0.10). WithinWolverhampton and Leicester, the numbers are starker with 20 outof 37 (54%) being clear on this. Very few Caucasian patients madechanges to their existing medications with 84% carrying on theirmedications as they were before the onset of COVID 19. However, of54 BAME patients, 14 patients had stopped medications - either bythemselves or as per advice of health professionals (74%, p = 0.16).There was a significant difference between centres in patientsstopping medications with patients from Leicester much more likely(p < 0.001).ConclusionDespite the small numbers, the data clearly suggest that BAMEpatients were less likely to understand the reasons for shielding, tofollow shielding advice, and more likely to change their medications, thereby risking a flare. Addressing culturally competent educationalneeds and health equality for BAME rheumatology patients continuesto remain a challenge.
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OBJECTIVES: We sought to gain insight into the prevalence of COVID-19 and the impact stringent social distancing (shielding) has had on a large cohort of rheumatology (RD) follow-up patients from a single large UK centre. METHODS: We linked COVID-19-related deaths, screening and infection rates to our RD population (1.2.20-1.5.20) and audited active rheumatology follow-up patients through survey data communicated via a linked mobile phone SMS message. We assessed epidemiology, effect of stringent social distancing (shielding) and quality of life (HRQoL) by Short Form 12 (SF12). RESULTS: There were 10,387 active follow-up patients, 7911 had linked mobile numbers. 12/10,387 RD patients died from COVID-19 (0.12%); local population 4131/7,415,149 (0.12%). For patients with mobile phones, 1693/7911 (21%) responded and of these, 1605 completed the SF12. Inflammatory arthritis predominated 1174/1693 (69%); 792/1693 (47%) were shielding. Advice on shielding/distancing was followed by 1372/1693(81%). 61/1693 (4%) reported COVID-19 (24/61 shielding); medication distribution was similar in COVID and non-COVID patients. Mental SF12 (MCS) but not physical (PCS) component scores were lower in COVID (60) vs. non-COVID (1545), mean differences: MCS, - 3.3; 95% CI - 5.2 to - 1.4, P < 0.001; PCS, - 0.4; 95% CI, - 2.1 to 1.3). In 1545 COVID-negative patients, those shielding had lower MCS (- 2.1; 95% CI - 2.8 to - 1.4) and PCS (- 3.1, 95% CI - 3.7 to - 2.5), both P < 0.001. CONCLUSIONS: Our full RD cohort had no excess of COVID deaths compared to the general local population. Our survey data suggest that shielding adversely affects both mental and physical health in RD. These data broaden our understanding of shielding, indicating need for further study.