ABSTRACT
BackgroundIn inflammatory arthritis patients, the concomitant decline of their mental wellbeing is an increasing concern[1,2]. It is important to not only describe the trajectory of psychological distress in early disease stages, but also understand which clinical outcome measures are most associated with these changes.ObjectivesUsing data from the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological wellbeing over 12 months after initial diagnosis and mapped these against clinical outcomes to identify significant associations.MethodsNEIAA collects data from patients referred with suspected early inflammatory arthritis in rheumatology services in England and Wales. We used data provided by 20,472 patients eligible for follow-up (diagnosis of inflammatory arthritis) between May 1st, 2018, and April 1st, 2022. Data items included baseline demographics e.g., age and gender, and clinical variables e.g., rheumatic disease comorbidity index (RDCI), DAS28, and patient reported outcomes.Psychological distress was measured by the sum score of Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS). Using mixed effects regression models, we analysed the co-variability of PHQ4ADS with demographic factors and clinical outcomes over 12 months. Time was included as a dummy-coded covariant.ResultsThe analysis included 36% of patients (7,378 out of 20,472) who completed the baseline patient outcome survey. In this cohort, PHQ4ADS scores decreased from a baseline average of 4.7 (CI: [4.6, 4.8]) to 2.62 (CI: [2.5, 2.8]) at 12 months post-diagnosis. The proportion of patients screening positive decreased from 50.0% (CI: [48.9, 51.1]) at baseline to 23.8% (CI: [21.8, 25.9]) at 12 months.At baseline, psychological distress correlated significantly with age, gender, ethnicity, RDCI, prior depression diagnosis, and baseline DAS28 (Figure 1). No significant correlations were found between psychological distress and working diagnosis, seropositivity, or the assessment being recorded after the start of the COVID-19 pandemic. Younger ages were nonlinearly associated with higher distress levels (coefficient per decade: -0.006;p<0.001;CI: [-0.009, -0.003]) (Figure 1a). Distress levels in females were higher than that of males (coefficient: 0.5;p<0.001;CI: [0.4, 0.7]) (Figure 1b). White patients reported lower PHQ4ADS scores compared to non-white patients (coefficient: -0.7;p<0.001;CI: [-1.0, -0.4]) (Figure 1c). Higher distress levels were also associated with higher RDCI (coefficient: 0.2;p<0.001;CI: [0.1, 0.3]) and prior diagnosis of depression (coefficient: 1.8;p<0.001;CI: [1.5, 2.2]) (Figure 1d, 1e). Furthermore, higher baseline DAS28 scores correlated with more severe psychological distress (coefficient: 0.8;p<0.001;CI: [0.7, 0.8]) (Figure 1f).By 12-months, psychological distress decreased significantly overall, which correlated significantly with ethnicity (coefficient: 0.8;p=0.005;CI: [0.3, 1.4]) and baseline DAS28 (coefficient: -0.5;p<0.001;CI: [-0.6, -0.4]). Compared to white patients, the reduction was significantly greater for non-white patients, but the level of distress was no longer different at 12 months (Figure 1c). While those with higher baseline DAS28 showed a greater reduction in psychological distress, the distress levels remained higher at 12 months (Figure 1f).Figure 1.Changes in psychological distress correlated with age, gender, ethnicity, RDCI, prior depression diagnosis, and baseline DAS28.[Figure omitted. See PDF]ConclusionIn this early inflammatory arthritis cohort, mental health burden was high. Age, gender, ethnicity, RDCI, prior depression diagnosis and baseline DAS28 significantly correlated with psychological distress at baseline. Supporting mental health should be a focus of clinical care for this population and it may be beneficial to use an approach that is culturally valid for non-white patients and accounts for multimorbidity.References[1]Euesden, J, et al. Psychosomatic medicine 79.6 (2017): 638.[2]Lwin, MN, et al. Rheumatology and therapy 7.3 (2020): 457-471.AcknowledgementsThe authors would like to thank the Healthcare Quality Improvement Partnership (HQIP) as the commisioner of NEIAA, British Society for Rheumatology as the audit providers, Net Solving as the audit platform developers, and the Wellcome Trust (ST12406) for funding to support L.Z..Disclosure of InterestsLucy Zhao: None declared, James Galloway Speakers bureau: Has received honoraria from AbbVie Celgene, Chugai, Gillead, Janssen, Eli Lilly, Pfizer, Roche, and UCB, Jo Ledingham: None declared, Sarah Gallagher: None declared, Neena Garnavos: None declared, Paul Amlani-Hatcher: None declared, Nicky Wilson: None declared, Lewis Carpenter Consultant of: Statistical consultancy for Pfizer, Kirsty Bannister: None declared, Sam Norton Speakers bureau: Has received honoraria from Janssen and Pfizer.
ABSTRACT
BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.
ABSTRACT
Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care;2) time to first rheumatology assessment;3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days;IQR 8-35 days) than before (21 days;9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic;however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic;however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinelycaptured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.
ABSTRACT
Background: There has been a major concern about the impact of COVID-19 in patients with infammatory arthritis during the pandemic, with recommendations from governments for patients to shield. Objectives: Our aim was to describe the risk factors for COVID-19 hospitalisation and mortality amongst patients recruited to the National Early Infammatory Arthritis Audit (NEIAA) in England. Methods: An observational cohort study design was used. The population included adults in England with new diagnoses of infammatory arthritis between May 2018 and March 2021 who enrolled in NEIAA. The outcomes were hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition) and death due to COVID-19 (COVID-19 stated on a death certifcate), identifed via linkage with secondary care records. Hazard ratios were calculated using Cox proportional hazards models, with adjustment for patient factors (age, gender, smoking status, and comorbidity) and disease factors (seropositivity, 28-joint disease activity score, patient-reported disability (HAQ), and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from the date of diagnosis or February 2020 (whichever was later) and censored at a COVID-19 event, death or May 2021 (whichever was sooner). Results: 14,127 patients were included. The mean age was 57 years;62% were female;19% were current smokers, while 29% were ex-smokers. The frequency of comorbidities at baseline were: hypertension (19%), diabetes mellitus (9%), and lung disease (9%). Overall, 20% had two or more comorbidities. Rheumatoid factor or CCP antibodies were positive in 56%. At presentation, mean scores for DAS28 were 4.6 (+/-1.5), 1. 1 (+/-0.7) for HAQ, and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients: methotrexate was the most common (54%), followed by hydroxychloroquine (23%), and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 [95% CI: 0.79-1.10] and death: 0.31 [95% CI: 0.23-0.41]. Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 hospitalisation and death. Higher baseline DAS28 predicted COVID-19 hospitalisation (HR 1.24 [95% CI: 1.10-1.39]) and mortality (HR 1.33 [95% CI: 1.09-1.63]). Higher HAQ predicted both COVID-19 hospitalisation and death. Seropositivity was not a signifcant predictor of any COVID-19 event, nor was MSK-HQ. In unadjusted models, corticosteroids associated with COVID-19 death (HR 2.29 [95% CI: 1.02-5.13], and sulfasalazine monotherapy associated with COVID-19 hospitalisation (HR 1.93 [95% CI: 1.04-3.56]. In adjusted models, associations for corticoster-oids and sulfasalazine were no longer signifcant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion: The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic, with concerns about the use of csDMARDs and corticosteroids.1,2 Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.
ABSTRACT
Background: There has been considerable uncertainty about the impact of biologic DMARDs (bDMARDs) on COVID-19 morbidity and vaccine efficacy, which may have influenced prescribing during the pandemic. Objectives: To assess trends in the prescription of three commonly used bDMARDs with different modes of action-adalimumab (ADA), rituximab (RTX) and tocilizumab (TOC)-in England before and during the COVID-19 pandemic. Methods: The National Health Service (NHS) Secondary Care Medicines dataset was utilised to analyse temporal trends in bDMARD prescriptions issued by all NHS hospital pharmacies in England. Monthly averages of prescriptions issued for ADA, RTX and TOC for combined indications, standardised using WHO Defned Daily Doses (DDD), were described from January 2019 to November 2021. Interrupted time-series analyses (ITSA) were used to estimate the effect of the pandemic on prescription trends for ADA, RTX and TOC;Newey-West standard errors with lags were used to account for autocorrelation between observation periods in these models. Results: Temporal trends in ADA, RTX and TOC prescriptions are shown in Figure 1. A 46% decrease in RTX prescriptions was observed between March and April 2020, from 1,338,300 DDD to 718,900 DDD, respectively, coinciding with the worsening COVID-19 pandemic in England. RTX prescriptions increased after May 2020, refected in the positive prescription trend observed in ITSA models (Table 1);however, RTX prescriptions remained below pre-pandemic levels, before decreasing again between November 2020 and February 2021. This coincided with increasing COVID-19 case numbers in England. For ADA, the pre-pandemic trend of increasing prescriptions continued during the pandemic, with no differences in prescription trends seen in ITSA models (Table 1). A 22% decrease in ADA prescriptions was observed between September and October 2020, from 2,037,800 DDD to 1,587,500 DDD, respectively, before rebounding to above pre-pandemic levels. Prescriptions for TOC increased during the pandemic, driven primarily by a 76% increase in prescriptions between December 2020 and January 2021, from 241,800 DDD to 425,000 DDD, respectively. Conclusion: Prescriptions for RTX in England halved during the early COVID-19 pandemic, and remain below pre-pandemic levels as of November 2021. This likely refects concerns about RTX use and increased COVID-19 mortality and reduced vaccine efficacy.1,2 In contrast, prescriptions for ADA have continued to increase during the pandemic, while prescriptions for TOC surged in December 2020, coinciding with the more widespread use of TOC for the treatment of severe COVID-19.
ABSTRACT
Background: Opportunistic and chronic infections can arise in the context of treatment used for Autoimmune Rheumatic Diseases (ARDs). Although it is recognized that screening procedures and prophylactic measures must be followed, clinical practice is largely heterogeneous, with relevant recommendations not currently developed or disparately located across the literature. Objectives: To conduct a systematic literature review (SLR) focusing on the screening and prophylaxis of opportunistic and chronic infections in ARDs. This is preparatory work done by members of the respective EULAR task force (TF). Methods: Following the EULAR standardised operating procedures, we conducted an SLR with the following 5 search domains;1) Infection: infectious agents identifed by a scoping review and expert opinion (TF members), 2) Rheumatic Diseases: all ARDs, 3) Immunosuppression: all immunosuppressives/immunomodulators used in rheumatology, 4) Screening: general and specifc (e.g mantoux test) terms, 5) Prophylaxis: general and specifc (e.g trimethop-rim) terms. Articles were retrieved having the terms from domains 1 AND 2 AND 3, plus terms from domains 4 OR 5. Databases searched: Pubmed, Embase, Cochrane. Exclusion criteria: post-operative infections, pediatric ARDs, not ARDs (e.g septic arthritis), not concerning screening or prophylaxis, Covid-19 studies, articles concerning vaccinations and non-Εnglish literature. Quality of studies included was assessed as follows: Newcastle Ottawa scale for non-randomized controlled trials (RCTs), RoB-Cochrane tool for RCTs, AMSTAR2 for SLRs. Results: 5641 studies were initially retrieved (Figure 1). After title and screening and removal of duplicates, 568 full-text articles were assessed for eligibility. Finally, 293 articles were included in the SLR. Most studies were of medium quality. Reasons for exclusion are shown in Figure 1. Results categorized as per type of microbe, are as follows: For Tuberculosis;evidence suggests that tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic DMARDs (csDMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. Conversion of TST/IGRA occurs in about 10-15% of patients treated with biologic DMARDs (bDMARDs). Various prophylactic schemes have been used for latent TB, including isoniazide for 9 months, rifampicin for 4 months, isoniazide/rifampicin for 3-4 months. For hepatitis B (HBV): there is evidence that risk of reactivation is increased in patients positive for hepatitis B surface antigen. These patients should be referred for HBV treatment. Patients who are positive for anti-HBcore antibodies, are at low risk for reactivation when treated with glucocorticoids, cDMARDs and bDMARDs but should be monitored periodically with liver function tests and HBV-viral load. Patients treated with rituximab display higher risk for HBV reactivation especially when anti-HBs titers are low. Risk for reactivation in hepatitis C RNA positive patients, treated with bDMARDs is low. However, all patients should be referred for antiviral treatment and monitored periodically. For pneumocystis jirovecii: prophylaxis with trimeth-oprim/sulfamethoxazole (alternatively with atovaquone or pentamidine) should be considered in patients treated with prednisolone: 15-30mg/day for more than 4 weeks. Few data exist for screening and prophylaxis from viruses like E B V, CMV and Varicella Zoster Virus. Expert opinion supports the screening of rare bugs like histoplasma and trypanosoma in patients considered to be at high risk (e.g living in endemic areas). Conclusion: The risk of chronic and opportunistic infections should be considered in all patients prior to treatment with immunosuppressives/immunomod-ulators. Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics. Collaboration between different disciplines is important.
ABSTRACT
Background/Aims The impact of dealing with COVID-19 for rheumatology higher specialist trainees has been profound. Sacrifices were made to their training to support the UK's pandemic response. Virtual Reality (VR) has long been used as a solution for specific surgical skills;providing a hands-on experience to enable specific delivery of outcomes. We utilised existing technology alongside a specialist VR and haptics team to review ways at delivering a valid and reliable training tool to administer joint injections, beginning with the review of this procedure specific to the knee. We aimed to describe this process. Methods A qualitative study using focus groups was undertaken, one medical student, four higher specialty trainees and two consultants were convened in a focus group to review existing mannequin-based training with the purpose of identifying a skill to develop in virtual reality. A story board was developed through collaboration with a graphic designer. The scenario was imbedded into a virtual reality environment in collaboration with a virtual reality partner. Results The focus group identified intra-articular knee injection as the most appropriate rheumatology skill to develop. Storyboarding built a series of scenarios around clinical situations which would require injection or aspiration. Working with the engineering team we successfully mapped knee joint anatomy and rendered an authentic clinical environment for the storyboards to run inside. Conclusion Virtual reality training scenarios are complex to develop but have enormous potential to create immersive training and assessment experiences which are not boundaried by the challenges of social distancing and COVID-19 risks.
ABSTRACT
Background/Aims Sarcoidosis is a multi-system inflammatory disorder, characterised by the formation of non-caseating granulomas. In the UK, a decision was made to include sarcoid patients in the clinically extremely vulnerable group, and they were advised to shield during the COVID-19 pandemic. We investigated the incidence of covid-19 infection and uptake of COVID-19 vaccine within this patient group. Methods Consecutive patients attending the King's College Hospital sarcoidosis clinic over 18 months between 1st January 2018 and 31st August 2020, and were still alive on 31st January 2020, were included in this report. Electronic primary care records and hospital records were reviewed for each patient to evaluate the incidence of RT-PCT confirmed covid-19 infection, hospitalisation, and vaccination status, defined as at least one vaccination. Hospitalisation data was available from four South-East London trusts. Results The King's College Hospital database identified 416 patients with biopsy confirmed sarcoidosis. Of the complete cohort, the median age was 55.7 years, 193 patients (46%) were male, and 178 patients (43%) were of black ethnicity. A proportion of patients were taking prednisolone (n=116, 28%) and DMARDs (n=73, 18%). The incidence of RT-PCR confirmed covid-19 infection was 48/416 patients (12%). Of these infections, 16/48 (33%) were prior to vaccine availability, including one patient who required an intensive care admission. Post vaccine availability, 9/32 infections were in vaccinated individuals, 8/32 in unvaccinated and 15/32 were of unknown timing;there were 2 recorded hospital admissions but no intensive care admissions, neither patient was immunosuppressed and one was unvaccinated. Uptake of at least one covid-19 vaccine was 287/416 patients (69%). Of the cohort who opted not to have a vaccine (n=129), the median age was 53.7 years, 60 patients (47%) were male, 58 (45%) were black ethnicity and 22 (17%) were white ethnicity. The only demographic variable to predict covid-19 vaccine uptake was ethnicity;patients of black ethnicity were less likely to have the vaccine than those of white ethnicity (OR=0.56, p=0.041). In vaccinated individuals, there were 9/287 cases (3%) of RT-PCT confirmed covid- 19 infection, of which one patient required hospitalisation but not intensive care. Conclusion The incidence of covid-19 infection in our cohort is comparable to that of London (12%), despite an extremely clinically vulnerable population. Vaccine uptake was lower in sarcoid patients (69%) than the national comparator in adults (90%) and was especially low in the black ethnic population.
ABSTRACT
Background/Aims Patients with inflammatory arthritis were identified as a potentially vulnerable group during the COVID-19 pandemic, with recommendations from the UK government to shield. We set out to describe the risks of COVID-19 according to initial treatment strategy amongst patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods NEIAA is an observational cohort design. It includes adults in England with a new diagnosis of inflammatory arthritis between May 2018 and March 2021. The outcomes of interest were death due to COVID-19 (COVID-19 stated on a death certificate) and hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition), identified using NHS Digital linkage. Cox proportional hazards models were used to calculate hazard ratios, with adjustment for patient factors (age, gender, smoking status, comorbidity) and disease factors (seropositivity, disease severity (DAS28), patient-reported disability (HAQ) and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from February 2020 or date of diagnosis (whichever was later) and censored at a COVID-19 event, May 2021 or death (whichever was sooner). Results 14,127 patients were included. Mean age was 57 (+/-16);62% were female. Smoking status: 19% current;29% ex-smokers. Comorbidities: 19% hypertension;9% diabetes;and 9% lung disease. Overall, 20% had two or more comorbidities. Rheumatoid Factor or CCP antibodies were positive in 56%. At presentation, mean scores were 4.6 (+/-1.5) for DAS28, 1.1 (+/-0.7) for HAQ and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients;methotrexate was most common (54%), then hydroxychloroquine (23%) and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 (95% CI: 0.79-1.10) and death: 0.31 (95% CI: 0.23-0.41). Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 events. Higher baseline DAS28 predicted COVID-19 admission (HR 1.24 (95% CI: 1.10-1.39)) and mortality (HR 1.33 (95% CI: 1.09-1.63)). Higher HAQ predicted both COVID-19 admission and death. Seropositivity was not a significant predictor of any COVID- 19 event, nor was MSK-HQ. Unadjusted, corticosteroids associated with COVID-19 death (HR 2.29 (95% CI: 1.02-5.13)), and sulfasalazine monotherapy associated with COVID-19 admission (HR 1.93 (95% CI: 1.04-3.56)). In adjusted models, associations for corticosteroids and sulfasalazine were no longer significant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic. Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.
ABSTRACT
Individuals on immunosuppression were excluded from COVID-19 vaccine trials. We evaluated immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in people taking methotrexate and biologics. Given the roll out of extended interval vaccination programmes to maximise population coverage, we present findings following the first dose. We recruited individuals with psoriasis (n=84) established on methotrexate or biologic monotherapy (TNF, IL-17 or IL-23 inhibitors) and healthy controls (n=17). Immunogenicity was evaluated pre and post (day 28) vaccine. Seroconversion rates were lower in patients taking immunosuppression (78%, 95%CI 67-87%) compared to controls (100%, 95%CI 79-100%), with the lowest rate in those on methotrexate (50%, 95%CI 26-74%). Neutralising activity to wild-type SARS-CoV-2 was lower in patients receiving methotrexate (median ID50 152, IQR 47-257) compared to controls (median ID50 316, IQR 212-481, p<0.01), but preserved in those receiving biologics (median ID50 280, IQR 137-428). Neutralising titres against B.1.1.7 were comparably low in all participants. Spike-specific T cell responses (including IFNγ, IL-2, IL-21) were induced in all groups, and were equivalent among individuals receiving methotrexate, biologics and controls. Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by biologics, while cellular responses are unaffected. Seroconversion alone may not adequately reflect vaccine immunogenicity in individuals with immune-mediated disease receiving immunosuppression. Real-world pharmacovigilance studies will determine whether these findings translate to clinical effectiveness.
ABSTRACT
OBJECTIVES: Myalgia is a widely publicised feature of Covid-19, but severe muscle injury can occur. This systematic review summarises relevant evidence for skeletal muscle involvement in Covid-19. METHODS: A systematic search of OVID and Medline databases was conducted on 16/3/2021 and updated on 28/10/2021 to identify case reports or observational studies relating to skeletal muscle manifestations of Covid-19 (PROSPERO: CRD42020198637). Data from rhabdomyolysis case reports were combined and summary descriptive statistics calculated. Data relating to other manifestations were analysed for narrative review. RESULTS: 1920 articles were identified. From these, 61 case reports/series met inclusion criteria, covering 86 rhabdomyolysis cases. Median age of rhabdomyolysis patients was 50 years, (range 6-89). 49% had either hypertension, diabetes mellitus or obesity. 77% were male. Symptoms included myalgia (74%), fever (69%), cough (59%), dyspnoea (68%). Median peak CK was 15,783U/L. 28% required intravenous haemofiltration and 36% underwent mechanical ventilation. 62% recovered to discharge and 30% died. Dyspnoea, elevated CRP and need for intravenous haemofiltration increased risk of fatal outcome. Additional articles relating to skeletal muscular pathologies include 6 possible concomitant diagnoses or relapses of idiopathic inflammatory myopathies and 10 reports of viral-induced muscle injuries without rhabdomyolysis. Localised myositis and rhabdomyolysis with SARS-CoV-2 vaccination have been reported. CONCLUSIONS: Rhabdomyolysis is an infrequent but important complication of Covid-19. Increased mortality was associated with a high CRP, renal replacement therapy and dyspnoea. The idiopathic inflammatory myopathies (IIM) may have viral environmental triggers. However, to date the limited number of case reports do not confirm an association with Covid-19.
ABSTRACT
Case report-IntroductionBacterial and fungal infections are recognised complications of viral pneumonia, particularly in patients who are critically ill. We describe a case of fungal sacroiliitis complicating severe COVID-19 pneumonia following a prolonged intensive care unit (ICU) admission.Candida albicans sacroilitis is a rarely reported infection with few case reports in the literature. Candida osteoarticular infections can present as septic arthritis, with knee involvement in 75% of cases, or osteomyelitis. The latter presentation differs based on age-vertebral involvement (51%) is more common in adults while children are more likely to present with infection in the long bones, ribs, or sternum.Case report-Case descriptionA 48-year-old Afro-Caribbean gentleman with a history of hypertension and obesity was admitted to the ICU with clinical, laboratory and radiographic features of COVID-19 infection despite persistently negative swabs. Whilst in ICU he required mechanical ventilation. His stay was further complicated by multiple infections, pulmonary emboli, and the presence of a cavitating lesion in the left lung. Cultures from bronchoalveolar lavage and a central venous catheter line grew Serratia Mascense, candida glabrata and pseudomonas were isolated from his urine. He was treated with multiple antibiotics including meropenem, tazocin, ceftazidime and avibactam.After 61 days in the ICU he was transferred to the ward. He developed severe pain in his right hip which was worse on movement. This was followed by urinary incontinence and sensory deficit in the right L2/L3 dermatome. He underwent magnetic resonance imaging (MRI) of his spine and sacroiliac joints which showed right sided sacroiliitis and oedema around the iliopsoas muscle. He was started on vancomycin, later changed to ceftazidime avibactam and metronidazole. An echocardiogram did not show any vegetations. He underwent a biopsy of his sacroiliac joints which confirmed the presence of leucocytes, extended cultures yielded candida albicans in one out of two biopsy specimens.Considering ongoing pyrexia, pain and inflammatory markers, intravenous fluconazole was added to his antibiotic regimen which resulted in a marked improvement in mobility. After four weeks, ceftazidime, metronidazole and avibactam were stopped, and fluconazole was administered as oral tablets. 6 days later he became febrile and IV fluconazole was restarted.A repeat chest CT showed resolution of the cavity but ongoing changes suggestive of organising pneumonia. A repeat MRI of the sacroiliac joints revealed minor improvement. Intravenous Fluconazole was continued for a total of 8 weeks and was changed to tablets for complete a total of 12 weeks.Case report-DiscussionThis is a severe case of COVID-19 infection who despite 9 negative PCR tests, on day 53, had positive IgG for SARS-CoV-2 infection, confirming our clinical suspicion. Particularly in the ICU setting, individuals are approximately ten times more likely to have secondary bacterial/fungal infections with more frequent detection of multidrug-resistant Gram-negative pathogens.This case highlights several difficulties. Urine cultures had confirmed candida albicans, likely to be related to catheter related urinary tract infections, and a possible source for our patient but also a resistant pseudomonas aeruginosa species. Furthermore, cultures were positive for Serratia Mascense, candida glabrata. He had also already been treated with prolonged, broad spectrum antimicrobial treatment. Considering this, establishing the aetiology of the septic sacroiliitis was challenging. The rarity of candida sacroiliitis and presence of the organism in just one specimen made this more difficult. This led to the decision of a repeat sacroiliac biopsy to supply sufficient samples for further microbial analyses such as 16S, 18S and mycobacteria culture, all of which were negative.He became febrile after the discontinuation of antimicrobials and a switch to oral fluconazole therapy. He was extensively re-investigated and despite resolution of t e lung cavity, there were changes which could have been consistent with an organising pneumonia. At this point he was neutropenic, mildly eosinophilic, and therefore a drug reaction was also considered.Repeat MRI revealed resolving muscle inflammation and minimal change at the bone site, with erosions and possible reactive bone marrow oedema. Following discussion with microbiology the decision was made to persist with intravenous Fluconazole. He continued to improve, and his inflammatory markers normalised after 8 weeks of treatment. Prednisolone was started for COVID-19 related pneumonitis. Long-term antifungal treatment is advisable, and we aim to complete 12 weeks of treatment.Case report-Key learning points Patients with SARS-CoV-2 infection, particularly those requiring ICU admission were at risk of developing superinfections with multidrug-resistant Gram-negative bacteria or fungal infections.Candida albicans sacroiliitis is rare therefore early aspiration/biopsy is essential for the management.Longer treatment is needed in osteoarticular candida infections, even up to 6 or 12 months, therefor long-term close monitoring of this patients is essential.The utility and timing of reimaging patients following such infections is still unclearClose multidisciplinary and interdisciplinary team collaboration is essential in the management of this complex patients.
ABSTRACT
P135 Table 1Patient demographics, self-reported scores and functional test results by wave 1st wave 2nd wave p-value Demographics n=167 n=141 Age 59±13 58±12 0.564 Female 60 (35.93;28.94–43.40) 62 (43.97;35.97–52.22) 0.15 BMI (kg/m2) 30.5 (26.6–35.2) 32.1 (28.5–37.9) 0.009 ** BAME 115 (69.7;62.39–76.32) 72 (59.5;50.62–67.94) 0.073 Number of comorbidities 2 (1–3) 2 (1–3) 0.144 Patients Receiving Drugs Dexamethasone 11 (6.63;3.57–11.17) 138 (97.87;94.43–99.40) <0.001 *** Remdesivir 18 (10.84;6.79–16.24) 81 (57.45;49.20–65.39) <0.001 *** Other Immunomodulator 2 (1.20;0.25–3.81) 31 (21.99;15.76–29.35) <0.001 *** Questionnaire Scores n=164 n=132 NRS Breathlessness 2 (0–5) 3 (0–5) 0.153 ≥4 56 (34.78;27.75–42.36) 52 (37.14;29.47–45.34) 0.67 NRS Cough 0 (0–2) 0 (0–3) 0.439 ≥4 17 (10.56;6.52–16.00) 18 (13.64;8.59–20.26) 0.419 NRS Fatigue 3 (0–5) 3 (0–5) 0.867 ≥4 65 (40.63;33.24–48.35) 48 (36.92;28.99–45.43) 0.52 NRS Pain 0 (0–5) 1 (0–3) 0.682 ≥4 44 (27.50;21.03–34.78) 30 (23.08;16.48–30.86) 0.39 NRS Sleep disturbance 2 (0–5) 2 (0–5) 0.558 ≥4 52 (32.50;25.61–40.02) 49 (37.40;29.47–45.89) 0.382 Pre-COVID-19 mMRC 1 (0–2) 1 (1–2) 0.478 Post-COVID-19 mMRC 0 (0–1) 0 (0–1) 0.329 Post-COVID-19 mMRC ≥2 66 (40.99;33.61–48.70) 49 (38.58;30.45–47.23) 0.678 PCFS 2 (0–3) 1 (0–2) 0.055 PCFS ≥2 80 (50.00;42.31–57.69) 51 (42.15;33.62–51.05) 0.191 PHQ-9 ≥10 32 (20.38;14.66–27.19) 29 (23.02;16.33–30.92) 0.592 GAD-7 ≥10 34 (21.38;15.56–28.24) 16 (12.80;7.81- 19.49) 0.059 TSQ ≥6 43 (27.56;21.01–34.94) 27 (22.31;15.60–30.33) 0.319 Functional Tests n=160 n=139 4MGS <0.8 (ms-1) 67 (42.41;34.89–50.19) 47 (35.07;27.38–43.40) 0.201 1STS repetitions 18 (12–23) 17 (12–21) 0.460 <2.5 percentile 96 (60.00;52.29–67.36) 108 (77.70;70.25–84.00) 0.011 * Desaturation ≥4% 52 (34.67;27.40–4 .52) 42 (32.31;24.73–40.67) 0.677 Parametric data are presented as mean ± standard deviation, non-parametric data are presented as median (interquartile range) or frequency (proportion;95% confidence interval). Statistical significance indicated by * (p<0.05), ** (p<0.01), *** (p<0.001). BMI = Body mass index, BAME = Black, Asian or minority ethnic, NRS = Numerical rating scale (0–10), mMRC = modified Medical Research Council for dyspnoea (0–4), PCFS = Post-COVID-19 functional status scale (0–4), PHQ-9 = Patient health questionnaire 9 (0–27), GAD-7 = General Anxiety Disorder-7 scale (0–21), TSQ = Trauma screening questionnaire (0–10), 4MGS = 4-metre gait speed, 1STS = 1-minute sit-to-stand.ConclusionDespite shorter admission duration, and less frequent IMV, the burden of symptoms and functional limitation experienced post-hospitalisation for severe COVID-19 pneumonia was at least as severe during Wave 2 as in Wave 1. Identification of contributing factors and impact on post-COVID rehabilitation outcomes requires further study.
ABSTRACT
Background: Hydroxychloroquine (HCQ) has attracted much attention especially during the COVID-19 pandemic. HCQ and closely related chloroquine (CQ) have known ocular and cardiac toxicity. However, although screening guidance now exists from the Royal College of Ophthalmologists for the former (RCOphth)1, little is known regarding predictors of both forms of toxicity. Objectives: To systematically explore the literature on predictors of toxicity limited to cardiac and ocular toxicity. Methods: A detailed search of the following databases was conducted: PubMed, Medline, Embase, Web of Science, The Cochrane library, EMCare and Academic Search Premier. Studies addressing predictors of HCQ toxicity with relevant search terms used were included. Exclusion criteria were: non-English articles, pre-clinical and paediatric studies. Three authors (SR, NC, PK) independently screened titles and abstracts for inclusion, ensuring each article was screened twice. Disagreement over inclusion was adjudicated by senior reviewers (EN, JG). Data extraction (SR, NC, PK) focused on predictors of toxicity. Results: The search strategy retrieved 3103 studies. 147 studies were included for data extraction, of which 92 were eventually excluded due to: not identifying predictors (n=17), reviews (n=19), not ocular or cardiovascular toxicity (n=18), case reports (n=3), paediatrics (n=1), screening articles that focused on detecting retinopathy (n=30), article unobtainable at time of abstract submission (n=4), leaving 55 studies for full review. Studies addressing cardiac toxicity (n=16) included: cohort, retrospective observational, a comparative pharmacovigilance, systematic monitoring protocol and a randomised control trial (RCT). The majority of these involved high-dose (>5mg/ kg/day) use for acute COVID-19 infection. The main significant predictors identified were: Hydroxychloroquine (HCQ) use in combination with azithromycin (6/7 studies), cumulative dose (2 studies), pre-existing cardiovascular morbidity (2/3 studies) and prolonged baseline QTc (2 studies). Individual associations were also identified in the following: longer treatment duration, daily dosage, increased age, male gender, severe COVID-19 infection, abnormal liver function tests (LFTs) and concurrent use of loop-diuretics. Regarding predictors of ocular toxicity (n=39), only one study was a RCT. The remainder were observational studies: case-control, cohort, retrospective chart reviews and letters to the editor which included original patient data. Several predictors of retinopathy and maculopathy were examined in two or more studies and included: duration of use (16/18 studies), daily dosage (7/13 studies), cumulative dose (11/14 studies), increased age (10/11 studies), body weight or BMI (3/5 studies), renal impairment (5 studies), HCQ blood levels (2 studies), keratopathy (2 studies) and tamoxifen use (2 studies). Sex (2 studies) and history of cataract surgery (2 studies) were not found to be predictors of toxicity. Only few studies performed regression analysis presenting odds and/or hazard ratios with confidence intervals. Conclusion: The most recognised predictor of cardiac toxicity was co-administration with azithromycin. In ocular toxicity, commonly cited predictors included those already recognised by the RCOphth1, as well as cumulative dose, increased age, weight considerations, HCQ blood levels and keratopathy. Further research is warranted on better characterising predictors of cardiac and ocular toxicity in patients on HCQ and CQ therapy.