AUTOANTIBODIES RELATED TO RHEUMATIC DISEASES AFTER COVID-19 INFECTION

BackgroundSARS-CoV-2(Severe acute respiratory syndrome coronavirus 2) has been circulating worldwide for three years. It mainly causes upper respiratory tract infection, which can manifest as pulmonary infection and even respiratory distress syndrome in severe cases. Different autoantibodies can be detected in patients infected with COVID-19.ObjectivesTo explore autoantibodies related to rheumatic diseases after COVID-19 infection.MethodsNinety-eight inpatients were tested for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens(ENA), anti-neutrophil cytoplasmic antibodies（ANCA), anticardiolipin antibodies,a-β2GPI (IgG/IgM). They were from a tertiary hospital in Guangzhou during the COVID-19 epidemic. Data were described statistically.ResultsNinety-eight hospitalized patients were tested for relevant antibodies. The average age was 50.64±19.54;67 (68.4%) were male, 64 (65.3%) were COVID-19 positive, 90 (90.9%) had rheumatic diseases, and 56 of them were COVID-19 positive patients with rheumatic diseases.There were 76 patients tested for antinuclear antibodies;29 （38.16%）were negative, 18 （23.68%）had a 1/80 titre, and 29（28.16%） had a titre greater than 1:80. The 31 covid patients were positive for ANA. In the high-titer group, 19 patients with rheumatic diseases were positive for COVID-19, and 12 patients had an exacerbation of the rheumatic diseases (6 of whom had previously had pulmonary fibrosis). Of 31 covid patients, only two were non-rheumatic patients, and both were elderly, aged 85 and 100, respectively.Fifty-six patients had ENA results, and 29 for positive antibodies, 8 for ds-DNA antibodies, 2 for anti-Sm antibodies, 6 for anti-nucleosome antibodies, 12 for anti-U1RNP antibodies, 2 for anti-Scl-70 antibodies, 12 for anti-SS-A antibodies, 3 for anti-mitochondrial M2 antibodies, 2 for anti-centromere antibodies, 1 for anti-Po antibodies, and one for anti-Jo-1 antibody. All 56 patients had rheumatic diseases, and no new patients were found.There were 62 patients with ANCA data. P-ANCA was positive in 12 cases(19.35%), and MPO-ANCA was positive in 2 cases. An 85-year-old non-rheumatic COVID-19 patient was P-ANCA positive. She had a history of hypertension, colon cancer, CKD3, coronary heart disease, and atrial flutter.In the anticardiolipin antibodies group, there were 62 patients;only 6 were positive, and 2 were rheumatic patients infected with COVID-19. Antiphospholipid antibodies were detected in 33 patients, and a-β2GPI was tested in one patient, an 82-year-old COVID-19 patient with gout, diabetes, and cerebral infarction in the past. We did not find a statistical difference in the above results.ConclusionWe have not found a correlation between SARS-CoV-2 and serum autoantibodies of rheumatic immune diseases. It needs large samples and an extended follow-up to research.AcknowledgementsThis work was supported by Scientific and Technological Planning Project of Guangzhou City [202102020150], Guangdong Provincial Basic and Applied Basic Research Fund Project [2021A1515111172], National Natural Science Foundation of China Youth Fund [82201998] and Third Affiliated Hospital of Sun Yat-Sen University Cultivating Special Fund Project for National Natural Science Foundation of China [2022GZRPYQN01].Disclosure of Interestsone declared.

THE PREVALENCE AND INCIDENCE OF PSORIASIS AND PSORIATIC ARTHRITIS IN ENGLAND FROM 2009-2019: AN OBSERVATIONAL STUDY USING PRIMARY CARE DATA

BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) can greatly impact quality of life and result in substantial personal and societal costs. Complete and up to date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated.ObjectivesTo determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England.MethodsWe used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies to ensure inclusion of all relevant codes. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results.ResultsThe prevalence of PsO and PsA in males and females increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42];PsO females 2.60% [95% CI 2.59-2.61];PsA males 0.20% [95% CI 0.20-0.20];PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group;PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 (164-171) in 2009 to 148 (145-151) in 2019) but in females it has been stable with a slight annual decrease (from 180 (177-184) in 2009 to 173 (170-176) in 2019). The annual incidence for PsA has increased in both males and females (13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females).ConclusionThe increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population.ReferencesNIL.Table 1.Prevalence of PsO and PsA from 2009-2019 in EnglandYear20092010201120122013201420152016201720182019Population (n)1073383110910802110318501118036711343299112249341137842211657996119336261223432512420998PsO (n)216841229106239819250667259988268032276804286499295712304568311104PsO prevalence (%, 95%CI)-Male1.98 (1.96-1.99)2.06 (2.05- 2.07)2.13 (2.12-2.14)2.19 (2.18-2.20)2.24 (2.23- 2.25)2.33 (2.32- 2.34)2.37 (2.36- 2.38)2.39 (2.38- 2.40)2.40 (2.39- 2.41)2.40 (2.39- 2.42)2.41 (2.40- 2.42)-Female2.07 (2.05- 2.08)2.14 (2.13- 2.16)2.22 (2.21- 2.23)2.29 (2.28- 2.31)2.35 (2.33- 2.36)2.45 (2.43- 2.46)2.50 (2.49- 2.51)2.53 (2.52- 2.54)2.56 (2.54- 2.57)2.58 (2.56- 2.59)2.60 (2.59- 2.61)PsO incidence (100,000 person years)-Male168 (164-171)158 (155- 162)161 (158-165)153 (150-157)161 (157- 164)156 (153- 159)155 (152- 159)154 (151- 157)153 (150-156)150 (147-153)148 (145-151)-Female180 (177-184)176 (172-179)181 (177-184)171 (167-174)175 (171-178)176 (172-180)179 (176-183)178 (174-181)177 (174-181)174 (170-177)173 (170-176)PsA (n)1444515443164681752218545196182072021994232572451425683PsA prevalence (%, 95%CI)-Male0.14 (0.14- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.16- 0.17)0.18 (0.17- 0.18)0.18 (0.18- 0.19)0.19 (0.18- 0.19)0.19 (0.19- 0.20)0.20 (0.19- 0.20)0.20 (0.20- 0.20)-Female0.13 (0.13- 0.13)0.14 (0.13- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.17- 0.18)0.18 (0.18- 0.18)0.19 (0.19- 0.19)0.20 (0.19- 0.20)0.20 (0.20- 0.21)0.21 (0.21- 0.22)PsA incidence (100,000 person years)-Male13 (12- 14)12 (11- 13)13 (12- 14)12 (11- 13)13 (12-14)14 (13- 15)14 (13- 15)14 (13-15)1514-16)14(13- 15)15 (14-16)-Female12 (11- 13)13 (12- 14)13 (12- 14)14 (13-15)14 (13-15)15 (14-16)17 (16- 18)16 (15- 17)17 (16- 18)18 (17-19)18 (17-19)Acknowledgements:NIL.Disclosure of InterestsArani Vivekanantham: None declared, Edward Burn: None dec ared, Marta Pineda-Moncusí: None declared, Sara Khalid Grant/research support from: SK has received research grant funding from the UKRI and Alan Turing Institute outside this work. SK's research group has received grant support from Amgen and UCB Biopharma., Daniel Prieto-Alhambra Grant/research support from: DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department., Laura Coates Speakers bureau: LC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB., Consultant of: LC has worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB., Grant/research support from: LC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer.

SAFETY OUTCOMES IN PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH FILGOTINIB (FIL) IN FILOSOPHY: INTERIM RESULTS FROM A PROSPECTIVE OBSERVATIONAL STUDY

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.

COVID-19 IN PATIENTS WITH RHEUMATIC IMMUNE-MEDIATED INFLAMMATORY DISEASES IN AMERICA: DIFFERENCES AND SIMILARITIES BETWEEN MEXICO AND ARGENTINA

BackgroundPatients with immune-mediated rheumatic diseases (IRD) have poorer outcomes of SARS-CoV-2 infection compared to the general population.ObjectivesTo assess and compare clinical course, severity and complications of SARS-CoV-2 infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Mexico and Argentina.MethodsData from both national registries, CMR-COVID (Mexico) and SAR-COVID (Argentina), were combined. Briefly, adult IRD patients with SARS-CoV-2 infection were recruited between 08.2020 and 09.2022 in SAR-COVID and between 04.2020 and 06.2022 in CMR-COVID. Sociodemographic data, comorbidities, and DMARDs were recorded, as well as clinical characteristics, complications, and treatment for SARS-CoV-2 infection. Descriptive analysis. Chi square, Fisher, Student T, Mann Whitney U tests and multiple logistic regression analyses were performed.ResultsA total of 3709 patients were included, 1167 (31.5%) from the CMR-COVID registry and 2542 (68.5%) from the SAR-COVID registry. The majority (82.3%) were women, with a mean age of 50.4 years (SD 14.4). The most frequent IRD were rheumatoid arthritis (47.5%) and systemic lupus erythematosus (18.9%). Mexican patients were significantly older, had a higher female predominance and had higher prevalence of rheumatoid arthritis, antiphospholipid syndrome, and axial spondyloarthritis, while the Argentine patients had more frequently psoriatic arthritis and ANCA-associated vasculitis. In both cohorts, approximately 80% were in remission or low disease activity at the time of infection. Mexicans took glucocorticoids (43% vs 37%, p<0.001) and rituximab (6% vs 3%, p<0.001) more frequently. They also reported more comorbidities (48% vs 43%, p=0.012).More than 90% of patients presented symptoms related to SARS-CoV-2 infection. The frequency of hospitalization was comparable between the groups (23.4%), however, the Mexicans had more severe disease (Figure 1) and a higher mortality rate (9.4% vs 4.0%, p<0.0001). After adjusting for risk factors, Mexicans were more likely to die due to COVID-19 (OR 2.2, 95%CI 1.5-3.1).ConclusionIn this cohort of patients with IRD from Mexico and Argentina with SARS-CoV-2 infection, the majority presented symptoms, a quarter were hospitalized and 6% died due to COVID-19. Mexicans presented more severe disease, and after considering risk factors they were two times more likely to die.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsCarolina Ayelen Isnardi Grant/research support from: SAR-COVID is a multi- sponsor registry, where Pfizer, Abbvie, and Elea Phoenix provided unrestricted grants. None of them participated or infuenced the development of the project, data collection, analysis, interpretation, or writing the report. They do not have access to the information collected in the database, Deshire Alpizar-Rodriguez: None declared, Marco Ulises Martínez-Martínez: None declared, Rosana Quintana: None declared, Ingrid Eleonora Petkovic: None declared, Sofia Ornella: None declared, Vanessa Viviana Castro Coello: None declared, Edson Velozo: None declared, David Zelaya: None declared, María Severina: None declared, Adriana Karina Cogo: None declared, Romina Nieto: None declared, Dora Aida Pereira: None declared, Iris Jazmin Colunga-Pedraza: None declared, Fedra Irazoque-Palazuelos: None declared, GRETA CRISTINA REYES CORDERO: None declared, Tatiana Sofía Rodriguez-Reyne: None declared, JOSE ANTONIO VELOZ ARANDA: None declared, Cassandra Michele Skinner Taylor: None declared, INGRID MARIBEL JUAREZ MORA: None declared, Beatriz Elena Zazueta Montiel: None declared, Atzintli Martínez: None declared, Cesar Francisco Pacheco Tena: None declared, Guillermo Pons-Estel: None declared.

HIGH DOSE INTRAVENOUS ANAKINRA TREATMENT IS SAFE AND EFFECTIVE IN SEVERE AND CRITICAL COVID-19 PATIENTS: A PROPENSITY SCORE MATCHED STUDY IN A SINGLE CENTER

BackgroundIn COVID-19 severe disease course such as need of intensive care unit (ICU) as well as development of mortality is mainly due to cytokine storm.ObjectivesIn this study, we aimed to evaluate the high dose intravenous anakinra treatment response and outcome in patients with severe and critical COVID-19 compared to standard of care.MethodsThis retrospective observational study was carried out at a tertiary referral center. The study population consisted of two groups as follows;the patients receiving high dose intravenous anakinra (anakinra group) between 01.09.2021 and 01.02.2022 and the patients treated with standard of care (SoC, control group) as historical control group who were hospitalized between 01.07.2021 and 01.09.2021.ResultsAfter the propensity score 1:1 matching 79 patients in anakinra and 79 patients in SoC matched and included into the analysis. Mean±SD patient age was 67.4±16.7 and 67.1±16.3 years in anakinra and SoC group, respectively (p=0.9). Male gender was 38 (48.7 %) in anakinra and 36 (46.2 %) SoC (p=0.8). Overall, ICU admission was in 14.1 % (n=11) and 30.8 % (n=24) (p=0.013;OR: 6.2), intubation in 12.8 % (n=10) and 16.7 % (n=13) patients (p=0.5), 14.1 % (n=11) and 32.1 % (n=25) patients died in anakinra and control group, respectively (p=0.008;OR: 7.1)ConclusionIn our study mortality was lower in patients receiving anakinra compared to SoC. Intravenous high dose anakinra is safe and effective treatment in patients with severe and critical COVID-19.Table 1.Baseline clinical and laboratory features of patients receiving standard of care (SoC) and Anakinra before and after propensity score (PS) matchingBefore PS matchingAfter PS matchingVariablesAnakinra (n=148)SoC (n=114)p value (OR)Anakinra (n=78)SoC (n=78)p value (OR)Age (years) (mean±SD)66.8±1763.1±170.0967.4±16.767.1±16.30.9Gender, male (n, %)78 (52.7)45 (39.5)0.033 (4.5)38 (48.7)36 (46.2)0.8Duration of hospitalization (days) (median, IQR)11 (12)9 (7.3)0.027.5 (9)11 (8)0.01Comorbidities (n, %) Diabetes mellitus41/146 (28.1)39 (34.2)0.318 (23)31 (39.7)0.025 (5) Hypertension84/143 (58.7)64 (56)0.730 (61.5)50 (64)0.7 Coronary heart disease27/143 (19)24 (21)0.718 (23)20 (25.6)0.7 Heart failure18/143 (12.6)23 (20)0.114 (18)20 (25.6)0.24 Chronic renal failure31 (21)6 (5.3)<0.001 (13.06)15 (19)6 (7.7)0.035 (4.5) Chronic obstructive lung disease23/144 (16)19 (16.7)0.914 (18)15 (19)0.8 Dementia15/117 (12.8)2 (1.8)0.001 (10.4)3/61 (5)2 (2.6)0.5 Malignancy16/146 (11)8 (7)0.39 (11.5)6 (7.7)0.4 Immunosuppressive usage18/146 (12.3)2 (1.8)0.001 (10.08)5 (6.5)2 (2.6)0.2Disease severity (n, %) NIH score 3 (severe)57 (38.5)68 (59.6)0.001 (11.5)48 (61.5)44 (56.4)0.5 NIH score 4 (critical)91 (61.5)46 (40.4)30 (38.5)34 (43.6) mcHIS score (mean±SD)3.4±1.22.64±1.5<0.0012.9±13.1±1.30.2PS: Propensity score, SoC: Standard of care, OR: Odds ratio, SD: Standard deviation, IQR: Interquartile range, mcHIS: Modified Covid hyperinflammatory syndrome score, NIH: National Institute Health, ALT: Alanin aminotransferase, AST: Aspartate aminotransferaseTable 2.Outcomes of patients receiving SoC and Anakinra before and after PS matchingBefore PS matchingAfter PS matchingVariables (n, %)Anakinra (n=148)SoC (n=114)p value (OR)Anakinra (n=78)SoC (n=78)p value (OR)Pneumothorax3/134 (2.2)00.25*2/73 (2.7)00.5*Myocardial infarction3/132 (2.3)6 (5.3)0.32/72 (2.8)2/56 (3.6)1Pulmonary embolism4/134 (3)11 (9.6)0.034 (4.8)*3/73 (4.1)7 (9)0.3*Intensive care unit60 (40.5)25 (22)0.001 (10.2)11 (14.1)24 (30.8)0.013 (6.2)Intubation54 (36.5)13 (11.4)<0.001 (21.3)10 (12.8)13 (16.7)0.5Mortality56 (37.8)27 (23.7)0.015 (5.96)11 (14.1)25 (32.1)0.008 (7.1)PS: Propensity score, SoC: Standard of care, OR: Odds ratioREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Artificial intelligence and machine learning in clinical trial design and application

In 2020, COVID-19 changed how health care was approached both in the United States and globally. In the early phases, the vast majority of energy and attention was devoted to containing the pandemic and treating the infected. Toward the end of 2020, that attention expanded to vaccinating people across the globe. What was not being considered at the time were challenges to future health and clinical trials that power new treatments for COVID-19 and non-COVID-19 treatments. © 2023 Elsevier Inc. All rights reserved.

REVACCINATION OF PATIENTS WITH SLE OR RA WITHOUT AN INITIAL COVID-19 VACCINE RESPONSE ELICITS SEROCONVERSION IN HALF OF THE PATIENTS

BackgroundTreatment with Rituximab (RTX) in patients with rheumatic diseases (RD) has presented a challenge during the COVID-19 pandemic, as RTX leads to markedly reduced and often undetectable antibody responses after COVID-19 vaccination (1).ObjectivesTo investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with RD who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion.MethodsFrom a RD cohort (COPANARD) vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies (abs) and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralizing abs, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. This study was funded by the Danish Rheumatism Association.ResultsPatient demographics are given in Table 1. Forty-seven percent of cases had detectable total SARS-CoV-2 abs and neutralizing abs after revaccination. However, antibody levels were significantly lower than in controls and blood donors (p<0.008), Figure 1A+B. Revaccination induced an antibody class switch in cases with a decrease in detectable IgM abs (Baseline 11/17, Followup 3/17) and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups, Figure 1C. The proportion of cases with detectable CD4+ T cells increased from 69% to 88% (p=0.25), and for CD8+ T cells, the proportion decreased from 88% to 82% (p=1.00). Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors, Figure 1D. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination, Figure 1D.Univariate logistic regression analysis was performed to analyze if active RTX treatment, the presence of B-cells, or a positive T-cell response prior to revaccination predicted seroconversion of total SARS-CoV-2-abs in the patient cohort. We did not find a significant explanatory effect of either variable in the univariate logistic models, data not shown.Table 1.DemographicsCases Revaccination, n=17Controls Boost, n=29Female sex, no(%)1482%2172%Age, median (IQR)6549 - 706762 - 72Disease duration, years1510 - 18229 - 31Rheumatoid Arthritis/SLE13/410/19None DMARD529%828%Prednisone424%13%Methotrexate741%1241%Hydroxychloroquine212%414%None biologic treatment424%931%Rituximab1271%0TNF-inhibitors16%724%JAK-inhibitors0621%IL-6-inhibitors, Abatacept, Benlysta0724%Previous rituximab treatmentAny rituximab treatment1694%13%RTX within the last 15 months, no1488%0Cumulative total dose, mg134-242Time from RTX to revaccination, months95-1249Figure 1.ConclusionIn conclusion, forty-seven percent of initial non-responders were able to seroconvert after two-dose revaccination. However, plasma concentrations of the antibodies against SARS-COV-2 and the levels of neutralizing capacity remained significantly lower than in immunocompetent blood donors. B-cell levels or T-cell responses before revaccination did not predict seroconversion. Our study suggests that patients with RDs who did not mount a detectable serological response to a COVID-19 mRNA vaccine have a T cell response similar to immunocompetent controls. Future studies should establish the antibody levels that identify RD patients without sufficient protection against SARS-CoV-2 infection.References[1]Troldborg A, et al. Time Since Rituximab Treatment Is Essential for Developing a Humoral Response to COVID-19 mRNA Vaccines in Patients With Rheumatic Diseases. J Rheumatol. 2022.AcknowledgementsThe Danish Rheumatism Association [grant number R203-A7217]. We acknowledge all patients and blood donors contributing to the stud for their invaluable participation. The authors would like to thank Sif Kaas Nielsen and Mads Engelhardt Knudsen, the Laboratory of Molecular Medicine at Rigshospitalet, for their excellent technical assistance in analyzing the samples.Disclosure of InterestsNone Declared.

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.

Health Disparities and Comparison of Psychiatric Medication Use before and after the COVID-19 Pandemic Lockdown among General Practitioner Practices in the North East of England.

BACKGROUND: Psychiatric medications play a vital role in the management of mental health disorders. However, the COVID-19 pandemic and subsequent lockdown limited access to primary care services, leading to an increase in remote assessment and treatment options to maintain social distancing. This study aimed to investigate the impact of the COVID-19 pandemic lockdown on the use of psychiatric medication in primary care settings. METHODS: We conducted a retrospective claims-based analysis of anonymized monthly aggregate practice-level data on anxiolytics and hypnotics use from 322 general practitioner (GP) practices in the North East of England, where health disparities are known to be higher. Participants were all residents who took anxiolytics and hypnotics from primary care facilities for two financial years, from 2019/20 to 2020/21. The primary outcome was the volume of Anxiolytics and Hypnotics used as the standardized, average daily quantities (ADQs) per 1000 patients. Based on the OpenPrescribing database, a random-effect model was applied to quantify the change in the level and trend of anxiolytics and hypnotics use after the UK national lockdown in March 2020. Practice characteristics extracted from the Fingertips data were assessed for their association with a reduction in medication use following the lockdown. RESULTS: This study in the North East of England found that GP practices in higher health disparate regions had a lower workload than those in less health disparate areas, potentially due to disparities in healthcare utilization and socioeconomic status. Patients in the region reported higher levels of satisfaction with healthcare services compared to the England average, but there were differences between patients living in higher versus less health disparate areas. The study highlights the need for targeted interventions to address health disparities, particularly in higher health disparate areas. The study also found that psychiatric medication use was significantly more common in residents living in higher health disparate areas. Daily anxiolytics and hypnotics use decreased by 14 items per 1000 patients between the financial years 2019/20 and 2020/21. A further nine items per 1000 decreased for higher health disparate areas during the UK national lockdown. CONCLUSIONS: People during the COVID-19 lockdown were associated with an increased risk of unmet psychiatric medication demand, especially for higher health disparate areas that had low-socioeconomic status.

Remdesivir Use in the Real-World Setting: An Overview of Available Evidence.

In the years of Coronavirus Disease 2019 (COVID-19), various treatment options have been utilized. COVID-19 continues to circulate in the global population, and the evolution of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has posed significant challenges to the treatment and prevention of infection. Remdesivir (RDV), an anti-viral agent with in vitro efficacy against coronaviruses, is a potent and safe treatment as suggested by a plethora of in vitro and in vivo studies and clinical trials. Emerging real-world data have confirmed its effectiveness, and there are currently datasets evaluating its efficacy and safety against SARS-CoV-2 infections in various clinical scenarios, including some that are not in the SmPC recommendations according for COVID-19 pharmacotherapy. Remdesivir increases the chance of recovery, reduces progression to severe disease, lowers mortality rates, and exhibits beneficial post-hospitalization outcomes, especially when used early in the course of the disease. Strong evidence suggests the expansion of remdesivir use in special populations (e.g., pregnancy, immunosuppression, renal impairment, transplantation, elderly and co-medicated patients) where the benefits of treatment outweigh the risk of adverse effects. In this article, we attempt to overview the available real-world data of remdesivir pharmacotherapy. With the unpredictable course of COVID-19, we need to utilize all available knowledge to bridge the gap between clinical research and clinical practice and be sufficiently prepared for the future.

Outcomes of Sars-Cov-2 Infection in Patients with Anca Associated Vasculitis. Data from the National Sar-Covid Registry

Objectives: To describe the clinical characteristics and outcomes of SARSCoV-2 infection in patients with systemic vasculitis. Method(s): Observational, multicenter, cross-sectional analytical study in patients 18 or older diagnosed with systemic vasculitis with confirmed SARSCoV-2 infection (RT-PCR or serology) included in the SAR-COVID registry. Patients were evaluated from July 2020 to February 2022. Patients diagnosed with ANCA-associated vasculitis (AAV), other systemic vasculitides (Giant cell arteritis, Takayasu), and a control group of patients with other rheumatological diseases matched by age, sex, comorbidities, and date of SARS-CoV-2 infection. The survival curve of the groups was studied by Kaplan-Meier and compared through the Log-Rank Test. A Cox regression model will be performed to adjust survival for different variables (sex, age, treatments for underlying disease, treatments for viral infection, smoking, obesity, d-dimer level, and disease activity). Result(s): A total of 282 out of 2694 patients in the SAR-COVID registry were included, 57.4%women with a mean age of 55.7 years (SD 14.1). Fifty-four patients in the AAV group, 32 in the other vasculitis group, and 196 controls were studied. Hospitalization was required in 53.7% of the AAV group, 37.5% in other vasculitides, and 26.2% in the control group. 5.6% of patients in the control group presented acute respiratory distress syndrome (ARDS), 15.6% in the other vasculitis group, and 22.2% in the AAV group (p alpha 0.001). Complete recovery was observed in 82.3% of patients in the control group, 75%in the other vasculitis group, and 63%in the AAV group.We observed that 5.7% of the patients in the control group died from COVID-19, 9.4%from other vasculitides, and 27.8% in the AAV group (p alpha 0.001). We found a lower survival in the AAV group compared to the control group (p alpha 0.005). In the multivariate Cox regression model, older age (HR:1.05 IC95%1.01-1.09 p = 0.01), BMI > 40 (HR:13.2 IC95% 2.1-83.2 p = 0.01), and high activity of the underlying disease (HR:16 95% CI 3.7-69.4 p alpha 0.005) were associated with lower survival. Conclusion(s): In conclusion, patients diagnosed with AAV presented a worse disease course during SARS-CoV-2 infection with a more frequent requirement for invasive mechanical ventilation. Likewise, these patients showed lower survival compared to patients with other autoimmune diseases.

Data-Driven COVID-19 Vaccine Development for Janssen

The COVID-19 pandemic has spurred extensive vaccine research worldwide. One crucial part of vaccine development is the phase III clinical trial that assesses the vaccine for safety and efficacy in the prevention of COVID-19. In this work, we enumerate the first successful implementation of using machine learning models to accelerate phase III vaccine trials, working with the single-dose Johnson & Johnson vaccine to predictively select trial sites with naturally high incidence rates ("hotspots"). We develop DELPHI, a novel, accurate, policy-driven machine learning model that serves as the basis of our predictions. During the second half of 2020, the DELPHI-driven site selection identified hotspots with more than 90% accuracy, shortened trial duration by six to eight weeks (approximately 33%), and reduced enrollment by 15,000 (approximately 25%). In turn, this accelerated time to market enabled Janssen's vaccine to receive its emergency use authorization and realize its public health impact earlier than expected. Several geographies identified by DELPHI have since been the first areas to report variants of concern (e.g., Omicron in South Africa), and thus DELPHI's choice of these areas also produced early data on how the vaccine responds to new threats. Johnson & Johnson has also implemented a similar approach across its business including supporting trial site selection for other vaccine programs, modeling surgical procedure demand for its Medical Device unit, and providing guidance on return-to-work programs for its 130,000 employees. Continued application of this methodology can help shorten clinical development and change the economics of drug development by reducing the level of risk and cost associated with investing in novel therapies. This will allow Johnson & Johnson and others to enable more effective delivery of medicines to patients.

Worldwide Trends in Registering Real-World Studies at ClinicalTrials.gov: A Cross-Sectional Analysis.

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice. Methods: A retrospective analysis of 944 studies was performed on February 28, 2023. Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions. Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.

Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

Safety, immunogenecity and effectiveness of ChAdOx1 nCoV-19 vaccine during the second wave of pandemic in India: a real-world study.

OBJECTIVES: This real-world study was conducted to assess the adverse effects following immunization (AEFI) and immunogenicity of ChAdO×1 nCoV-19 vaccine in terms of neutralising antibody titers and to study the effects of covariates such as age, sex, comorbidities and prior COVID status on these outcomes. Also, the effectiveness of the vaccine based on interval between the two doses was also investigated. METHODS: A total of 512 participants (M/F=274/238) aged 35(18-87) years comprising a mixed population of healthcare workers, other frontline workers and general public were enrolled between March and May 2021. Records for adverse events if any were collected telephonically by following up with participants up to 6 months post first dose and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5. Blood samples for measuring antibody titers against the receptor binding domain (RBD) were collected serially using a convenient sampling strategy up to 6 months after the first dose. Data on breakthrough COVID infection was collected telephonically till December 2021. RESULTS: Incidence of local reactions was higher after first dose at 33.4 % (171/512) compared to those after second dose at 12.9 % (66/512). Commonest side effect observed was injection site pain after the first (87.1 %; 149/171) and second (87.9 %; 56/66) dose respectively. Among systemic reactions, fever was the most common manifestation followed by myalgia and headache. Female sex (p<0⸱001) and age less than 60 years (p<0⸱001) had significantly higher predilection for systemic toxicities. Age ≤60 years (p=0.024) and prior-COVID (p<0.001) were found to be significantly associated with higher antibody titers, however, no association was found between these variables and breakthrough COVID infection. Longer spacing between the doses (≥6 weeks) was found to offer better protection against breakthrough infection compared to a spacing of 4 weeks. All breakthroughs were mild-moderate in severity, not requiring hospitalization. CONCLUSIONS: The ChAdOx1 nCov-19 vaccine is apparently safe and effective against SARS-CoV-2 virus infection. Prior COVID infection and younger age group achieve higher antibody titers, but no additional protection. Delaying the second dose up to at least 6 weeks is more effective compared to shorter spacing between doses.

A review of big data and medical research.

Universally, the volume of data has increased, with the collection rate doubling every 40 months, since the 1980s. "Big data" is a term that was introduced in the 1990s to include data sets too large to be used with common software. Medicine is a major field predicted to increase the use of big data in 2025. Big data in medicine may be used by commercial, academic, government, and public sectors. It includes biologic, biometric, and electronic health data. Examples of biologic data include biobanks; biometric data may have individual wellness data from devices; electronic health data include the medical record; and other data demographics and images. Big data has also contributed to the changes in the research methodology. Changes in the clinical research paradigm has been fueled by large-scale biological data harvesting (biobanks), which is developed, analyzed, and managed by cheaper computing technology (big data), supported by greater flexibility in study design (real-world data) and the relationships between industry, government regulators, and academics. Cultural changes along with easy access to information via the Internet facilitate ease of participation by more people. Current needs demand quick answers which may be supplied by big data, biobanks, and changes in flexibility in study design. Big data can reveal health patterns, and promises to provide solutions that have previously been out of society's grasp; however, the murkiness of international laws, questions of data ownership, public ignorance, and privacy and security concerns are slowing down the progress that could otherwise be achieved by the use of big data. The goal of this descriptive review is to create awareness of the ramifications for big data and to encourage readers that this trend is positive and will likely lead to better clinical solutions, but, caution must be exercised to reduce harm.

Impact of pre-existing type 2 diabetes with and without cardiovascular disease on patients with COVID-19.

AIM: To compare adverse outcomes among COVID-19 patients with pre-existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither. METHODS: This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID-19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID-19 infection. Propensity score matching and multivariable analyses were performed. RESULTS: A total of 321 232 COVID-19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow-up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID-19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID-19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed. CONCLUSION: Our study highlights the incrementally poorer outcomes associated with pre-existing T2D + CVD in COVID-19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.