COVID-19 virus: the immune reaction to vaccines

The immune system is developed to preserve its hosts from an ever-expanding cluster of pathogenic microbes. The elimination of toxic substances, allergens, or any other harmful existences that come in, passing the mucosal surfaces, is as well the responsibility of this special system. Its ability to distinguish self (our bodies' functioning cells and tissues) from non-self is the key aspect to its ability to mobilize some reaction to an invasion initiated by the stranger substances listed above. To identify and kill unsafe microorganisms, the host applies both natural and versatile systems, our innate and adaptive immune systems. Vaccines are used to combat the current SARS-CoV-2 strain by utilizing immune system mechanisms, specifically the adaptive immune system. Vectored vaccines, protein vaccines, genetic vaccine, and monoclonal antibody for passive vaccination are among the vaccine platforms under consideration for SARS-CoV-2. Each vaccine has its own benefits and drawbacks. This paper is written to describe the three major forms of COVID-19 vaccines, as well as the unique mechanisms of elements of the immune system associated with the virus. © 2023 SPIE.

BIOLOGIC TREATMENT SUSPENSION AND ASSOCIATED FACTORS IN PATIENTS WITH RHEUMATIC DISEASES DURING THE COVID-19 PANDEMIC: DATA FROM MEXICAN ADVERSE REGISTRY (BIOBADAMEX)

BackgroundThe COVID-19 pandemic triggered serious challenges in the treatment of chronic diseases due to the lack of access to medical attention. Patients with rheumatic diseases (RD) must have adequate treatment compliance in order to reach and maintain remission or low activity of their diseases. Treatment suspension because of non-medical reasons might lead to disease activation and organ damage.ObjectivesIdentify the frequency of biologic treatment (bDMARD) suspension in patients with RD during the COVID-19 pandemic and determine the associated factors for suspension.MethodsIn this study we included all patients registered in the Mexican Biologics Adverse Events Registry (BIOBADAMEX), that started bDMARD before March 2019 and suspended treatment during the COVID-19 pandemic. We used descriptive statistic to analyze baseline characteristics and main treatment suspension causes. We used Chi[2] and Kruskal Wallis tests to analyze differences between groups.ResultsA total of 832 patients patients registered in BIOBADAMEX were included in this study, 143 (17%) suspended bDMARD during the COVID-19 pandemic. The main causes of suspension were inefficacy in 54 (38%) patients, followed by other motives in 49 (34%) patients from which 7 (5%) was loss of medical coverage. Adverse events and loss of patients to follow up were the motive in 16 (11%) and 15 (11%) patients respectively.When we compared the group that suspended bDMARD with the non-suspenders (Table 1), we found statistical differences in patient gender, with 125 (87%) female patients that suspended bDMARD, with a median age of 52 (42-60) years, and a treatment duration of 3.8 years.ConclusionIn our study we found that 17% of patients with RD suspended bDMARD treatment during the COVID-19 pandemic and that non-medical motives such as lack of patients follow up and loss of medical coverage due to unemployment were important motives. These results are related to the effect of the pandemic on other chronic diseases.Table 1.Patients baseline characteristicsPatients that did not suspended bDMARD during pandemic (n = 689)Patients that suspended bDMARD during pandemic (n = 143)pFemale gender, n(%)549 (79.7)125 (87.4)0.02Age, median (IQR)55 (45 – 63)52 (42 – 60)0.04Body mass index, median (IQR)26.4 (23 – 30.4)27.23 (24.2 – 30.46)0.13Social security, n(%)589 (85.5)128 (89.5)0.2Diagnosis0.7- Rheumatoid arthritis444 (64.4)97 (67.8)- Juvenil idiopathic athritis29 (4.2)2 (1.4)- Ankyosing sponylitis93 (13.5)19 (13.3)- Psoriasic arthritis43 (6.2)6 (4.2)- Systemic lupus erithematosus32 (4.6)9 (6.3)- Others48 (6.9)10 (6.9)Disease duration, median (IQR)11 (7 – 19.5)12 (6 - 18)0.95Comorbidities, n(%)305 (44.3)73 (51)0.08Previos biologic, n(%)249 (36.1)60 (42)0.1Treatment at pandemic iniciation, n(%)0.8 - Etanercept a34 (4.9)5 (3.5)- Infliximab a24 (3.5)5 (3.5)- Adalimumab130 (18.9)22 (15.4)- Rituximab a61 (8.9)25 (17.5)- Abatacept76 (11)20 (14)- Tocilizumab82 (11.9)18 (12.6)- Certolizumab92 (13.4)28 (19.6)- Rituximab b7 (1)0- Golimumab36 (5.2)5 (3.5)- Tofacitinib14 (2)1 (0.7)- Infliximab b4 (0.5)2 (1.4)- Etanercept b31 (4.5)6 (4.2)- Baricitinib12 (1.7)1 (0.7)- Belimumab5 (0.7)1 (0.7)- Secukinumb8 (1.2)3 (2.1)Steroids use, n(%):254 (36.9)57 (39.9)0.2Steroids dose (mg), median (IQR)6 (5 – 10)6 (5 – 10)0.47DMARD use, n(%):538 (78.1)118 (82.5)0.1Treatment duration, median (IQR)5.06 (4.04 – 5.78)3.82 (3.35 – 4.95)0.001Suspension motive, n(%)NA- Inefficacy-54 (37.8)- Adverse event-16 (11.2)- Pregnancy-2 (1.4)- Loss of patient-15 (10.5)- Remission-7 (4.9)- Others-49 (34.2)Adverse events, n(%):102 (14.8)24 (16.8)0.3- Severe, n(%)13 (1.9)5 (3.5)0.4a original, b biosimilarREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsVijaya Rivera Teran: None declared, Daniel Xavier Xibille Friedmann: None declared, David Vega-Morales: None declared, Sandra Sicsik: None declared, Angel Castillo Ortiz: None declared, Fedra Irazoque-Palazuelos: None declared, Dafhne Miranda: None declared, Iris Jazmin Colunga-Pedraza: None declared, Julio Cesar Casasola: None declared, Omar Elo Muñoz-Monroy: None declared, Sandra Carrilo: None declared, Angélica Peña: None declared, Sergio Duran Barragan: None declared, Luis Francisco Valdés Corona: None declared, Estefanía Torres Valdéz: None declared, Azucena Ramos: None declared, Aleni Paz: None declared, ERICK ADRIAN ZAMORA-TEHOZOL: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific Advisor in GSK México.

Identifying Promise

Whilst vaccination is progressing at increasing speed, the virus will not disappear, and patients will need safe and effective treatments to reduce the burden of COVID-19," said Stella Kyriakides, commissioner for Health and Food Safety in a press release (3). Promising candidates The five candidates identified by the EC will be prioritized for review, and it is hoped that three of the therapies will gain authorization by October 2021, permitting the final data demonstrate safety, efficacy, and quality. EC, "Register of Commission Expert Groups and Other Similar Entities: High-Level Group on the Health Emergency Preparedness and Response Authority (HERA) and HERA Incubator (E03770)," ec.europa.eu [Accessed 5 July 2021].

Maternal and Neonatal Outcomes After Monoclonal Antibody Use

INTRODUCTION: The study aimed to evaluate whether the administration of monoclonal antibodies (MABs) in mildly symptomatic unvaccinated COVID-19-positive pregnant patients reduced the need for maternal hospitalization and to evaluate whether this medication affected the rate of adverse neonatal outcomes and severe maternal disease. We hypothesized that MAB use would reduce the need for hospitalization. METHODS: This retrospective cohort study was completed by obtaining electronic medical record data of all pregnant patients between August 2020 and January 2022 who met criteria for MAB therapy. The two comparison groups were patients who received outpatient MAB therapy during pregnancy and those who were eligible for therapy but declined. Demographic and hospitalization data were obtained. Exclusion criteria included severe illness upon diagnosis requiring hospitalization, or patients for whom delivery and neonatal data were not available. RESULTS: During the study period, 49 patients qualified for MAB therapy, of which delivery data were available for 39 patients. Twenty patients (51%) elected to receive MAB therapy and 19 (49%) declined. Among those who received MAB therapy, 10 (26% of the population) were vaccinated, and among those who declined, 6 (15% of the population) were vaccinated. The two groups were similar in gestational age at delivery (38 weeks 4 days versus 37 weeks 5 days) and gestational age at diagnosis (19 weeks 0 days versus 22 weeks 6 days). Among patients who did not receive MABs, both absolute and relative maternal hospitalization rate was higher (26.3% versus 5%, 12.8% versus 3%, P >.05). When stratified by vaccination status, those who were vaccinated had a 5% probability of hospitalization regardless of MAB therapy. The probability of hospitalization was highest among unvaccinated women who did not receive MAB therapy (67%) and lowest among unvaccinated women who received MAB therapy (0%). CONCLUSION: Unvaccinated patients who declined MAB therapy had a higher rate of hospitalization, although not statistically significant. These preliminary findings warrant further study with a larger cohort. [ FROM AUTHOR] Copyright of Obstetrics & Gynecology is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

FACTORS ASSOCIATED WITH ADHERENCE TO ANTI TNF-Α THERAPY DURING THE COVID-19 PANDEMIC IN PATIENTS WITH RHEUMATOID ARTHRITIS

BackgroundRheumatoid Arthritis (RA) patients are effectively treated with anti-TNF-α therapy. However, pharmacological non-adherence limits the achievement of the therapeutic objective. This is a multifactorial behavior where factors such as the route of administration, frequency, tolerance, perception of improvement, polypharmacy and social factors are involved [1,2].ObjectivesTo explore the factors associated with non-adherence to anti TNF-α in RA patients during the COVID-19 pandemic.MethodsThis is a cohort of RA patients treated with anti TNF-α in Medicarte SAS, a Colombian center for Immune-Mediated Diseases, between January to December 2021. The program implements strategies such as pharmacotherapeutic support, informed dispensing, phone calls, text messages and home care services to increase adherence. Adherence was defined as dispensing at least 10/12 (>0.80) prescribed monthly doses for 1 year. Sociodemographic characteristics, time in the program, DAS28-CRP, HAQ and treatment were included as exposure variables. For continuous variables, median and interquartile range (IQR) were calculated. Adjusted Odds Ratio (AOR) with logistic regression were calculated, and a p-value <0.05 was considered as statistically significant.Results565 patients were included, 85.8% (n=485) were women, median age 56 years (IQR: 49-65), disease evolution time 13.7 years (IQR: 7.7-20.8), 51% (n=288) had been in the program for more than 3 years, the median time in treatment with anti TNF-α was 3 years (IQR: 1-3) and DAS-28-CRP 2.4 (IQR: 1.6-3.4). The most frequently anti TNF-α prescribed was etanercept 46.0% (n=260), followed by adalimumab 23% (n=130), subcutaneous golimumab 13.3% (n=75), certolizumab 11.0% (n=62) and intravenous golimumab 6.7% (n=38). At the admission, 18.2% (n=103) of the patients had high activity, 38.6% (n=218) mild activity, 9.2% (n=52) low activity and 34% (n=192) were in remission. At the end of follow-up, 6.4% (n=36) of patients had high activity, 18.2% (n=103) mild activity, 14.3% (n= 81) low activity and 61.1% (n= 345) were in remission. The 51.5% (n=291) did not have pharmacological adherence. The use of etanercept (AOR 0.36 CI95% 0.23- 0.58, p < 0.001) and adequate functionality measured through HAQ (AOR 0.64 CI95% 0.42- 0.97, p < 0.04) were associated with a lower risk of non-adherence. Higher DAS28-CRP at the end of follow up was associated with non-adherence (AOR 1.29 CI95% 1.12 - 1.48, p < 0.001).ConclusionDuring COVID-19 pandemic, the implementation of strategies in the home care patient program guaranteed adherence close to 50% in our cohort. Higher values of DAS28-CRP were associated with non-adherence, whilst etanercept use and a normal HAQ value were associated with a higher probability of adherence.References[1]Marengo MF, Suarez-Almazor ME. Improving treatment adherence in patients with rheumatoid arthritis: what are the options? Int J Clin Rheumtol. 2015 Oct 1;10(5):345-356.[2]Smolen JS, Gladman D, McNeil HP, Mease PJ, Sieper J, Hojnik M, et al. Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis: a large cross-sectional study. RMD Open. 2019 Jan 11;5(1):e000585.Acknowledgements:NIL.Disclosure of InterestsWilmer Gerardo Rojas Zuleta Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Mario Barbosa: None declared, Oscar Jair Felipe Díaz Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Adelis Enrique Pantoja Marquez: None declared, Jeixa Canizales: None declared, Carolina Becerra-Arias: None declared, Jorge Hernando Donado Gómez: None declared, Natalia Duque Zapata: None declared.

A serum interleukin-6-based analysis of patients with nasopharyngeal swab reverse-transcriptase polymerase chain reaction negative for SARS-CoV-2 infection with CO-RADS 4 and 5 on computed tomography of the chest

Background: Serum interleukin 6 (IL-6) levels have been studied in the diagnostic evaluation of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19). Methods: We studied the utility of treatment with tocilizumab in COVID-19 patients (n=19) with a negative nasopharyngeal swab real time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 who had suggestive computed tomography (CT) findings, namely, COVID-19 Reporting and Data System (CO-RADS) 4,5. Results: Receiver operator characteristic (ROC) curve analysis showed that serum IL 6 at a cut-off of >56.9 pg/L was a predictor of mortality in nasopharyngeal swab RT-PCR negative patients with suggestive CT findings. Tocilizumab had no significant effect on the mortality. Conclusions: In nasopharyngeal swab RT-PCR negative patients with suggestive chest CT findings, elevated serum IL-6 levels > 56.9 pg/L predicted mortality. However, treatment with tocilizumab had no effect on mortality.

IMPACT OF THE COVID-19 PANDEMIC ON ADHERENCE TO DISEASE MODIFYING DRUGS AMONG PATIENTS WITH RHEUMATIC DISEASES: A POPULATION-BASED, INTERRUPTED TIME SERIES ANALYSIS

BackgroundAlthough studies have quantified adherence to medications among patients with rheumatic diseases (RD) during the COVID-19, lack of direct pre-pandemic comparison precludes understanding of impact of the pandemic.ObjectivesOur objective was to evaluate the effect of the COVID-19 pandemic on adherence to disease modifying drugs (DMARDs) including conventional synthetic (csDMARDs) and targeted synthetic (tsDMARDs).MethodsWe linked population-based health data on all physician visits, hospital admissions, and all dispensed medications, regardless of payer in British Columbia from 01/01/1996 to 3/31/2021. We identified prescriptions for csDMARDs (including methotrexate, hydroxychloroquine) and tsDMARDs, namely anti-TNFs (including infliximab, etanercept, adalimumab) and rituximab using drug identification numbers among indicated individuals with RD. We defined March 11, 2020, as the ‘index date' which corresponded to the date that mitigation measures for the COVID-19 pandemic were first introduced. We assessed adherence as proportion days covered (PDC), calculated monthly in the 12 months before and 12 months after the index date. We used interrupted time-series models, namely segmented regression to estimate changes and trends in adherence before and after the index date.ResultsOur analysis showed that the mean PDCs for all included DMARDs stayed relatively steady in the 12 months before and after mitigation measures were introduced (see Table 1). Adherence was highest among anti-TNFs, methotrexate, and azathioprine. Anti-TNFs were on a downward trajectory 12 months prior to the index date. Interrupted time-series modeling demonstrated statistically significant differences in the trends in PDCs post- vs. pre-mitigation measures for all anti-TNFS (slope [∂]: 1.38, standard error [SE]: 0.23), infliximab (∂: 1.35, SE: 0.23), adalimumab (∂: 0.82, SE: 0.25), and etanercept (∂: 1.07, SE: 0.25) (see Figure 1a). Conversely, the csDMARDs were on a flatter trajectory, and methotrexate (∂: -0.53, SE: 0.16), leflunomide (∂: 0.43, SE: 0.08), mycophenolate (∂: -1.26, SE: 0.48), cyclophosphamide (∂: 0.29, SE: 0.05), minocycline (∂: 0.04, SE: 0.02), chloroquine (∂: 0.02, SE: 0.00) showed statistically significant changes in estimated PDC trajectory after mitigation measures were introduced (see Figure 1b).ConclusionThis population-based study demonstrates that messaging and pandemic mitigation measures did not affect adherence to DMARDs.Table 1.Mean PDC 1 year before and after mitigation measures for the COVID-19 pandemic were introduced.MedicationMean PDC (%) 12 months before index dateMean PDC (%) 12 months after index datecsDMARDsmethotrexate28.926.8azathioprine21.819.5sulfasalazine16.214.9leflunomide14.313.0cyclosporine13.711.5hydroxychloroquine10.59.6mycophenolate4.52.9antimalarials4.43.9penicillamine3.53.4cyclophosphamide1.50.7chlorambucil1.20.4minocycline1.10.9gold0.50.2chloroquine0.10.0tsDMARDsanti-TNFs52.149.2infliximab41.838.3adalimumab40.336.8etanercept31.828.9rituximab3.42.9REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

EFFICACY AND SAFETY OF COVID-19-SPECIFIC TREATMENTS IN SLE: A MULTICENTRE CASE-CONTROL STUDY

BackgroundCOVID-19 is associated with higher morbidity and mortality burdens in immunocompromised individuals, including patients with systemic lupus erythematosus (SLE;1). These patients might benefit from treatment with anti-SARS-CoV-2-specific antiviral agents and monoclonal antibodies, but clinical evidence is to date limited.Objectivesto comparatively assess the course of COVID-19 in patients with SLE treated or untreated with COVID-19-specific agents.MethodsPatients with SLE and COVID-19 treated with antivirals and/or monoclonal antibodies from February 2020 to December 2022 were identified within a three-centre cohort of tertiary referral centres and age-, sex- SLE extension- and SLE duration-matched 1:2 with patients with a history of untreated COVID-19. Data on COVID-19 presentation, course (including time to viral clearance) and sequelae, along with SLE treatment at COVID-19 onset and SLE course after COVID-19 were collected. COVID-19 severity at presentation was quantitated through a 0-4 analogue scale [2]. Data are expressed as median (interquartile range, IQR) unless otherwise specified.ResultsOver three years, 39% of patients with SLE had at least one COVID-19 event. Eighteen subjects (16 women) were treated with antivirals (n=12) or monoclonal antibodies (n=6) and were matched with 36 controls. There was no difference in the frequency of organ involvement between the two groups. Treated patients were receiving significantly higher prednisone daily doses at COVID-19 onset (6.25 (0-10) vs 0 (0-2.5) mg;p=0.005) and had a higher prevalence of previous high-dose steroid treatments (83% vs 47%;p=0.019) compared to controls. SLE disease activity index (3 (0-5) vs 1 (0-4)) and SLE International Collaborating Clinics Damage Index scores (1 (0-3) vs 0 (0-1)) were also numerically higher in treated patients at COVID-19 onset. Patients in the treated group had more severe COVID-19 at presentation but showed no significant differences with control subjects in terms of COVID-19 resolution, prevalence of sequelae and viral clearance (Table 1). There was also no difference in flare occurrence between the two groups (Log-rank=0.02, p=0.889). Two patients reported mild adverse events with monoclonal antibodies (muscle cramps and chest pain, both self-resolving).ConclusionThese data support the safe use of COVID-19 specific treatments in patients with SLE. Patients treated with antivirals and monoclonal antibodies had a favourable COVID-19 course, despite a more severe presentation and a higher risk of deterioration due to SLE and corticosteroid treatment burden, suggesting the potential efficacy of COVID-specific treatments in preventing severe COVID-19 in patients with SLE.References[1]Strangfeld A et al, Ann Rheum Dis, 2021[2]World Health Organization. Clinical management of COVID-19;Interim guidance 27 May 2020.Table 1.COVID-19 presentation and courseTreated (n=18)Untreated (n=36)Number of vaccine doses3 (2-3)3 (2-3)Time from last vaccine administration (days)118 (53-184)134 (30-210)COVID-19 featuresWHO class at presentation1 (1-1)**0 (0-1)Symptoms at presentation: n(%)Dyspnoea3 (17)3 (8)Fever10 (56)22 (61)Upper Respiratory Symptoms16 (89)29 (81)GI symptoms1 (6)2 (6)Pneumonia3 (17)3 (8)COVID-19 courseTime to symptom resolution (days)5 (4-8)7 (3-8)Time to viral clearance (days)10 (7-14)9 (7-14)Any complication: n(%)1 (6)6 (17)Hospitalisations: n(%)1 (6)0 (0)Long COVID: n(%)3 (17)6 (17)Deaths: n(%)0 (0)1 (3)AcknowledgementsWe thank Dr. Giordano Vitali and his staff for assisting and treating patients with SLE and COVID-19 from IRCCS San Raffaele Hospital in the local mild COVID-19 clinic.Disclosure of InterestsGiuseppe Alvise Ramirez Consultant of: Astrazeneca, Maria Gerosa: None declared, Daniel Arroyo-Sánchez: None declared, Chiara Asperti: None declared, Lorenza Maria Argolini: None declared, Gabriele Gallina: None declared, Chiara Bellocchi: None declared, Martina Cornalba: None declared, Isabella Scotti: None declared, Ilaria Suardi: None declared, Lorenzo Beretta: None declared, Luca Moroni Consultant of: strazeneca, Enrica Bozzolo: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB, Lorenzo Dagna Consultant of: Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), and Takeda, Grant/research support from: Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

SAFETY OF BIVALENT SARS-COV-2 VACCINES AS A SECOND BOOSTER DOSE IN ARTHRITIS PATIENTS ON IMMUNOSUPPRESSIVE THERAPIES

BackgroundSafety and efficacy of updated bivalent vaccines, containing both the original vaccine variant of SARS-CoV-2 Spike and either Omicron variants BA.1 or BA.4/5, are of particular interest in arthritis patients on immunosuppressive therapies. With the continuous emergence of new viral variants, it is important to evaluate whether updated vaccines induce more adverse events in this patient group.ObjectivesTo examine if a second booster dose with updated bivalent vaccine increases the risk of adverse events, compared to the first booster dose with monovalent vaccines.MethodsThe prospective Nor-vaC study investigates vaccine responses in patients with immune mediated inflammatory diseases using immunosuppressive therapies (1). The present analyses included arthritis patients who received two booster doses. Patients received available vaccines according to the Norwegian vaccination program. The current recommendation in the Norwegian arthritis population is a three-dose primary vaccination series followed by two booster doses. Adverse events following vaccines doses were self-reported through questionnaires. Adverse events following the first (monovalent) and second (bivalent) booster were compared with McNemar's test.ResultsBetween 7th of July 2021 and 6th of December 2022 a total of 243 arthritis patients (127 rheumatoid arthritis, 65 psoriatic arthritis, 51 spondyloarthritis) on immunosuppressive therapies (Table 1) received a first, monovalent (BNT162b2, mRNA-1273) and a second, bivalent booster dose (BNT162b2 (WT/OMI BA.1), mRNA-1273.214, BNT162b2 (WT/OMI BA.4/BA.5)). Adverse events were recorded within 2 weeks in all patients (Figure 1). In total, 45 vs 49 (19% vs 20 %) patients reported any adverse event after a second, bivalent booster dose, compared to the first, monovalent booster, respectively. There was no significant difference in adverse events overall (p= 0.57). The most common adverse events after the second booster were pain at injection site (12 %), flu-like symptoms (9 %) and headache (6 %). No new safety signals emerged. A total of 15 (6 %) patients reported a disease flare after receiving the second, bivalent booster, compared to 21 (8 %) after the first, monovalent booster.ConclusionThere was no difference in adverse events between the monovalent, first booster, and the bivalent, second booster, indicating that bivalent vaccines are safe in this patient group.Reference[1]Syversen S.W. et al Arthritis Rheumatol 2022Table 1.Demographic characteristics and immunosuppressive medication in patients receiving a 1st monovalent and a 2nd bivalent booster dose.CharacteristicsPatients, n (%)Total243Age (years), median (IQR)61 (52-67)Female152 (63)Immunosuppressive medicationTNFi monoa75 (31)TNFi comboa+b72 (30)Methotrexate62 (26)Rituximab9 (4)IL-inhibitorsc6 (2)JAK-inhibitorsd11 (5)Othere8 (3)1st boosterBNT162b2106 (44)mRNA-1273137 (56)2nd boosterBNT162b2 (WT/OMI BA.1)65 (25)BNT162b2 (WT/OMI BA.4/BA.5)120 (47)mRNA-1273.214 (WT/OMI BA.1)58 (23)Results in n (%) unless otherwise specified.aTumor necrosis factor inhibitors: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol.bCombination therapy: methotrexate, sulfasalazine, leflunomide, azathioprine.cInterleukin inhibitors: tocilizumab, secukinumab.dJanus kinase inhibitors: filgotinib, baricitinib, upadacitinib, tofacitinib.eOther: abatacept, sulfasalazine, leflunomide, azathioprine.Figure 1.Adverse events after bivalent vaccine as a 2nd booster dose compared to a monovalent vaccine as a 1st booster dose.[Figure omitted. See PDF]AcknowledgementsWe thank the patients and health-care workers who have participated in the Norwegian study of vaccine response to COVID-19. We thank the patient representatives in the study group, Kristin Isabella Kirkengen Espe and Roger Thoresen. We thank all study personnel, laboratory personnel, and other staff involved at the clinical departments involved, particularly Synnøve Aure, Margareth Sveinsson, May Britt Solem, Elisabeth Røssum-Haaland, and Kjetil Bergsmark.Disclosure of InterestsHilde Ørbo: None declared, Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Ingrid E. Christensen: None declared, Joseph Sexton: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen-Cilag, Grete B. Kro: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: AbbVie, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: AbbVie, Amgen, BMS MSD, Novartis, Pfizer, UCB, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Siri Mjaaland: None declared, John Torgils Vaage: None declared, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Kristin Kaasen Jørgensen Speakers bureau: Bristol-Myers Squibb, Roche, Sella Aarrestad Provan: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB, Consultant of: AbbVie/Abbott, Galapagos, Pfizer, UCB.

COVID Cholangiopathy Can Occur Despite Mild COVID

Introduction/Objective Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19. Methods/Case Report Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts;repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic. Results (if a Case Study enter NA) NA. Conclusion Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.

CLINICAL CHARACTERISTICS OF PEDIATRIC PATIENTS WITH RHEUMATIC DISEASES UNDER TREATMENT WITH BIOLOGICAL THERAPY: INFORMATION FROM BIOBADAMEX

BackgroundThe advent of biologic treatment (bDMARD) in childhood rheumatic diseases (RD) has changed their evolution and prognosis. Evidence is robust for diseases such as juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE), but in other diseases we still have to learn which is the ideal therapy, time to discontinuation and the potential adverse events (AE) in short and long term.ObjectivesIdentify the clinical and treatment characteristics of pediatric patients with rheumatic diseases with bDMARD treatment and describe the development of AE.MethodsBIOBADAMEX is a prospective ongoing cohort of Mexican patients with RD using bDMARDs since 2016. We included all patients younger than 18 years of age registered in BIOBADAMEX. Descriptive statistics were used for the baseline characteristics and the Chi-square test to analyze the differences between the characteristics of the groups in relation to the development of AE.ResultsA total of 45 patients were included, 31 (69%) of them female, mean age of 13.3 (±3.6) years. (Table 1).The most frequent diagnosis was JIA 25 (56%), followed by SLE 9 (20%), uveitis 5 (11%), polymyositis/dermatomyositis and hidradenitis 2 (4%) respectively;systemic sclerosis and CINCA 1 patient (2%) respectively. The mean duration disease in years was 4.67 (±2.1). Nine patients (20%) used a biologic prior to the current;23 (51%) patients had comorbidities.The most frequent bDMARDs used was Adalimumab (ADA) in 17 (38%) patients followed by Rituximab in 15 (33%) and Tocilizumab in 10 (22%), Infliximab, Abatacept and Canakinumab were used in one patient respectively.When compared by groups, ADA and Tocilizumab were the most used bDMARDs in JIA, Rituximab the only one used in SLE and PM/DM, and ADA the only one for uveitis.15 patients discontinued biological treatment, 4 (27%) due to AE. 82% used an additional synthetic DMARD, being methotrexate the most used in 48% of patients. Steroids were used by 21 (47%) of the patients with a median dose of 10mg (IQR 5 - 25).Fifteen AEs were recorded: 7 (47%) were infections, 5 of these (71%) were COVID;allergies and neutropenia in 2 (13%) patients respectively. By disease infections were more frequent in patients with JIA and Uveitis;neutropenia only occurred in patients with JIA (p 0.95). 87% of the AEs were non-serious, 1 patient with JIA presented a severe AE and one patient with SLE a fatal AE associated with COVID (p 0.93), with no statistically significant difference between groups.ConclusionJIA is the most frequent indication to use bDMARD as worldwide reported. The AE in this analysis are similar to previous registries in terms of the prevalence of infections, in our group the most frequent infectious complication was COVID, being fatal in one patient related with rituximab in SLE. Our study did not find statistically significant differences in the development of AE between diseases;however, they will continue to be reported and the number of patients in the registry will increase.References[1] Sterba,Y.et al. Curr Rheumatol Rep 2016;18,45[2] Fuhlbrigge RC, et al. 2021;47(4):531-543.Table 1.Baseline CharacteristicsBaseline characteristics (n = 45)n%Female, n(%)3168.9Age, media (SD)13.3 (±3.6)Index Body Mass, media (SD)19.6 (±4.9)Dx n(%)n %- JIA25 55.6- SLE9 20- PM/DM2 4.4- Uveitis5 11.1- Hidradenitis2 4.4- Systemic sclerosis1 2.2- CINCA1 2.2Disease duration(years) media (IQR)4.67±2.1Current treatment n(%)n %- Infliximab1 2.2- Adalimumab17 37.8- Rituximab15 33.3- Abatacept1 2.2- Tocilizumab10 22.2- Canakinumab1 2.2Treatment duration (months) median (IQR)4.5 (0.56 – 36.9)Treatment suspension, n(%)15 (33.2)Months to suspension, median (IQR)0.66 (0.46 – 1)Discontinue cause, n(%)n %- Inefficacy1 6.6- Remission1 6.6- Side effects4 26.6- Others5 33.3- Unknown4 26.6Steroids use, n(%):21 46.7Steroids dose (mg), median (IQR)10 5 – 25DMARDs use n(%):37 82.2AE, n(%):15 33.3By disease:AE TypeInfectionAllergyNeutropeniaOtherChi2JIA31230.95SLE1101Uveitis3000Acknowledgements:NIL.Disclosure of InterestsSamara Mendieta: None declare , Alfonso Torres: None declared, Fedra Irazoque-Palazuelos: None declared, Sandra Sicsik: None declared, Iris Jazmin Colunga-Pedraza: None declared, Daniel Xavier Xibille Friedmann: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific advisor in GSK-Mexico, VIJAYA RIVERA TERAN: None declared.

LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt's assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1). The overall UPA safety profile remained unchanged (Figure 1) [1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a (n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/ 48.263.1/54.1*/ 35.787.9/74.4/ 47.861.1/46.6/ 28.786.2/65.2/ 39.8Minimal disease activity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/ 43.458.1/46.7/3 7.678.6/63.5/ 50.954.0/40.8/ 30.379.6/59.9/ 44.6Resolution of enthesitis by Leeds Enthesitis Indexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds Dactylitis Indexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire- Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt's assessment of pain (numeric rating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease Activity Indexf-3.09-3.27-3.16-3.54-2.81-2.71Modified total Sharp/van der Heijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104);data are presented by originally randomized group. bPts with psoriasis affecting ≥3% of body surface area at BL. cPts with LEI >0 at BL;resolution LEI=0. dPts with LDI >0 at BL;resolution LDI=0. eData shown as MMRM (least squares mean) and AO (mean). fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria;ADA, adalimumab;AO, as observed;BL, baseline;MMRM, mixed effect model repeated measurement;NRI, non-responder imputation;PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index;pt, patient;UPA15/30, upadacitinib 15/30 mg once daily;wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB;and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

EXPERIENCE IN THE USE OF NEUTRALIZING MONOCLONAL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19.

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. All rights reserved.

SOME FEATURES OF THE CORONAVIRUS INFECTION COURSE IN BRONCHIAL ASTHMA PATIENTS

The outbreak of a new coronavirus infection was officially recognized by the World Health Organization as a global pandemic since March 11, 2020. The pandemic is currently gradually receding, the number of patients is also steadily decreasing. However, these circumstances are not grounds to believe that the virus has been definitively and irrevocably defeated. For this reason, the world medical community is still concerned about the coronavirus' impact on the course and outcome of various chronic bronchopulmonary diseases. Bronchial asthma has been recognized as one of the leading forms of human somatic pathology throughout the history of mankind and medicine. It is quite natural that the focus of the researchers' attention turned out to be questions about the SARS-CoV-2 virus' impact on patients suffering from bronchial asthma, starting with the peculiarities of the course of combined pathology and ending with the peculiarities of therapy and subsequent rehabilitation. The issues of coronavirus infection and bronchial asthma pathogenesis were considered. The research data on some features of the development and course of a new coronavirus infection in patients with this profile were analyzed and summarized. The low coronavirus infection prevalence among patients with an allergic bronchial asthma form compared with other phenotypes is shown among such features, data on the effect of eosinophilia on the course of infection are presented, and the basic therapy's positive effect using inhaled glucocorticosteroids and/or monoclonal antibodies (biological therapy) in severe asthma, is shown in the form of a protective effect that provides a lighter coronavirus infection course. The main features of patient management suffering from bronchial asthma in the conditions of a pandemic are the organization of stable medical control in online telemedicine once monthly, regular examinations in accordance with the severity of the course of the disease and the correction of basic therapy to achieve complete control over the course of asthma. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

EDQM Combats COVID-19 and Makes Plans for Future

Developers can take them into account to help build appropriate analytical control strategies for their COVID-19 candidate vaccines and ensure the quality and safety of the final product," says Keitel. For USP, building trust in the effectiveness of COVID19 vaccines and treatments, ensuring global access to these treatments, and combating falsified and substandard medicines are the focus, according to Fouad Atouf, PhD, vice president, USP Global Biologics. [...]for existing and new therapies, USP compendial tests and methods address common issues shared by all drug manufacturers, such as suitability, validation, contamination control, stability testing, and qualification of raw materials," Atouf adds. -

Evusheld Prophylaxis Improves Social Interactions, Anxiety, Depression, Agoraphobia, and Quality of Life in Blood Cancer Patients

Evusheld is a combination injection of tixagevimab and cilgavimab and is indicated for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older. Its use has been advocated for immunosuppressed individuals, such as blood cancer patients, although uptake varies significantly between countries. Despite extensive use internationally, there has been limited analysis of potential psychological benefits that vulnerable patients might gain from receiving this prophylactic medication. In this study we have quantified four key psychological health parameters in blood cancer patients who received Evusheld (EQ5D-3L quality of life score, DSM5 Agoraphobia score, Duke's Social Support Index and the hospital anxiety and depression score) and compared their responses with a control group of patients who did not receive Evusheld. We show that patients who opted for treatment had higher baseline markers of psychological stress and ill-health compared with non-treated individuals but that treatment with Evusheld significantly improved the psychological health of recipients and increased the level of physical social/work interactions over that of control patients. Although there are limitations with this small study, the findings strongly suggest that Evusheld prophylaxis can provide significant psychological benefits for vulnerable blood cancer patients who have significant anxiety about COVID-19 infection. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

ADHERENCE TO BIOLOGIC THERAPIES IN INFLAMMATORY RHEUMATIC DISEASES: INFLUENCE OF ROUTE OF ADMINISTRATION

BackgroundInflammatory rheumatic diseases are a debilitating disease affecting the joints and periarticular structures and leading, more or less rapidly, to cartilage and bone destruction. It is a major source of chronic pain and physical, psychological, and social disability, it affect approximately 1% of the world's population [1]. For more than 20 years, biotherapies have revolutionized the treatment of these inflammatory diseases and have largely contributed to the improvement of their prognosis [2]. Adherence to biologic therapies conditions the effectiveness of the treatments then the improvement of patients' quality of life [3].ObjectivesTo evaluate and compare adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) according to the route of administration and the molecule used (Infliximab, Tocilizumab, Etanercept, Adalimumab, Certolizumab, and Golimumab) in patients with inflammatory rheumatic diseases.MethodsThis is a descriptive cross-sectional study with repeated data collection, bi-centric carried out in the rheumatology departments and outpatient clinics at Charles Nicolle Hospital and Rabta Hospital in Tunis and conducted over a period of 01 year and 02 months between 02/02/2021 and 30/04/2022. 71 adult patients with rheumatoid arthritis, spondyloarthritis or juvenile idiopathic arthritis were recruited, their adherence rate in the last 3 months before inclusion should be ≥80%. The collection of socio-demographic, clinical and therapeutic data was established with the help of a pre-established form, from medical files completed by questioning the patients during a direct interview or through a telephone communication. Adherence rate was calculated by determining the ratio of treatments cures (number of biologic injections taken during a year divided by the number of annual biologic injections prescribed).ResultsWithin the study population, adherence was estimated at 85.9%;in the group of patients using intravenous biotherapy was 82.1% (Infliximab 86%, Tocilizumab 75% p=0.04) and in the group of patients using subcutaneous treatment was 89.9% (Golimumab 94%, Etanercept 92%, Certolizumab 89%, Adalimumab 87% p=0.3). Adherence to biologic therapy was significantly higher in the subcutaneous group than in the intravenous group (p=0.01). The causes of poor adherence presented by the patients in this study were: stock-outs of biological treatment and delay in renewal by the national health insurance (CNAM) in thirty-eight cases (54%p<0.001), intercurrent infections in thirty-three cases (46% p=0.005) and the COVID 19 pandemic and its consequences in thirty patients (42%,p=0.28).ConclusionAdherence to biologic treatment is influenced by the route of administration, drugs type, intercurrent infections and drugs availability. All this factors must be treated to improve therapeutic adherence then the efficiency of the biologic therapy which conditions the preservation of physical capacities and an improvement in the quality of life.References[1]Adhésion médicamenteuse et représentations des patients atteints de rhumatisme inflammatoire chronique sous biothérapie: étude ADREP'RI.: 84. Betegnie AL.[2]2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. Singh JA, Saag KG, Bridges SL, Akl EA et al. janv 2016;68(1):1‑26.[3]Adherence to biologic DMARD therapies in rheumatoid arthritis. Expert Opin Biol Ther. Koncz T, Pentek M, Brodszky V, Ersek K, Orlewska E, Gulacsi L. sept 2010;10(9):1367‑78.[4]Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic drugs: a cross-sectional study. Mena-Vazquez N, Manrique-Arija S, Yunquera-Romero L, Ureña-Garnica I, Rojas-Gimenez et al.. Rheumatol Int [Internet]. oct 2017 [cité 30 oct 2022];37(10):1709‑18.[5]Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated Factors in Patients with Rheumatoid Arthritis. Salaffi F, Carotti M, Di Carlo M, Farah S, Gutierrez M. J Clin Rheumatol. déc 2015;21(8):419‑25.Acknowledgements:N L.Disclosure of InterestsNone Declared.

ASYNCHRONOUS TELECONSULTATION BY WHATSAPP CHATBOT IN CONTROLLED AXIAL SPONDYLOARTHRITIS (SPA) PATIENTS UNDER BIOLOGICAL THERAPY: CLINICAL RESULTS OF A SINGLE CENTER

BackgroundThe use of telehealth in the control of rheumatic diseases had been scarce, but COVID pandemic forced to try alternatives to classic face-to-face consultation, and an overflow of telehealth consultations appeared, mainly synchronous (phone, video calls), and finally asynchronous. We try to demonstrate that asynchronous WhatsApp teleconsultation is a good alternative, at least for followup of patients that find it difficult to attend face-to-face visits. We chose axial spondyloarthritis (AxSPA) patients under biological therapy with controlled disease and we proposed teleconsultation with a WhatsApp platform chatbot created for this purpose. The chatbot sends PROMS (BASDAI, VAS for patient global disease assessment, ASDAs, and 3 questions for extraarticular disease), and receive feedback and schedule for the following visits.ObjectivesTo prove that teleconsultation through WhatsApp platform is not inferior to face-to-face consultation in terms of maintaining axial SPA patients disease controlled.MethodsProspective study with retrospective control of patients diagnosed of Axial SPA, fulfilling ASAS criteria and with stable disease under biological therapy for the previous year, recruited from 01 jan to 30 nov 2021. We recruited 62 patients, but two of them gave up (personal reasons, one moved to other region), so we finally include 60 patients. We offer them two teleconsultation visits with their personal mobile device, every four months, and a face-to-face final visit one year after inclusion. In the case of lab test or PROMs deviation or when the patient asks for contact (possible via WhatsApp) he/she is called up by the person in charge (nurse/doctor) that solves the question and arranges an additional presential visit if needed. We consider disease controlled if BASDAI <4, ASDAS < 2,1 or if in rheumatologist´s opinion there is no need to change treatment. We collect patient and disease information (age, gender, employment, characteristics of the disease, previous and actual treatment), activity (BASDAI, PCR, ASDAS), physical function (BASFI), and Quality of life (AsQol).Results60 patients (50 men, 83,3%) were included, mean aged 48,22 years (SD 12,128), 36% were under 45 years at the time of inclusion. They were mostly Ankylosing Spondylitis (AS) (90%;only 6 non radiographic SPA), positive HLA B27 (85%) and with longstanding disease (mean 23 years, SD 12,8), and only 6 patients less than five years. 25% had peripheral impairment (arthritis/dactylitis/enthesitis), and more than 40% presented extraarticular manifestations, mainly psoriasis (26,7%) and uveitis (21%)71,7% were under their first biological (TNF inhibitor, mostly adalimumab), 23,3% were refractory to the first, and 3 patients to at least two biologicals. 51,7% of patients were treated with tapered dose of TNF inhibitors. At inclusion 93,3 % presented remission/LDA by ASDAS/BASDAI-RCP. Only 4 patients included presented higher activity scores but were considered clinically controlled.Table 1.We did not find meaningful clinical differences between basal to final visits in BASDAI, BASFI, ASDAS-RCP or AsQOL.3 patients with reduced dose of biological drug needed to increase to standard dose with no other need to treatment adjustment.ConclusionWe consider asynchronous teleconsultation is promising, and not inferior to face to face consultation in terms of keeping disease control and quality of life, especially for follow-up in patients with stable rheumatic disease, The clinical results presented here are consistent with this considerations.AcknowledgementsGrupo INNOBIDE.Disclosure of InterestsNone Declared.