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BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . 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 Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.
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Disparities in the incidence, prevalence, and morbidity and mortality rates of many respiratory diseases are evident among ethnic groups. Biological, cultural and environmental factors related to ethnicity can all contribute to the differences in respiratory health observed among ethnic minority groups, but the inequalities observed are most commonly due to lower socioeconomic position. People who migrate within a country or across an international border may experience an improvement in respiratory health associated with improvements in socioeconomic position. However, migrants may also experience worse health outcomes in destination countries, as they are faced by barriers in language and culture, discrimination, exclusion and limited access to health services. While some high-quality studies investigating ethnicity and respiratory health are available, further research into ethnic differences is needed. Improving the recording of ethnicity in health records, addressing barriers to accessing respiratory healthcare and improving cultural literacy more generally are some of the ways that inequalities can be tackled.Copyright © ERS 2023.
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BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease, which presents an immune disorder that leads to the production of autoantibodies with potential involvement of multiple organs. Infections are one of the most frequent causes of hospitalization and death in lupus patients, and SARS-CoV-2 infection has been a global threat since March 2020. Immunization of these patients has been strongly recommended, although vaccine evaluation studies have not included this profile of patients.ObjectivesTo evaluate the immunogenicity and safety after 2 doses of the vaccine against SARS-CoV2 in patients with SLE.MethodsSubgroup of SLE patients from the prospective multicenter cohort of patients with immune-mediated diseases "SAFER” – Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease, a phase IV study. Vaccination against SARS-CoV-2 took place with vaccines approved by Brazilian regulatory bodies CoronaVac (Inactivated SARS-CoV-2 Vaccine), ChadOx-1 (AstraZeneca) and BNT162b2 (Pfizer-BioNTech) and this project followed in line with the guidelines of the National Immunization Plan in Brazil. Patients aged 18 years or older with a previous diagnosis of SLE (according to the 2019 ACR/EULAR criteria) were included. Patients were evaluated by telephone contact and in a face-to-face visit on the 28th day after each dose. Patients were followed up by means of blood collection for measurement of IgG antibody against SARS-COV-2 by chemiluminescence and disease activity assessed using SLEDAI-2K score.ResultsA total of 367 individuals with SLE were included, of whom 207 received 2 doses of CoronaVac, 128 received 2 doses of ChadOx-1 and 32 received 2 doses of BNT162b2. 90% of the subjects were female with a mean age of 37 years. About 42% (154) of the individuals included did not have any other associated comorbidity. 50% (182) of patients were using oral glucocorticoids and azathioprine was the most frequent immunosuppressive therapy. Regarding disease activity parameters, 38% (140) of patients had zero SLEDAI-2K at baseline and 41% (147) had zero SLEDAI-2K 28 days after the 2nd dose. Anti-DNA positivity was 30.7% (16/52) at inclusion and 32.6% (17/52) 28 days after the 2nd dose. Complement consumption was present in 18% (10/55) at inclusion and in 14.5% (8/55) 28 days after the 2nd vaccine dose. The geometric mean titers of IgG antibodies against SARS-COV-2 increased in the different vaccine groups, log 2.27 BAU/mL at inclusion and log 5.58 BAU/mL 28 days after the 2nd dose. Antibody titers after second dose varied between different vaccines, 4.96 BAU/mL CoronaVac, 6.00 BAU/mL ChadOx-1 and 7.31 BAU/mL BNT162b2 vaccine, p < 0.001. Only 3.54% (13/367) patients had covid-19 infection after the 15th day of the second dose of immunization, 9 of them having received 2 doses of CoronaVac, 4 of them of ChadOx-1 and none of them receiving BNT162b2, with p-value of 0.63.ConclusionThis study suggests that vaccines against SARS-COV-2 are safe in SLE patients. Induction of immunogenicity occurred in different vaccine regimens. Only 3.5% of individuals had COVID-19 infection with no difference between the types of vaccines evaluated. Future analyzes to explore the association of the effect of immunosuppressive medication, as well as the impact of booster doses and longer follow-up on clinical outcome will be performed.References[1]Mason A, et al. Lupus, vaccinations and COVID-19: What we know now. Lupus. 2021;30(10):1541-1552.[2]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: A multicentre study. Ann Rheum Dis. 2021;80(10):1330-1338.[3]Izmirly PM, Kim MY, Samanovic M, et al. Evaluation of Immune Response and Disease Status in SLE Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. Published online 2021.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.
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BackgroundInfections constitute an important and frequent cause of morbidity and mortality in patients with chronic inflammatory and systemic autoimmune rheumatic diseases. In rheumatoid arthritis (RA), this increased risk has been related to the immune system alterations inherent to the disease, the drugs used to control it (corticosteroids, DMARDs and immunosuppressants) and associated comorbidities. Most studies focus on the search for factors associated with the development of infections but do not explore the worst outcome: patient failure.ObjectivesTo identify factors that help to predict an unfavorable outcome (exitus) after a severe infection in patients with rheumatoid arthritis.MethodsThis study was a retrospective case-control study at a single institution over a 10-year period. Patients with a diagnosis of rheumatoid arthritis with hospital admission for infection from January 1, 2010, to December 31, 2019 (pre-pandemic SARS-COV-2) were selected. The main variable was exitus due to the infectious episode. We collected: age, sex, time of evolution of RA, previous treatment and at the time of admission, number of admissions for infection, location of the infection, comorbidities, and other associated serious diseases. The statistics included a descriptive analysis of the different variables (expressed as median and interquartile range -IR- for quantitative variables and percentages for qualitative variables), and the association study using the χ2 test or Fisher's exact test for qualitative variables, and t-student or Mann-Whitney U and Kruskal Wallis for quantitative variables.ResultsWe obtained 152 patients (71.7% female, 28.3% male), with a total of 214 episodes of admission for infection (115 patients with 1 episode (75.7%), 25 (16.4%) with 2 episodes, 6 being the maximum number of episodes recorded). The median age at admission was 77 years, and the median time of RA evolution was 8 years (IR 4-16). The location of the infection responsible for admission was mainly respiratory and urinary. Forty-eight patients died in the episode (31.6% of the sample, 15 males and 33 females, median age 81.5 years (IR 69.5-86.5)). Comparing the patients with unfavorable outcomes (exitus) with the rest, we only found a statistically significant difference in the number of previous admissions (p=0.011), and in the coexistence of some other serious disease (exitus 85.4%, rest 61.5% p=0.003). There were no differences by sex, age, time of RA evolution, drugs, location of the infection, or comorbidities.ConclusionA history of hospital admission due to infection, and having another serious disease, are factors associated with an unfavorable outcome (exitus) in patients with RA admitted for an infectious process.References[1] Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 2013;52(1):53-61.[2] George MD, Baker JF, Winthrop K, Hsu JY, Wu Q, Chen L, et al. Risk for serious infection with low-dose glucocorticoids in patients with Rheumatoid Arthritis: A cohort study. Ann Intern Med. 2020;173(11):870-8.[3] Singh JA, Cameron C, Noorbaloochi S, Cullis T, Tucker M, Christensen R, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: A systematic review and meta-analysis. The Lancet. 2015;386(9990):258-65.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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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.
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BackgroundA 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed.ObjectivesIt remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.Methods50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.ResultsAt week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781 – 10208] versus 9650 BAU/ml [6633 - 16050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological diseases modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.ConclusionDue to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsDaniel Mrak Consultant of: AstraZeneca, Felix Kartnig: None declared, Daniela Sieghart: None declared, Elisabeth Simader Speakers bureau: Lilly, Helga Radner Speakers bureau: Gilead, Merck Sharp and Pfizer, Peter Mandl: None declared, Lisa Göschl: None declared, Philipp Hofer: None declared, Thomas Deimel: None declared, Irina Gessl: None declared, Renate Kain Speakers bureau: Otsuka, Consultant of: AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag, Stefan Winkler: None declared, Josef S. Smolen Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly, Novartis, and Roche, Thomas Perkmann: None declared, Helmuth Haslacher Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Consultant of: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Grant/research support from: Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Leonhard Heinz: None declared, Michael Bonelli Consultant of: EliLilly.
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Summary Objectives: To describe the characteristics of the population diagnosed with type 2 Diabetes Mellitus (dm2) infected by sars-CoV-2, and to evaluate whether there is an association between dm2 history and covid-19 severity. Method(s): non-probabilistic by convenience sampling, information was obtained from the Online Notification System for Epidemiological Surveillance (sinolave) of the Family Medicine Unit No. 28 of the Mexican Institute of Social Security. A total of 1688 confirmed cases of covid-19 were identified and grouped into patients with and without dm2. Bivariate statistical analysis was performed with Excel 2019 and Stata v. 15.1 programs;measures of association were used using Poisson logistic regression and chi2 test with statistical significance <0.05. Result(s): it was observed that, in patients with covid-19 and dm2, the prevalence ratio of severe acute respiratory infection, diagnosis of pneumonia, hospitalization, and death were higher compared to the group without dm2. Conclusion(s): the frequency, of unfavorable characteristics, was higher in the group of patients with dm2. Health conditions caused by covid-19 reinforce the relevance of an intentional search for undiagnosed diabetic patients, untreated or under treatment with poor glycemic control, in order to avoid major health complications.Copyright © 2023, Universidad Nacional Autonoma de Mexico. All rights reserved.
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BackgroundPatients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome.ObjectivesTo evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group.MethodsDuring the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren's syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated.ResultsCovid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants.ConclusionIn this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable.ReferencesNone.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Objective: To determine the frequency of antibiotic use and to know which clinical and socio-demographic variables were related to the probability of suffering infections associated with COVID-19. Method(s): Adults hospitalized for COVID-19 who received one or more antibiotics during hospitalization were evaluated. We performed a descriptive analysis of variables in the general population' bivariate analysis in two groups (documented vs. suspected infection) and multivariate logistic regression of factors associated with mortality. Result(s): It was determined that 60.4% of adults hospitalized for COVID-19 received antibiotics. Coinfection was documented in 6.2% and superinfection in 23.3%. Gram-negative germs were reported in 75.8% of cultures, fungi in 17.8% and gram-positive in 14.2%. Variables such as age, comorbidities, ICU, anemia, steroids, mechanical ventilation, hemofiltration were statistically significantly related to documented infection. High-flow cannula was associated as a protective factor. Overall mortality was 43.9%, 57.8% in the first group and 38.1% in the second (p=0.002). Conclusion(s): There is a considerable frequency of antibiotic use in subjects hospitalized for COVID-19, particularly related to relevant findings of bacterial superinfection, in those with comorbidities, such as diabetes mellitus, immunosuppression, anemia and fragility, in whom the behavior of the disease is more severe and lethal.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.
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Immunosuppressive drugs are used for treating coronavirus disease 2019COVID-19pneumonia. This study examined the current status of screening and monitoring patients with COVID-19 pneumonia treated with immunosuppressive agents for hepatitis B virusHBVreactivation. Of 123 patients whose hepatitis B surface antigen level was measured, 2 were HBsAg-positive. Antihepatitis B core/surface antibodies were measured in all 121 HBsAg-negative patients. HBV DNA was measured in 31 of 32 patients who were positive for either or both antihepatitis B core/surface antibodies. Of 34 patients requiring regular monitoring, only 4 were monitored. The HBV monitoring rate at the initiation of COVID-19 treatment was high. How-ever, HBV monitoring after COVID-19 treatment was difficult because most patients were transferred to other hospitals or had their treatment terminated.Copyright © 2022 Takeshi Matsui et al.
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The patient presented with fever and appetite loss. Computed tomography (CT) revealed a moderate grade 2 pneumonia. Besides, further blood examination showed his HB antigen as negative, anti-HBs/c anti-body as positive, and HBV DNA level as 1.0 LIU/mL. Therefore, he was diagnosed with COVID-19. Administered treatments comprised oxygen inhalation and steroid therapy, including pulses, remdesivir, and baricitinib, which improved pneumonia. Interestingly, one month posttreatment, his HBV DNA level in-creased to 1.4 LIU/mL, followed by a further increase to 1.7 LIU/Ml, showing an improvement. Tenofovir alafenamide fumarate was thus administered. In clinical practice, immunosuppressive therapy is used for patients with moderate-to-severe COVID-19 pneumo-nia. However, close attention should also be paid to the elevation of blood HBV DNA levels during and after treatment.Copyright © 2022 The Japan Society of Hepatology.
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Organ transplant recipients receive immunosuppressive drugs and hence are at high risk for COVID-19 due to their compromised immunity. This study assessed 1,370 liver transplant recipients who were followed at our hospital. A total of 12 patients got COVID-19: 5 recipients <50-years-old had mild disease, 7 recipients >60-years-old had moderate to severe disease, and 2 patients died. In addition, not all patients received 2 vaccinations, suggesting that the immunization is important for COVID-19 prophylaxis even in this patient population. One recipient was successfully treated with a combination of a reduced dose of immunosuppressive drugs, dexamethasone, remdesivir, and antibiotics, which is being established as an effective therapy for COVID-19.Copyright © 2022 The Japan Society of Hepatology.
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BackgroundThe Covid-19 pandemic has put patients with rheumatic diseases in front of a number of obstacles that had to be solved together with Bulgarian rheumatologists. The lockdowns and restrictive measures have made it difficult for people with rheumatic diseases to have access to timely hospital and pre-hospital care. A number of digital solutions have been implemented to address these issues.ObjectivesTo highlight the problems that patients with rheumatic diseases had during the Covid-19 pandemic;access to rheumatologists and the effectiveness of hospital and pre-hospital care during the pandemic, access to treatment, changes of treatment;communication between physicians and patients, the impact of the pandemic on work, social contacts, hobbies.MethodsAn anonymous survey was conducted online and by telephone. The survey was developed by Medical university, Plovdiv, University hospital "Kaspela”:, Plovdiv, Bulgarian Association for Musculoskeletal Ultrasound, Bulgarian organization for people with rheumatic diseases;Association for patients with autoimmune diseases.Number of participants: 1205 patients with RMD's.Age range: 18-82ResultsFace to face meetings with doctors have been limited during the pandemic.Visits to the rheumatologist's office are significantly reduced and phone, email, text messaging, online consultations were preferred as communication channels.Before the pandemic, 76% of respondents most often communicated with their physicians by visiting their practice, during the pandemic their relative share decreased to 46%, with a significant difference of 30%Phone consultations: patients using this type of communication increasing from 38% before the pandemic to 56% during the pandemic, a significant difference of 18%The percentage of patients who communicated via text or email rises from 10% to 17 %.It has become apparent that Digital transformation is needed and patients and physicians should work together to achieve it and to be established in Bulgaria.245 patients reported a change in their treatment. Of these: (30%) reduced the dose of their medications, 119 (49%) increased the dose and the remaining 55 (21%) stopped their therapy.From the responses of the respondents, it is clear that 71% have not experienced a change in their work during the COVID-19 pandemic, 17% have worked from home.From the responses of the respondents, it is clear that 71% have not experienced a change in their work during the COVID-19 pandemic, 17% have worked from home, 4% have been fired, 3% have left their jobs due to the risk of their health and 5% left their jobs for other reasons.ConclusionThe Covid-19 pandemic has shown that the digital transformation in rheumatology care can be an efficient alternative to some of the services offered to patients with rheumatic diseases in Bulgaria (especially secondary examinations and therapy monitoring examinations). The results of the conducted survey could be used to support digitization in healthcare in Bulgaria.Very important was the collaboration between the patient organizations and the Bulgarian Association for Musculoskeletal Ultrasound, Medical University, Plovdiv and the rheumatologists from University hospital "Kaspela” Plovdiv.References[1]Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 2020;79: 859–66.[2]Monti S, Balduzzi S, Delvino P, Bellis E, Quadrelli VS, Montecucco C. Clinical course of COVID-19 in a series of patients with chronic arthritis treated with immunosuppressive targeted therapies. Ann Rheum Dis 2020;79: 667–68.[3]Dejaco, C.;Alunno, A.;Bijlsma, J.W.;Boonen, A.;Combe, B.;Finckh, A.;Machado, P.M.;Padjen, I.;Sivera, F.;Stamm, T.A.;et al. Influence of COVID-19 pandemic on decisions for the management of people with inflammatory rheumatic and musculoskeletal diseases: A survey among EULAR countries. Ann. Rheum. Dis. 2020AcknowledgementsBul arian organization for people with rheumatic diseases.Association for patients with autoimmune diseases.Bulgarian Association for Musculoskeletal Ultrasound.Disclosure of InterestsNone Declared.
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BackgroundAmid the coronavirus disease 2019 (COVID-19) crisis, two messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have benefited most people worldwide. While healthy people can acquire sufficient humoral immunity against COVID-19 even in the elderly by vaccination with three doses of vaccine., recent studies have shown that complex factors other than age, including the type of vaccines and immunosuppressive drugs, are associated with immunogenicity in patients with rheumatic musculoskeletal disease (RMD). Identifying factors that contribute to the vulnerability of those patients to acquire not only humoral but also cellular immunity to SARS-CoV-2 despite multiple vaccinations is crucial for establishing an appropriate booster vaccine strategy.ObjectivesTo assess humoral,and T cell immune responses after third doses of mRNA vaccines against SARS-CoV-2.MethodsThis prospective observational study included consecutive RMD patients treated with immunosuppressant who received three doses of mRNA vaccines including BNT162b2 and mRNA-1273. Blood samples were obtained 2-6 weeks after second and third dose of mRNA vaccines. We measured neutralizing antibody titres, which against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 and seroconversion rates to evaluate the humoral responses. We also assessed T-cell immunity responses using interferon releasing assay against SARS-CoV-2.ResultsA total of 586 patients with RMD treated with mmunosuppressive treatments were enrolled. The mean age was 54 years, and 70% of the patients were female. Seroconversion rates and neutralizing antibody titres after third vaccination of SARS-CoV-2 were significantly higher compared to those after second vaccination (seroconversion rate, 94.5% vs 83.6%, p<0.001;titres of neutralizing antibody, 48.2 IU/mL vs 11.0 IU/mL, p<0.001, respectively). Interferon releasing assay after third vaccinations demonstrated that T cell reaction against SARS-CoV-2 was also increased from that of second vaccination (interferon for antigen 1, 1.11.9 vs 0.61.9, p=0.004,interferon for antigen 2, 1.72.6 vs 0.82.3, p=0.004). Humoral and cellular immunogenicity did not differ between the types of third vaccination including full dose of BNT162 and half dose of mRNA1273.(neutralizing antibody titers, 47.8±76.1 IU/mL vs 49.0±60.1 IU/mL, p<0.001;interferon for antigen 1, 1.12.0 vs 1.01.5, p=0.004, respectively). Attenuated humoral response to third vaccination was associated with BNT162b2 as second vaccination age (>60 years old), glucocorticoid (equivalent to prednisolone > 7.5 mg/day), and immunosuppressant use including mycophenolate, and rituximab. On another front, use of mycophenolate and abatacept or tacrolimus but not rituximab were identified as negative factors for T-cell reactions against SARS-CoV-2. Although 53 patients (9.0%) who had been immunised with third-vaccination contracted COVID-19 during Omicron pandemic phase, no one developed severe pulmonary disease that required corticosteroid therapy.ConclusionOur results demonstrated third mRNA vaccination booster of SARS-CoV-2 contributed to restore both humeral and cellular immunity in RMD patients with immunosuppressants. We also identified that certain immunosuppressive therapy with older RMD patients having BNT162b2 as a second vaccination may need additional booster vaccination.Reference[1]Furer V, Eviatar T, Freund T, et al. Ann Rheum Dis. 2022 Nov;81(11):1594-1602. doi: 10.1136/ard-2022-222550.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.