RHEUMATOID ARTHRITIS FLARE FOLLOWING COVID-19 VACCINATION IN MALAYSIAN POPULATION AND ITS ASSOCIATED RISK FACTORS

BackgroundFlare of Rheumatoid Arthritis (RA) following COVID-19 vaccination has been reported with a low occurrence observed in those patients with disease remission. However, no local data is available in our multi-ethnic Malaysian population.ObjectivesTo evaluate the prevalence of RA flare in Malaysian patients following COVID-19 vaccination and its associated risk factors.MethodsThis was a cross-sectional study assessing RA flare based on patient-reported disease flare through self-administered questionnaires and physician-reported flare. Patient self-reported disease flare was defined as ‘a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as ‘an increment of disease activity score 28-joint documented within 3 months post-vaccination‘ from either a scheduled or unscheduled clinic visit. A total of 186 RA patients attended the rheumatology clinic in Hospital Putrajaya from May to July 2022 who completed the primary COVID-19 vaccination under the Malaysian National Vaccination Programme were recruited. Demographic data, disease parameters including serology for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), cessation of disease modifying anti-rheumatic drugs (DMARDs) around vaccination, type of vaccines and adverse events were examined using descriptive and univariate analyses.ResultsMajority (93%) of RA patients enrolled were female with a mean age of 58 years old (standard deviation, SD 12.2) and mean disease duration was 12 years (SD 7.7). More than half were seropositive (66% RF, 63% ACPA) with 47.4% had double seropositivity (RF and ACPA positive). All patients received DMARDs with the majority (71%) were on methotrexate (MTX), 21.5% were on leflunomide, 17.7% on other DMARDs, with a small proportion (14%) of patients were receiving prednisolone. Only 4.8% of patients were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. Half of the patients were in remission prior to vaccination. 62% of patients received Pfizer-BioNTech vaccine as the primary vaccine, followed by Sinovac-CoronaVac (24.6%) and Oxford-AstraZeneca (13.4%) vaccines. A booster dose had been administered to 80% of patients, of which 88.7% was Pfizer-BioNTech vaccine. MTX therapy were discontinued in 39.4% of patients (n=52) post-vaccination for a week duration. The prevalence of RA flare was only 12.9% (n=24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Flare rates were higher during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. Common vaccine adverse effects were fever (16.8%), myalgia (8.6%) and arthralgia (6.4%). There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and prednisolone, and discontinuation of MTX post-vaccination. Although seropositivity did not exhibit statistically significant flare rate post vaccination, sub-analysis revealed four times higher rate of flare in those who has double positivity compared to seronegative RA patients (12% vs 4%).ConclusionPrevelance of RA flare post-COVID-19 vaccination in Malaysian RA population is low. No significant associated risk factors were identified although double seropositivity appeared to have higher number of flares.References[1]Bixio, R., Bertelle, D., Masia, M., Pistillo, F., Carletto, A. and Rossini, M. (2021), Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019 Vaccination in Patients With Rheumatoid Arthritis in Remission. ACR Open Rheumatology, 3: 832-833.[2]Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, Lai FTT, Wan EYF, Wong CKH, Chan EWY, Lau CS, Wong ICK. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022 Apr;81(4):564-568.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

LONG-TERM AND BOOSTER VACCINATION RESPONSES IN PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA

BackgroundVaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) [1].ObjectivesHere, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination.MethodsGCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively).ResultsAntibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies.ConclusionThese results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used >10mg/day prednisolone or methotrexate during primary vaccination.Reference[1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.

EFFECTS OF DMARD TREATMENT ON SARS-CoV-2 mRNA VACCINATION IN PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASE: A MATCHED, PROSPECTIVE COHORT STUDY

BackgroundPatients suffering from systemic autoimmune rheumatic disease (SARD) display poor antibody development after two doses of mRNA vaccinations leaving these patients with only limited humoral protection against severe SARS-CoV-2 disease courses. Of key interest is the effect of conventional synthetic (csDMARD) and biological/ targeted drugs (b/tsDMARDs) disease modifying antirheumatic drugs on the time of protection.ObjectivesTo compare antibody titer development in patients with vasculitis and connective tissue disease (CTD) with healthy controls 6 months after two mRNA vaccinations and after third immunization. To analyze factors, that affect the velocity of titer decline, well as qualitative humoral response.MethodsPatients with SARD were enrolled and matched for gender and age with healthy control subjects (HC) and the humoral response after 6 months to two doses of mRNA vaccine BNT162b2 in terms of SARS-COV-2 antibody titer was assessed. In addition to binding antibody units (BAU) we also analyzed neutralizing antibodies. Patients receiving B-cell depleting therapy and those with prior SARS-CoV-2 infection (via detection of nucleocapsid antibodies) were excluded. Differences between two groups were calculated with Wilcoxon signed-rank test.ResultsA total of 53 patients with SARD (42 patients suffering from connective tissue disease and 11 with vasculitis respectively) and 73 HC were analysed. Interestingly only patients receiving a combination therapy of different csDMARDs/ b/tsDMARDs demonstrated diminished antibody titers 6 months after two doses of mRNA vaccine (p-value p-value<0,001), whereas patients receiving only csDMARD as monotherapy displayed comparable antibody levels to healthy controls. This effect was equalized after a third booster vaccination (p-value=0,13). Concerning disease entities, patients with vasculitis seemed to have lower BAU than HC (p-value<0,05) and patients suffering from CTD. After third vaccination both patient groups had lower antibody levels than HC (vasculitis: p-value <0,0001;CTD: p-value p-value<0,01). Lower antibody levels before third vaccination correlated with lower antibodies after third immunization.ConclusionPatients with autoimmune rheumatic diseases undergoing combination therapy may be more vulnerable to SARS-CoV-2 infection, due to reduced antibody levels 6 months following two doses of mRNA vaccine. Our data strongly recommends antibody measurements in patients receiving combination therapy and individualized earlier booster vaccination.Figure 1.Anti-SARS-Cov-2 S antibody titers. A: Antibody titers measured 6 months after two doses of mRNA vaccination in patients with connective tissue disease, vasculitis and healthy controls. B, Antibody levels according to disease entity. AB: antibody;BAU: binding antibody unit;CTD: connective tissue disease;HC: healthy control;mono: disease modifying anti-rheumatic drug monotherapy;combination: combination therapy of disease modifying anti-rheumatic drugs;RBD: receptor binding domain;[Figure omitted. See PDF]Table 1.Demographic parameters and therapy of study participants.SARD (n=53)HC (n=73)Age, mean (standard deviation)53.55 (±14.04)51.27 (±14.07)Female45 (84.9%)47 (64.4%)Connective tissue disease42 (79%)Vasculitis11 (21%)csDMARD or b/tsDMARD monotherapy22 (41%)csDMARD and/or b/tsDMARD combination therapy13 (25%)No therapy18 (34%)Methotrexate8 (15%)Mycophenolate mofetil10 (19%)Hydroxychloroquine17 (32%)Azathioprine8 (15%)Belimumab3 (6%)Tocilizumab3 (6%)Glucocorticoid dose 1. vaccination, mean (standard deviation)2.8 (±10.8)Glucocorticoid dose 2. vaccination, mean (standard deviation)2.6 (±10.7)SARD: Systemic autoimmune rheumatic disease, HC: Healthy controls, csDMARD: conventional synthetic disease modifying antirheumatic drugs and b/tsDMARD: biological/ targeted drugs disease modifying antirheumatic drugsREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsElisabeth Simader Speakers bureau: Lilly, Thomas Deimel: None declared, Felix Kartnig: None declared, Selma Tobudic: None declared, Helmuth Hasla her Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Thomas Maria Karonitsch: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Lechner-Radner: None declared, Judith Sautner: None declared, Florian Winkler: None declared, Heinz Burgmann Speakers bureau: speaker fees from Shionogi, Pfizer, MSD, Paid instructor for: advisory boards for Valneva, MSD, Gilead, Consultant of: consulting fees from MSD, Pfizer, Takeda, Gilead, Daniel Aletaha Speakers bureau: other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: personal fees from Abbvie, personal fees from Novartis, Peter Mandl Speakers bureau: reports speaker fees from AbbVie, Janssen and Novartis, Grant/research support from: research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB.

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.

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.

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.

EVALUATION OF TELENURSING FOLLOW-UP IN A COHORT OF STABLE/LOW DISEASE ACTIVITY PATIENTS WITH INFLAMMATORY ARTHRITIDES: A FEASIBILITY STUDY

BackgroundPeriodic follow-up (FU) is necessary for patients with Rheumatic Diseases (RDs). In the case of a stable clinical condition or low disease activity, FU can be carried out also by rheumatology nurses (RNs). Recent studies focusing on FUs led by RNs either in Rheumatology Clinics and with Telenursing (TN), showed promising results in terms of outcomes, cost reduction and users' satisfaction.ObjectivesTo evaluate the feasibility of a Telenursing FU in a Rheumatology Centre in Florence, Italy.MethodsIn this pilot study, patients with stable inflammatory arthritis or low disease activity were contacted, after their first visit, through TN (T0) and then assessed during the following in-person visit (V12) by RNs for treatment adherence, for pain, for mental and physical health, for workability, for perception of disease activity and satisfaction concerning the TN service.ResultsOut of 27 interviewed patients, 59.3% (n=16/27) was affected by Rheumatoid Arthritis (RA), 18.5% (n=5/27) by Spondyloarthritis (AS), 14.8% (n=4/27) by Psoriatic Arthritis (PsA) and 7.4% (n=2/27) by Juvenile Idiopathic Arthritis. The mean age was 57.5±13.1 (M± DS) years and the treatment adherence level was optimal. 11.1% (n=3/27) of patients was referred for medical consultation because of the urgent clinical situation assessed by the RNs according to the clinical multidisciplinary checklist. After specialist consultation, 1 patient was revalued in presence for a transient ischemic attack;1 patient was contacted by the rheumatologist following independent discontinuation of methotrexate therapy;1 patient was redirected to urgent dermatology consultation because of a suspected cutaneous drug reaction.During the TN period (12 months), 33.3% (n=9/27) of the patients contracted SARS-CoV-2 infection and 11.1% (n=3/27) contracted urinary or upper respiratory tract infections.RA patients showed a mean Rheumatoid Arthritis Impact of Disease-RAID score of 2.4 at T0 and 2.5 at V12 (Range 0-10);AS patients showed a mean Assessment of Spondyloarthritis International Society-ASAS score of 0.3 in both periods and PsA showed a mean Psoriatic Arthritis Impact of Disease-PSAID score of 0.7 and 0.8 at T0 and V12, respectively. Among RA, AS and PsA patients, as a pain score of 3 was recorded in both periods.In order to attend the in-person FU visit, 68.4% (n=13/19) of the patients took work leave. 37% (n=10/27) of them waited 40.9±18.6 minutes at V12 control. The average distance between the Rheumatology Centre and patients' home was 29.3±25.6 km. 15.4% (n=5/13) of the respondents did not own a car and 23.1% (n=3/13) was accompanied to visit by their caregiver.All the included patients expressed high satisfaction for the TN service, corresponding to 5 point Likert scale.ConclusionThe data show that TN FU is a valuable model for maintaining an adequate level of therapeutic adherence, reducing the travel time and working day loss, intercepting remotely clinical issues, as well as registering a high level of user acceptance and satisfaction. Further studies on larger samples are needed to confirm our findings.References[1] Bech B et al (2020) 2018 update of the EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis. Annals of the Rheumatic Diseases;79:61-68. doi: 10.1136/annrheumdis-2019-215458.[2] Alcazar B, Ambrosio L. (2019) Tele-nursing in patients with chronic illness: a systematic review. An Sist Sanit Navar;42(2):187-197. doi: 10.23938/ASSN.0645.[3] Larsson I et al. (2013) Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. Journal of Advanced Nursing;70(1), 164–175., 2013 doi:10.1111/jan.12183Acknowledgements:NIL.Disclosure of InterestsNone Declared.

EVALUATION OF PATIENT SATISFACTION WITH REMOTE SELF-INJECTION TRAINING: A SINGLE-CENTRE PATIENT-REPORTED SURVEY

BackgroundSubcutaneous self-injection of methotrexate (SC MTX) is used for the treatment of several inflammatory diseases. All newly initiated patients should be educated and trained in the proper injection technique by their healthcare provider (HCP), with the first injection performed under medical supervision. This training has typically been conducted during face-to-face consultations, however since the start of the COVID-19 pandemic it has been necessary to conduct training remotely due to the cancellation of clinics.ObjectivesTo understand patient-reported experiences and satisfaction with remote SC MTX self-injection training.MethodsA cross-sectional electronic survey was administered between 11 October 2022 and 30 November 2022 to patients at Southern Health and Social Care Trust who had recently been trained via telephone or video conference [VC] on how to self-inject methotrexate using a pre-filled, auto-injector pen. Patients were aged ≥18 with a range of arthritis types, including rheumatoid, psoriatic, polyarticular juvenile idiopathic and chronic reactive inflammatory arthritis. Remote training was delivered by the patient's nurse as per routine practice (independently of this survey). Patients were sent a patient information pack (PIP) prior to the training consultation. During the training, the nurse discussed the process of injecting with the auto-injector pen before virtually supervising the first injection.The survey consisted of 14 questions;topics included experiences and satisfaction with preparation for the HCP appointment, the training consultation itself and post-training experiences and preferences. The responses were analysed descriptively on an item-by-item basis.ResultsIn total 73 patients completed the survey;77% (n=56/73) were female, and 96% (n=70/73) had no prior experience with a SC MTX auto-injector pen. The training was completed by telephone for 92% (n=67/73) of patients and by VC for 8% (n=6/73). 99% (n=72/73) received a PIP in advance of their training consultation and 92% (n=67/73) received this by post. 67% (n=49/73) of patients strongly agreed and 26% (n=19/73) agreed that they felt prepared for the training after receiving the PIP;78% (n=57/73) of patients strongly agreed and 22% (n=16/73) agreed that it was easy to read and understand, whilst 52% (n=38/73) strongly agreed and 32% (n=23/73) agreed that the PIP was helpful and did not require additional instructions before the appointment. 84% (n=61/73) took 15 minutes or less to complete the training with their HCP. None of the participants felt confused or did not understand the training instructions from their HCP, 78% (n=57/73) strongly agreed and 19% (n=14/73) agreed that the remote training was helpful and made them feel more confident to use the injector pen on their own and 97% (n=71/73) did not need to contact their HCP for more training or advice following their appointment. When asked about the main advantages of remote training, 32% (n=23/73) agreed it was more convenient, 25% (n=18/73) agreed that it was time saving and 30% (n=22/73) agreed that not having to attend the hospital was beneficial. 85% (n=62/73) strongly agreed and 14% (n=10/73) agreed that they were satisfied with the remote training provided and 82% (n=60/73) strongly agreed and 18% (n=13/73) agreed that they would recommend the remote training to another patient.ConclusionThese findings provide new insight into patients' experiences with self-injection training when delivered remotely by their HCP. The patient information pack and training consultation were well received as most patients found it helpful, convenient and time saving.References:NIL.AcknowledgementsThis survey was funded by Nordic Pharma. Medical writing support was provided by Angie Bonsu of Open Health and funded by Nordic Pharma.Disclosure of InterestsShannon McCourt Grant/research support from: Nordic Pharma, Mano Andiappan Employee of: Open Health who were paid by Nordic Pharma to support the work described in the .

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

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.

WHAT DO USERS OF RHEUMATOID ARTHRITIS ONLINE FORUMS TALK ABOUT? APPLYING A DEEP LEARNING APPROACH TO UNCOVER COMMON THEMES

BackgroundSocial media platforms have become a vital resource for individuals seeking information and support regarding health issues, including rheumatoid arthritis (RA). As such, the content generated on these platforms represents a valuable source of data for gaining insight into patients' perspectives on RA. However, previous research in this area has primarily relied on qualitative analyses of small sample sizes, limiting the ability to extract meaningful insights from social media content related to RA. With the advancement of machine learning techniques, it is now possible to analyze and extract insights from large volumes of social media posts related to RA.ObjectivesThe purpose of this study was to identify the most common topics discussed in a large dataset of submissions about RA on Reddit, one of the world's largest online forums.MethodsThe data for this study was collected from the two largest Reddit forums ("subreddits”) dedicated to RA, r/rheumatoid arthritis and r/rheumatoid, which have 18.9k and 7.6k members respectively. We retrieved all submissions but excluded responses in our analyses. All deleted or duplicate submissions and those with fewer than 10 words were removed, retaining 11,094 submissions from over 5,000 users for the analysis. To identify common themes, we applied topic modeling, a technique in natural language processing that identifies underlying themes or topics in a collection of documents. We used the Bertopic Python package (Grootendorst, 2022), which employs deep learning techniques to perform the topic modeling.ResultsThe data indicates a significant increase in submissions to the two subreddits, rising from 113 in 2014 to 2892 in 2021 and 1928 in the first 8 months of 2022. Upon analysis, 65 topics were identified, with 4162 submissions (37.5%) remaining unclassified. A topic specifically dedicated to requests to participate in surveys was removed as it did not pertain to the experiences of forum users. Among the remaining topics, the top 10 accounted for 44.90% of all submissions. To better understand each topic, a sample of 10 submissions with the highest probability for that topic were examined (Table 1).Table 1.Top 10 most frequent topicsTopicn of submissionsShare of total*Side effects of methotrexate5268.02%COVID & vaccines4627.04%Mental health4386.68%RF and anti CCP test results3315.04%RA of friends, partners, and close relatives2623.99%Complaints about rheumatologist2123.23%Questions about Humira1882.87%Questions about prednisone1822.77%Diets and RA1752.67%Early symptoms of possible RA1702.59%Exercise and RA1682.56%* After excluding unclassified topicsThree of the ten topics pertained to specific medications - methotrexate, Humira, and prednisone, accounting for 12.71% of the total. The most prevalent topic, at 8.02%, focused on the side effects of methotrexate, with many submissions inquiring about symptoms such as nausea. The second most common topic, at 7.04%, primarily revolved around COVID-19 and related issues, with some pre-COVID vaccine discussions also included. In 2021, COVID-related discussions were the most prevalent topic. The third most frequent topic (6.68% of total), dealt with mental health and the emotional struggles faced by those living with RA.ConclusionThe surge in submissions on Reddit demonstrates its growing popularity as an online forum for discussing topics related to RA. Utilizing deep learning-based topic modeling has proven to be an effective method for extracting meaningful topics from the questions and experiences shared by users. The vast amount of data generated by Reddit, in combination with advanced machine learning techniques, enables both an overview of the various topics discussed and a detailed examination of specific topics. This makes the use of social media data a valuable source of insight into the concerns of RA platform users.Reference[1]Grootendorst, M. (2022). BERTopic: Neural topic modeling with a class-based TF-IDF procedure. arXiv preprint arXiv:2203.05794.Acknowledgements:NIL.Disclosure of InterestsNone Decla ed.

COVID-19 AND ADVERSE MENTAL HEALTH OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS

BackgroundThe COVID-19 outbreak is known to increase the fear level of most patients with chronic diseases. Patients with rheumatoid arthritis (RA) are very vulnerable to environmental stress. During this pandemic, the psychological pressure may be further increased due to the perplexing nature of information about the risk of infection in RA patients.ObjectivesThe objective of this study was to determine the impact of the COVID-19 pandemic on the mental health of RA patients and to investigate associated factors.MethodsThis is a cross-sectional study of 190 patients with RA who met the ACR/EULAR 2010 criteria. For each patient, we collected sociodemographic, clinical, and biological data. Depression and anxiety were assessed by the Hospital Anxiety and Depression scale (HADs) and disease activity by the DAS-28 score.ResultsThe average age of our patients was 55 years with a female predominance (86.3%). The average duration of the disease was 8 years. The mean DAS 28 score was 4.1 ±1.03. The disease was deforming in 52.9% of cases. All of us patients were on disease-modifying therapy, 87.1% were on methotrexate and 12.9% were on biotherapy. Sixty patients (31.57%) had contracted SARS-CoV-2.During the pandemic, depression was present in 38.4% of patients. It was mild in 33.1% of cases, moderate in 4.1%, and severe in 1.2% with a mean HADs depression score of 4.4 ± 3.1. This score was significantly higher in patients with a history of SARS-COV-2 infection in a family member (p=0,002), comorbidities (p<0.001), joint deformities (p=0.008), and high disease activity (p<0.001). Anxiety was present in 55.6% of patients. It was mild in 32.6% of cases, moderate in 20.6%, and severe in 2.4% of cases with a mean HADs anxiety of 6.4 ± 3.9. The presence of anxiety was correlated with fear of COVID-19, higher disease activity, the presence of comorbidities, and the presence of deformities (p<0.001 for all cases). This score was also significantly higher in the illiterate (p<0.001) and unemployed patients (p=0.001).ConclusionIn our study, depression and anxiety were frequent in RA patients during the COVID-19 pandemic. These psychological disorders were more common in patients with active and disabling RA associated with comorbidities. As the pandemic continues, more patients are susceptible to experience anxiety and depression. Therefore, rheumatologists must remain vigilant to these psychological alterations and provide the necessary support.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS & OUTCOMES AMONG PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES AND SARS-CoV-2 INFECTION: 2-YEAR DATA FROM A TERTIARY RHEUMATOLOGY CENTRE IN GREECE

BackgroundPatients with autoimmune rheumatic diseases (ARDs) under moderate/severe immunosuppression are considered a high-risk population to develop severe Covid-19 infection.ObjectivesThe aim of our study was to describe the clinical characteristics and the outcome of patients with ARD who contracted a Sars-Cov-2 infection.MethodsAmong patients with ARD being followed in our tertiary outpatient rheumatology clinic, we retrospectively identified those infected with SARS-CoV-2 between the beginning of the pandemic and August 2022. Patients' medical files were reviewed for demographics (age, gender and comorbidities) and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, treatment, and outcomes (covid-19 severity, hospitalization, death).ResultsA total of 209 cases of ARD patients with confirmed Covid-19 infection were recorded. Most of them were women (62.7%), with a mean age of 52.4± 13.8 years. The most prevalent ARDs were seronegative spondyloarthropathies (28.7%), systematic lupus erythematosus (21.5%), rheumatoid arthritis (16.5%), and systemic sclerosis (11.5%). More than half of the patients received corticosteroids (57.8%), while the most frequently used immunosuppressants were hydroxychloroquine (30.9%), TNF inhibitors (26.5%), mycophenolate mofetil (24.0%), methotrexate (19.1%) and rituximab (15.2%). One hundred and fifty-eight (76%) patients were either on remission or had mild disease activity. Most of the patients (131/209) had at least one comorbidity, more commonly arterial hypertension (48.5%) and pulmonary disease (45.2%). Most of the patients were vaccinated against Sars-Cov-2 (73.7%), either with two doses (38.0%), three doses (57.0%) or four doses (5.0%) of mRNA-based vaccines. The big majority of the patients (83.3%) were asymptomatic or had mild Covid-19 disease. About half of the patients (53.1%) reported to have received Covid-19 treatment. Thirty-two of them (15.3%) needed hospitalization, and five death cases were reported overall. Among the demographic characteristics, age (p<0.0001 for hospitalization) and comorbidities were associated with worse covid-19 outcomes. In particular, cardiovascular disease (OR 5.37, p=0.001 for covid-19 severity, OR 6.89, p=0.001 for hospitalization), pulmonary disease (OR 3.02, p=0.006 for hospitalization), and obesity (OR 3.46, p=0.044 for hospitalization) had the stronger associations. Non-vaccination status was also associated with a higher risk for hospitalization (OR 2.68, p=0.015). In relation to ARD-related factors, treatment with rituximab (OR 4.11, p=0.002 for hospitalization), systemic sclerosis diagnosis (OR 3.45, p=0.03 for Covid-19 severity) and myositis diagnosis (OR 4.91, p=0.033 for hospitalization) were associated with worse Covid-19 outcomes. On the other hand, spondyloarthropathies appear to be negatively associated with Covid-19 severity (OR=0.27, p=0.035).ConclusionAccording to our study, most ARD patients recovered uneventfully from Covid-19. However, there are several indications that we should be vigilant for patients who remain unvaccinated, are older, have a systemic sclerosis or myositis diagnosis, and/or receive intense immunosuppressive regiments such as rituximab.References[1]Papagoras C, Fragoulis GE, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2021 Nov 10.[2]Strangfeld A, Schäfer M, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.Table 1.N=209ARD Diagnosisn (%)Rheumatoid arthritis34 (16.3)Seronegative spondyloarthropathies60 (28.7)Systemic lupus erythematosus45 (21.5)Systemic sclerosis24 (11.5)Sjogren's syndrome15 (7.2)Vasculitis19 (9.1)Myositis9 (4.3)Other3 (1.4)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

THE IMPACT OF IMMUNOMODULATING TREATMENT ON THE SEROLOGICAL IMMUNOGENICITY FOLLOWING THREE DOSES OF COVID-19 VACCINE AND PERSISTENCE OF IMMUNOGENICITY OF TWO VACCINE DOSES IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES - A SWEDISH STUDY (COVID19-REUMA)

BackgroundData on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.ObjectivesTo elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.MethodsAntibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.ResultsIn total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118;68% female;mean age 67 years), abatacept (n=18;72% female;mean age 64 years), IL6r inhibitors (n=60;73% female;mean age 64 years), JAK-inhibitors (n=44;80% female, mean age 52 years), TNF-inhibitors (n=59;70% female;mean age 47 years;), IL12/23/17 inhibitors (n=24;46% female;mean age 54 years) and controls (n=36;75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.ConclusionIn this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.Figure 1.AcknowledgementsThe study has been supported by the independent research grants from Roche.Disclosure of InterestsMartina Frodlund: None declared, Per Nived: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Grant/research support from: Research grand from Galapagos, Anna ödergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Lars Klareskog: None declared, Meliha C Kapetanovic Grant/research support from: independent research grants från Pfizer and Roche.

COVID-19 CHALLENGE IN THE ANTIPHOSPHOLIPID SYNDROME – AN OBSERVATIONAL STUDY OF A SERBIAN COHORT

BackgroundFacing the outburst of the COVID-19 pandemic, we gradually comprehend its pathophysiology as a coagulopathy characterized by increased risks of arterial, venous, and microvascular thrombosis. Antiphospholipid syndrome (APS) is an autoimmune, thrombo-inflammatory disease characterized by thrombosis and/or pregnancy loss in the presence of one or more antiphospholipid antibodies (aPL).ObjectivesTo evaluate the clinical scenario of COVID-19 in the APS population of patients.MethodsThis is a single-center, observational, cross-sectional study. Data regarding the severity of COVID-19 (severe COVID-19 considered if interstitial pneumonia was diagnosed), COVID-19 vaccinal status, and post-vaccinal reactions (divided into mild, consisting of fever, myalgia, nausea, and severe if thrombosis at any point occurred) were collected from 44 APS patients (21 with primary and 23 with APS associated with systemic lupus erythematosus (SLE), 90.1% female). aPL analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA Results were compared to the control group consisting of 31 healthy individuals, with no APS, matched to the APS group regarding age and gender.ResultsAt the moment of COVID-19 infection, 75% of the APS group was taking Aspirin, 15.9% warfarin, 2.3% non-vitamin K oral anticoagulant, 59.1% chloroquine, 31.8% corticosteroid, 2.3% methotrexate. None of the above-mentioned medications were taken from a control group. There was no difference regarding the severity of COVID-19 between APS patients and healthy controls: 84.1% of APS had mild and 15.9% severe COVID-19 (p=0.509, p=0.292 respectively). But the difference regarding the need for hospitalization was significant (none of the healthy controls compared to 11.4% APS patients, p=0.0073). Interestingly, COVID-19 occurred in 72.7% of APS patients before the COVID-19 vaccination compared to 35.5% of healthy controls, p=0.001, conversely, a significantly lower percentage of vaccinated APS patients had COVID-19 compared to healthy controls (34.1% to 71.0%, p=0.002). 27% of APS patients had mild post-vaccinal reactions, none with severe.ConclusionDuring the COVID-19 pandemic, APS patients in Serbia were at higher risk for hospitalization. However, there was no difference in the severity of clinical presentation compared to non -the APS population. We can only speculate that APS therapy consisting of Aspirin, Chloroquine, and oral anticoagulant therapy contributed to this finding. Moreover, COVID-19 vaccination in the APS population, followed by a low incidence of mild post-vaccinal reactions, had more benefits in protection than in non-APS individuals.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

DO PATIENTS ON SUPPRESSIVE THERAPY HAVE A DECREASED HUMORAL RESPONSE TO SARS-CoV2 VACCINATION?

BackgroundSARS-Cov2 vaccination has been shown to be effective against severe forms of SARS-Cov2 infection. Several studies investigated the humoral and cellular response to SARS-Cov2 vaccines in patients followed for autoimmune and inflammatory diseases under immunosuppressive or immunomodulatory treatments. It has been shown that patients on immunosuppressive or immunomodulatory therapies have a poor humoral response to the vaccine[1]ObjectivesThe aim of our study was to investigate the humoral response in patients under conventional immunosuppressive and biotherapies compared to healthy controls.MethodsPatients followed for immuno-inflammatory diseases under immunosuppressive or immunomodulatory drugs who received at least one dose of anti- SARS-Cov2 vaccines were included. Quantitative Anti- SARS-Cov2 antibodies (IgM and IgG assay) VIDAS ® were assessed for all patients. Patients were then compared with healthy controls.ResultsWe enrolled 93 blood samples (63 patients with autoimmune and inflammatory disease and 30 healthy controls), the median age was 52 years [Q1 43, Q3 56]. The immuno-inflammatory diseases were: Crohn's disease (n=28), Rheumatoid arthritis (n=9), Hemorrhagic rectocolitis (n=5), Behçet's disease (n=5), Systemic lupus erythematosus (n=4), Sjogren's syndrome (n=3), Sarcoidosis (n=2), Takayasu disease (n=1). All patients continued their treatment during and after vaccination. Nineteen patients were on biotherapies: Infliximab (n=12), Adalimumab (n=3), etanercept (n=2), Ustekinumab (n=1), tocilizimab (n=1). Forty-three patients were on conventional immunosuppressive: azathioprine (n=18), methotrexate (n=16), corticosteroids > 10 mg/d (n=12). All patients had received at least one dose of vaccine: the median number of doses in both groups was 2[1-4] with no statistically significant difference between the 2 groups (p=0.2). The vaccines received in the group of patients were mRNA vaccine (n=35) and other type of vaccine (n=28). In the healthy control group, type of vaccine were mRNA (n=13) other type vaccine (n=17). The patient had a lower mean level of Ig G against SARS-Cov2 antibodies (24.64 IU +/- 16.65) comparing to healthy controls (33.05+/- 10) with statically significant difference (p= 0.014). No difference between the 2 groups was noted in Ig G levels according to the history of SARS-Cov2 infection. No difference was found between conventional immunosuppressive drugs and biotherapies regarding to the level of antibodies.ConclusionOur study highlights that patients with autoimmune disease and under immunosuppressive therapy displayed a decrease of humoral response comparing to healthy controls. This finding was reported in several studies, Geisen et al[2] reported that patients with chronic inflammatory condition and receiving TNF alfa blockers had a decreased protection and a low level Ig A against spike. Based on these data, patients with autoimmune and inflammatory diseases have decreased humoral immunity to SARS-Cov2 and should be encouraged to receive a booster dose of SARS-COv2 vaccine.References[1]Prendecki M, Clarke C, Edwards H, et al. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression. Ann Rheum Dis 2021;80:1322–9. doi:10.1136/annrheumdis-2021-220626[2]Geisen UM, Sümbül M, Tran F, et al. Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies. RMD Open 2021;7:e002008. doi:10.1136/rmdopen-2021-002008AcknowledgementsMrs Hajer Mediouni.Disclosure of InterestsNone Declared.

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

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

CELLULAR AND HUMORAL IMMUNOGENICITY OF THE NEOANTIGEN S1 FROM SARS-COV-2 VACCINES IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES

BackgroundData on cellular and humoral immunogenicity triggered by SARS-CoV-2 vaccines in patients with autoimmune rheumatic diseases (ARDs) are limited. While current vaccine efforts have focused on the induction of neutralizing antibodies against SARS-CoV-2, T-cell immunity may also provide protection against infection. Experimental data suggest that CD8+ T cell responses may have a protective role in the presence of decreasing or sub protective antibody titers [1].ObjectivesThe aim of this project is to describe the serological and T cell responses to the third dose of vaccine (either with BNT162b2 mRNA or ChAdOx1 nCoV-19 replication-deficient adenoviral vector vaccines) in a cohort of patients with ARDs (rheumatoid arthritis and spondyloarthropathies) treated with biologic therapies, to describe the impact of these treatments on vaccine response in this patient population. As a second objective, we will describe the characteristics of patients who did not present an adequate immunogenic response.MethodsCase-control study. We studied in 79 patients with ARDs and in 31 healthy controls, anti-SARS-CoV-2 specific interferon-gamma (IFN-γ) production measured by IGRA between 8-12 weeks after the third dose of anti-SARS-CoV-2 vaccine. In addition, humoral response was measured by anti-S1 IgG antibody production measured by chemiluminescent microparticle immunoassay. Statistical comparison between categorical variables was performed by Fisher's or χ2 test. For quantitative variables by Kruskal-Wallis test or Mann-Whitney test.Results79 patients with ARDs (48 women, 31 men;mean age 58±11.4) 43 (54%), with rheumatoid arthritis and 36 (45.6%) with spondyloarthropathies. 32 (49.5%) of them were on glucocorticoid treatment (mean dose 4.92 mg/day), 25 (31.6%) on methotrexate and 56 (70.9%) on anti-TNF. Post-vaccination results showed positive T-cell immune responses in 68 of 79 (86.1%) ARDs patients with mean IFN- γ anti-SARS-CoV-2 titers of 1,606.85 mUI/ml. 7 (8.9%) of ARDs patients showed negative IFN-γ SARS-CoV-2 levels, while 4 (5%) had borderline titers. 100% of patients with previous COVID 19 disease had positive cellular responses. Within the group of negative or borderline cellular responses, 7 of 10 were men (70%), with no significant differences in terms of diagnosis, comorbidities or immunosuppressive treatments used. In the control group, 100% presented positive cellular responses. Anti-Spike IgG antibodies were detectable in all patients with ARDs as in the control group.ConclusionOur preliminary data show that most patients with ARD were able to generate an adequate specific cellular response after vaccination against SARS-CoV-2, emphasizing the relevance of vaccination in this group. Specific antibody responses secondary to anti-SARS-CoV-2 vaccination were detected in all patients with ARD. Our data could support the relevance of these immune responses to personalize prevention, vaccination decision-making and treatment in this subgroup of patients.References[1]Sieiro Santos C, Calleja Antolin S, Moriano Morales C, Garcia Herrero J, Diez Alvarez E, Ramos Ortega F, et al. Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases. RMD Open. 2022 Jan 5;8(1).Figure 1.Specific anti-SARS-CoV-2-IFN- γ responses measured by IGRA. Dotted lines represent positivity cut-off: ≥200mUI/ml. HC: Healthy controls. AIRDs: Autoimmune rheumatic diseases.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsNone Declared.

OUTCOME FOR PATIENTS WITH GIANT CELL ARTERITIS (GCA) TREATED WITH TOCILIZUMAB ACCORDING TO NICE GUIDANCE IN A SINGLE TERTIARY UK CENTRE

BackgroundIn 2018 NICE and NHS England approved one year of weekly subcutaneous tocilizumab for use in relapsing or refractory GCA [1, 2]. During the COVID pandemic NHS England allowed extended use of tocilizumab in selected high risk patients [3]. This extension ended in March 2022. This has created a cohort of patients who are now no longer treated with tocilizumab and may be at risk of GCA flare. Currently, NHS England does not allow retreatment with tocilizumab.ObjectivesThis service evaluation used an intention-to-treat approach to retrospectively evaluate patients, who were ratified to receive tocilizumab for GCA according to the NICE guidance. We aimed to describe this cohort of patients for whom the use of tocilizumab had been approved, and their outcomes in terms of complications and disease control.Methods49 patients were ratified to receive tocilizumab between May 2019 and April 2022 by a specialist multidisciplinary team at a single tertiary rheumatology center. Their response was assessed in terms of relapse rates, steroid usage and complications as described below.Results80% of the 49 cohort of patients consisted of females (Table 1). 55% of patients were diagnosed with GCA on combination of clinical history, laboratory and temporal artery duplex findings. 94% (46/49) had at least a week's course of tocilizumab. Around half (51%) had relapsing disease. 6% had first dose as intravenous due to critical ischaemia. 27% (13/49) of patients developed complications whilst on treatment. Six developed cytopenia, 3 acquired infections and 4 stopped due to other reasons. As per guidelines, tocilizumab was stopped after 12 months in 25 patients (51%). 16% stopped treatment early due to complications. 18% had incomplete information. 10% had ongoing treatment. One patient died several months after finishing tocilizumab. 47% had methotrexate as DMARD therapy added prior to tocilizumab commencement (Figure 1). Out of 25 patients who completeted treatment, 24% (6/25) relapsed. 83% of these relapses were diagnosed on recurrence of symptoms and high inflammatory markers. In addition, 3 patients, who had tocilizumab suspended relapsed. 2/3 of these patients had treatment suspended due to infection. 5/9 relapse patients did not have preceding DMARD therapy. 22% (2/9) of relapse patients had PET-CT due to involvement of extra-cranial disease. 56% (5/9) relapsed following a median follow-up of 11 months. Of relapsed patients, seven were treated with increased dose of prednisolone and two patients received 6 months extension of tocilizumab with adequate tolerance and efficacy.ConclusionOur data shows good tolerability of tocilizumab and a 24% flare rate amongst patients who completed treatment. This is less than the 50% rate seen in GiACTA and other cohorts, where the majority of which occurred within 6 months of stopping treatment [4]. DMARD treatment may reduce relapse rate, but this will require further study. The data describing the efficacy of treatment beyond one year is limited [3]. However, with no established guidance for treating patients following tocilizumab, extension of treatment is a plausible option.References[1]Tocilizumab for treating giant cell arteritis, NICE Technology Appraisal Guidance, 18 April 2018. https://www.nice.org.uk/guidance/ta518/resources/tocilizumab-for-treating-giant-cell-arteritis-pdf-82606786726597[2]Stone J, Tuckwell K, Dimonaco S et al.Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377:317-328.[3]Regola F, Cerudelli E,Bosio G. Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients Rheumatology Adv Pract 2020;0:1–9.[4]Conway R, Putman MS, Mackie SL. Benchmarking tocilizumab use for giant cell arteritis. Rheumatol Adv Pract. 2022;6(2):rkac037.Figure 1.Table 1.GenderAge at time of diagnosisIndication for stopping treatmentMaleFemale50-5960-6970-7980-89Completed treatmentComplicationsOngoing treatmentIncomplete information18313162010251058Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Health is complex, the solutions are long term

The debate on folic acid fortification of food to prevent neural tube defects in babies, for example, hasn't progressed in more than two decades (doi:10.1136/bmj.p1158).8 The worrying rise in perinatal suicides requires better funded services and support for women and young families to prevent deaths (doi:10.1136/bmj-2023-075414).9 And are the mandatory school inspections that harm the mental health of teaching staff even necessary (doi:10.1136/bmj.p1147)?10 The same applies to overzealous and discriminatory processes implemented by medical regulatory bodies such as the General Medical Council, despite claims of improvement by its chief executive (doi:10.1136/bmj.p1295 doi:10.1136/bmj.p1252).1112 The prevention principle would urge us to support a ban on vaping (doi:10.1136/bmj.p1266) and consider new options for reducing the number of days people experience migraines (doi:10.1136/bmj.p1249).1314 It would also induce bewilderment at the decision to wind down the UK's world leading covid surveillance network when covid-19 is still with us and future pandemics are inevitable (doi:10.1136/bmj.p1157).15 It would not, however, lend support to a non-evidence based screening programme for haemochromatosis (doi:10.1136/bmj.p1264).16 The first steps of an "avoid, reduce, reuse, recycle, research, rethink” framework (doi:10.1136/bmj-2021-069044) focus on better clinical practice that avoids low value care and inappropriate admissions and minimises blood tests and other interventions.17 This latest article in our series on achieving net zero and environmental sustainability in clinical practice examines critical care. The challenge isn't entirely a clinical one, because achieving net zero will depend on commitment across healthcare professions, engineering, waste management, hospital leadership, and beyond. A research paper assessing the value of routine monitoring of people being treated with methotrexate finds that frequency of monitoring should be adjusted according to risk, reducing the burden of work on clinical staff and making life more manageable for patients (doi:10.1136/bmj-2022-074678 doi:10.1136/bmj.p1120).1819 The difficulty here is one of getting research into practice, a timescale of 17 years by some estimates.

DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action.

During the COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Based on previous data on methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly attributed to the intrinsic anti-metabolic activity of these drugs, but also to a specific anti-viral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, pralatrexate and trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.