Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

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

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

CHARACTERISTICS OF PATIENTS WHO RECEIVED BIOLOGICAL TREATMENT AFTER KIDNEY TRANSPLANTATION AND THE INCIDENCE OF SERIOUS INFECTIONS: A MULTICENTER STUDY

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.

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

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

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.

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

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

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.

Immunosuppressant Drugs and Covid-19: Associated Risks, Drug-Drug Interactions and Contraindications

Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclos-porine, and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase mortality and morbidity, as a weakened immune system can lead to a longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and their associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organization), U.S FDA (Food and Drug Administration), and other accredited global health organizations. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications, and drug-drug interactions. Our study will help government partners and international health organizations to understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised, and organ transplant patients will help lower the mortality and morbidity associated with the disease amid the COVID-19 pandemic.Copyright © 2021 Bentham Science Publishers.

Cancer, Covid and Control of Ra - a Toxic Combination?

Case report - Introduction: This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with highdose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description: A is a 67-year-old female nonsmoker diagnosed with seropositive rheumatoid arthritis (RF, anti - CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5-10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion: Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theo etical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points: . Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers - lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult.

Pharmacological treatment of COVID-19: an opinion paper.

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes

PURPOSE OF THE STUDY: Given the similarities between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki's disease, most patients with MIS-C have been treated with intravenous immune globulin (IVIG), the standard of care for Kawasaki's disease. However, other immunomodulatory therapies, including corticosteroids and biologics, have been used to counter the cytokine-related inflammatory changes in MIS-C. The purpose of this study was to describe the pattern of immunomodulatory therapies used in patients with MIS-C in the United States and to assess the relative effectiveness of IVIG plus corticosteroids (CSTs), compared with IVIG alone, in the initial treatment of MIS-C. STUDY POPULATION: The Overcoming COVID-19 surveillance registry identified 596 patients as having MIS-C at each of the 58 participating hospitals between March 15 and October 31, 2020. Of these, 518 (87%) were flagged as receiving at least 1 immunomodulatory treatment. The researchers then analyzed longitudinal data collected in this cohort, including demographic characteristics, underlying medical conditions, signs and symptoms at presentation, clinical course, laboratory test results, diagnostic studies, treatments, complications, and outcomes. METHODS: Statistical comparisons between IVIG+CSTs and IVIG treatment groups were done by population sampling using propensity score matching;among the patients treated with IVIG plus glucocorticoids or IVIG alone on day 0, a total of 206 could be matched at a 1:1 ratio and based on propensity scores. To compare the potential effectiveness of initial immunomodulatory treatment, the authors prespecified a primary composite outcome of cardiovascular dysfunction (left ventricular ejection fraction < 55% and/or shock needing vasopressor support) on day 2 or beyond, up until discharge. Secondary outcome measures included the primary outcome components, escalation of immunomodulation treatment after day 1, and recurrent or persistent fever on day 2 and beyond. The potential effectiveness of treatment in primary and secondary outcomes was also assessed using an inverse-probability weighted analysis. RESULTS: Of the patients treated, 241 (47%) received IVIG and CSTs;107 (21%) received IVIG, CSTs, and a biologic (anakinra, etanercept, infliximab, or tocilizumab);89 (17%) received IVIG only;and 81 (16%) received other treatments, including CSTs only, a biologic only, CSTs and a biologic, or IVIG and a biologic. Highest illness severity was seen in the 107 patients who received IVIG, CSTs, and a biologic combined. Treatment patterns changed over time, with an observed decrease in the fraction of cases treated with IVIG alone, offset primarily by an increase in the use of IVIG with CSTs together. In the propensity-score-matched analysis, initial treatment with IVIG + CSTs was associated with a lower risk of cardiovascular dysfunction and less escalation of immunomodulatory treatments later in hospitalization, but the risks of persistent or recurrent fever and length of stay in the ICU were not clearly lower. The inverse-probability-weighted analysis confirmed the findings of the propensity-score-matched analysis. CONCLUSIONS: The authors found that initial treatment with IVIG plus glucocorticoids for MIS-C was associated with a lower risk of cardiovascular dysfunction than initial treatment with IVIG alone.

Challenges of COVID-19 in Rheumatic Autoimmune Diseases (RADs) Patients

Upon COVID-19 infection, age-specific mortality rates in RADs patients notably began from 35 years old, while in the uninfected population, it was from 55. COVID-19 associated rheumatic signs and symptoms are myalgia, fatigue, Kawasaki-like signs, and skin rashes mimicking vasculitides and pernio (chilblains) like lesions. So a variety of rheumatic diseases may mimic or be mimicked by COVID-19. Rheumatologic Treatments During COVID-19 Epidemic: Prednisone caused an increased hospitalization rate, significantly when the dose exceeded 10 mg per day. It is reasonable to reduce glucocorticoids gradually to 5 - 7.5 mg/day, but discontinuation during the pandemic is not recommended. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) reduce the risk of COVID-19 infection and the cytokine storm emerging in severe cases. Colchicine has reduced the mortality of COVID- 19 patients and the number of severe cases. Tapering or even discontinuing csDMARDs is suggested to recover immunity in severe cases, which may help rapidly eliminate the virus. Hydroxychloroquine is likely to increase survival in SLE patients, and it is not advisable to be discarded. Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) may help reduce inflammatory cytokine storm under COVID-19 attack. Compared with RADs patients treated with CD20 monoclonal antibody rituximab or IL-17A antagonist secukinumab, patients receiving tumor necrosis factor (TNF) inhibitors etanercept and alemtuzumab or IL- 6 receptor antagonist tocilizumab may experience milder course. Applicable Laboratory Indicators: Elevation of ESR, CRP, ferritin, interleukin 6, and creatine kinase can be seen in COVID-19 and various rheumatic diseases. RADs related autoantibodies may present among non-RAD severe COVID- 19 cases. COVID-19 as a Risk Factor for Rheumatologic Diseases: Cases of Small vessel cardiac vasculitis/endothelium, immunoglobulin A (IgA) vasculitis in patients with Crohn disease, cutaneous vasculitis-like lesions, systemic arterial and venous thromboembolism including cryptogenic strokes and other vasculopathy features, systemic rheumatic diseases such as SLE, inflammatory arthritis, GCA, inflammatory myopathies, APS, Sjogren's syndrome, ANCA-associated vasculitides, seropositive rheumatoid arthritis, and Virus-associated or reactive arthritis and Crystal-related arthritis due to gout or calcium pyrophosphate disease has been reported. COVID-19, in the acute phase, may cause cytokine storm and severe inflammatory response;and in the chronic phase, patients become susceptible to autoinflammatory and autoimmune diseases. If a patient has signs and symptoms of rheumatic diseases after developing COVID-19, do not attribute these complaints entirely to COVID-19;consider starting a real dangerous rheumatic disorder.

LUNG INVOLVEMENT in VEXAS SYNDROME

Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.

EVALUATION of the SAFETY PROFILE of COVID-19 VACCINES in CHILD PATIENTS USING BIOLOGICAL THERAPY

Background: Coronavirus vaccines have been widely applied all over the world after the coronavirus pandemic. There are inactivated vaccines and mRNA vaccines in our country. There is no clear guideline for the vaccination programs of patients receiving immunosuppressive therapy, especially childhood. Objectives: For this reason, we wanted to evaluate the frequency of side effects developed after covid-19 vaccine in pediatric patients diagnosed with rheumatic disease using biological therapy and nonbiologic disease modifying drugs Methods: A total of 226 patients over the age of 12, who were followed up in the pediatric rheumatology clinic of the University of Health Sciences, Umraniye Training and Research Hospital, using biological therapy and were vaccinated against Covid-19, were included in the study. The standard questionnaire forms were flled in face-to-face after each administration for both vaccines. The patient, who had any serious side effects, was followed up in the hospital. Results: Of the 226 patients included in the study, 97 were male and 128 were female. Their mean age was 16.4 + 2.4. It was determined that 88.4% (n=200) of the patients had mRNA vaccine and 11.6% (n=26) had inactivated vaccine. 105 of the patients were using biologic drugs during vaccination. Of these, 63 (27.9%) patients were treated with anti-TNF drugs (46 adalimumab, 10 etanercept, 6 infix-mab), 32 patients were anti-il-1 (30 canakinumab, 2 anakirna), 4 patients were anti-il-6, 3 patients were anti-il-17, 3 patient was receiving abatacept and 1 patient was receiving rituximab. 121 patients were using DMARDs. Of these, 61 were using colchicine. 26.5% (n=60) of the patients had covid infection before vaccination. Side effects were observed in 180 of our patients. No side effects were observed in 46 patients. Pain at the injection site was the most common among them, 72.6% (n=164). Headache was seen in 16.8% (n=38) of the patients, myalgia in 18.1% (n=41), fever in 16.4% (n=37) and arthralgia in 6.6% (n=15). The frequency of serious adverse events was determined as 0.9%(n=2). Both patients were followed up in the ward. When the patients were compared in terms of covid infection and gender, there was no signifcant difference in the frequency of side effects. When the vaccines were compared, the incidence of side effects in the mRNA vaccine was statistically signifcantly higher (p=0.001). Pain at the injection site was signifcantly less frequent in the inactivated vaccine (p=0.004). In terms of drug distribution, there was no signifcant difference in the frequency of side effects between patients using biologic drugs and DMARDs. p=0.004) There was no statistically signifcant difference in the frequency of side effects when the patients using dmard were compared as colcicine and other dmards. Conclusion: In our study, we have shown that the use of vaccines in individuals with adolescent rheumatological diseases is safe and that the biological treatments used by the patients do not cause an increase in the risk of vaccine side effects. In addition;We have shown in our study that the side-effect profile of the inactivated vaccine used in our country is milder than the mRNA vaccine, and that it affects daily life less. Another result of our study was that anti-TNF drugs could cause a decrease in pain sensation due to the relationship of anti-TNF with pain pathways.

IMPACT of SARS-COV-2 INFECTION on the DISEASE ACTIVITY of PATIENTS with PSORIATIC ARTHRITIS under BDMARDS: REAL LIFE DATA

Background: SARS-CoV-2 infection can lead to severe infammation and has been suggested to induce Psoriatic Arthritis (PsA) fares.1 However, the impact on disease activity and response to biological disease modifying anti-rheumatic drugs DMARDs (bDMARDs) remains unknown. Objectives: To evaluate the effect of SARS-CoV-2 infection on disease activity and bDMARDs responses in patients with PsA. Methods: We performed a retrospective analysis including all the patients with PsA, meeting the CASPAR criteria and under biologic therapy, followed in the Rheumatology department of a tertiary university hospital. Demographic and clinical data, including occurrence of SARS-CoV-2 infection, were collected from our national database (reuma.pt). Disease activity (CDAI, SDAI, DAS28 4v, BASDAI, ASDAS) and bDMARDs responses (EULAR, ASDAS, ASAS, ACR and PsARC responses) were evaluated before and after SARS-Cov-2 infection. Statistical analysis was performed with SPSS. Continuous variables were compared through paired samples t-test. Results: A total of 102 patients with PsA were included. Fifty-two were females (51%).The mean age was 53 ± 11.09 years and the median disease duration was 15 years [min 2, max 47]. Overall, 54 (53%) patients had predominant axial involvement, 26 (26%) peripheric and 36 (37%) enthesopathic. The most used bDMARD was etanercept (n=28, 27.5%) followed by adalimumab (n=22, 21.6%) and secukinumab (n=18, 17.6%). The prevalence of SARS-CoV-2 infection was 15.7% (n=16). Sixty-three per cent received the BNT162b2 (Pfzer/BioNtech) vaccine, 31% received mRNA-1273 (Moderna), 13% received AZD1222 (AstraZeneca) and 13% received AD26. COV2.S (Janssen/Johnson & Johnson). Sixty-three percent were infected before any vaccination, 13% after the frst dose and 25% after the second. The most common symptoms were anosmia (65%), dysgeusia (56%) and cough (56%). All patients fully recovered from the infection, with no need for hospitalization. Regardless of the score used, the difference between the mean disease activity after SARS-CoV-2 infection and that at baseline did not reach statistical significance. At baseline and after infection, mean (SD) disease activity parameters were, respectively: CDAI 8.6±5.7 vs 8.6±5.7, p=0.997;SDAI 9.3±6.6 vs 9.2±6.1, p=0,928;DAS 28 4v 2.9±1.2 vs 2.9 ±1.2, p= 0.818;BASDAI 3.6 ±2.6 vs 3.2±2.7, p=0.506;ASDAS 2.2±1.2 vs 2.2±1, p=0.721. The number of patients unresponsive to bDMARDs (according EULAR, ASDAS, ASAS, ACR and PsARC) before the infection wasn't different from post-infection. Conclusion: Our study suggests that SARS-CoV2 infection has no negative impact on PsA disease activity and bDMARD responses. However, more studies are still needed to better understand the long-term effects of SARS-CoV2 infection.

THE IMPACT of COVID-19 on MEDICATION NON-ADHERENCE in A RHEUMATOID and PSORIATIC ARTHRITIS UK COHORT

Background: In March 2020, as part of the UK's COVID-19 prevention strategy, those identifed as 'clinically extremely vulnerable,' were advised to shield. This included a number of patients prescribed anti-rheumatic drugs, who were asked to continue their current treatment unless they developed symptoms of infection. Suboptimal treatment adherence (16.0%-81.0%) has been reported in patients with arthritic diseases, and is associated with psychological factors, including anxiety (1). Previous literature in non-UK cohorts has highlighted suboptimal adherence levels in immunosuppressed patients during the pandemic, although many were single centre studies (2,3). Objectives: The aim of this multi-centre study is to investigate the impact of the COVID-19 pandemic on adherence to anti-rheumatic medications in patients with established rheumatoid (RA) and psoriatic (PsA) arthritis in the UK who had recently commenced a biologic or targeted synthetic DMARD. Methods: Between September 2020 and May 2021, RA and PsA patients prescribed biologic or targeted synthetic anti-rheumatic drugs from two multi-centre observational studies (BRAGGSS and OUTPASS) were sent a questionnaire on medication usage, adherence, and perceptions to establish the impact of COVID-19 on these parameters. Patients were asked about compliance during the COVID-19 pandemic using a 5-point Likert scale (always, often, sometimes, rarely, and never) and the reason for non-adherence. Adherence was defned as never missing or delaying a dose, unless medically advised. Descriptive summary statistics were calculated, and logistic regression and Pearson's chi-squared tests were employed to investigate variables associated with self-reported non-adherence. Results: In total 159 questionnaires were returned (81.1% RA and 18.9% PsA). Methotrexate (53.5%) was the most frequently prescribed agent, followed by etan-ercept (25.2%), sulfasalazine (22.6%), hydroxychloroquine (21.4%) and adalimumab (19.5%). Furthermore, 68.6% of patients were prescribed ≥2 drugs. During the pandemic, 42.1% of patients reported missing or delaying a treatment dose for any reason. Adherence information was available for 97.5% of patients with 25.8% reporting non-adherence which was not medically advised. Methotrexate non-adherence was 27.1%, with similar levels reported for etanercept (20.0%), sulfasalazine (27.8%), hydroxychloroquine (35.3%) and adalimumab (29.0%). No drugs had signifcantly different adherence compared to methotrexate. Furthermore, there was no association between disease type or perception of disease control and adherence. Of non-adherent patients, 17.5% reported increased anxiety, fear, and increased risk due to the COVID-19 pandemic as an influencing factor. Meanwhile, 37.5% of non-adherent patients listed non-COVID-19 intentional reasons and 45.0% reported non-intentional reasons, with forgetting and running out of treatment listed most frequently. Conclusion: In a UK cohort self-reported non-adherence was reported in 25.8% of patients during the COVID-19 pandemic, despite medical advice, with reasons including increased anxiety due to COVID-19.

COVID-19 in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES-DATA from the ROMANIAN REGISTRY of RHEUMATIC DISEASES

Background: Registries are providing real-life, long-term data relevant to safety, efficacy and long-term outcomes in patients with various rheumatic diseases. The Romanian Registry of Rheumatic Diseases (RRBR) collects efficacy and safety data, for patients with infammatory rheumatic conditions treated with bio-logics and targeted synthetic DMARDs in the country. Infections are the most frequently adverse events associated with biologics exposure. Objectives: To analyze the distribution, severity class and outcome of infection with SARS-CoV-2 in infammatory arthritides during the last 2 years of COVID-19 pandemic. Methods: We collected data for the past 2 years (2020 and 2021) from the RRBR, for the three main infammatory rheumatic diseases (Rheumatoid Arthritis-RA, Spondyloarthritis-SpA and Psoriatic Arthritis-PsA): treatment exposure (drug class) at the time of COVID-19 diagnosis, severity class (mild, moderate, severe), the disease outcome (recovered, disabled, death). Finally, we compared those data to reported numbers of COVID-19 infections in the general population, aiming to observe if there is a signifcant difference between the two groups. Results: The study included 9469 patients with infammatory rheumatic disease, in 298 (3.14%) patients a history of COVID-19 infection was recorded: 160 (53.69%) were diagnosed with RA, 116 (38.92%) with SpA and 22 (7.28%) with PsA. At the moment of COVID-19 infection, 200 patients were receiving anti-TNF inhibitors (67.11%), 27 JAK inhibitors (9.06%), 24 tocilizumab (8.05%), 23 rituximab (7.71%), 9 anti-IL17A monoclonal antibodies (3.02%) and 4 abat-acept (1.34%). More than half of the cases were mild-59.39% (177), whereas moderate forms were noted in 26.17% (78) and severe in 14.09% (42) of the total infected patients. Out of the 42 severe COVID-19 cases, 11 (26.19%) were treated with rituximab, 18 (42.85%) with TNF inhibitors, 7 (16.66%) with JAK inhibitors, 4 (9.52%) with tocilizumab, 1 (2,38%) with secukinumab and 1 (2.38%) with abatacept. Almost all cases recovered: 286 (95.97%) patients, while 12 (4.02%) deaths were recorded. The patients who died were on treatment with rituximab (5), tofacitinib (3), etanercept (2), secukinumab (1) and tocilizumab (1). Data from the National Public Health Institute showed a rate of COVID-19 infection in the general population of 9.36%, out of which 96.7% had a favorable outcome, while 3.26% deaths were reported. Conclusion: This study confrms that patients receiving treatment with rituxi-mab are at risk for a worse COVID-19 outcome. The increased number of severe cases and deaths related to COVID19 in patients receiving TNF inhibitors may be explained by the large use of this therapeutic option. Surprisingly, we noted 4 severe cases and one death related to COVID19, in patients treated with tocilizumab. We observed no signifcant differences in death rates and the outcomes of COVID-19 in patients with rheumatic diseases treated with biological therapies and the general population. The low rate of SARS-CoV-2 reported infections in the registry, compared to the general population, is most probably due to the commonly found underreporting of adverse events in registries.