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.

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.

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

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

CHARACTERISTICS ASSOCIATED with POOR COVID-19 OUTCOMES in PEOPLE with PSORIASIS and SPONDYLOARTHRITIS: DATA from the COVID-19 PSOPROTECT and GLOBAL RHEUMATOLOGY ALLIANCE PHYSICIAN-REPORTED REGISTRIES

Background: Some factors associated with severe COVID-19 outcomes have been identifed in patients with psoriasis (PsO) and infammatory/autoimmune rheumatic diseases, namely older age, male sex, comorbidity burden, higher disease activity, and certain medications such as rituximab. However, information about specifcities of patients with PsO, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), including disease modifying anti-rheumatic drugs (DMARDs) specifcally licensed for these conditions, such as IL-17 inhibitors (IL-17i), IL-23/IL-12 + 23 inhibitors (IL-23/IL-12 + 23i), and apremilast, is lacking. Objectives: To determine characteristics associated with severe COVID-19 outcomes in people with PsO, PsA and axSpA. Methods: This study was a pooled analysis of data from two physician-reported registries: the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), comprising patients with PsO/PsA, and the COVID-19 Global Rheumatology Alliance (GRA) registry, comprising patients with PsA/axSpA. Data from the beginning of the pandemic up to 25 October, 2021 were included. An ordinal severity outcome was defned as: 1) not hospitalised, 2) hospitalised without death, and 3) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics (age, sex, time period of infection), comorbidities (hypertension, other cardiovascular disease [CVD], chronic obstructive lung disease [COPD], asthma, other chronic lung disease, chronic kidney disease, cancer, smoking, obesity, diabetes mellitus [DM]), rheumatic/skin disease (PsO, PsA, axSpA), physician-reported disease activity, and medication exposure (methotrexate, lefunomide, sulfasalazine, TNFi, IL17i, IL-23/IL-12 + 23i, Janus kinase inhibitors (JAKi), apremilast, glucocorticoids [GC] and NSAIDs). Age-adjustment was performed employing four-knot restricted cubic splines. Country-adjustment was performed using random effects. Results: A total of 5008 individuals with PsO (n=921), PsA (n=2263) and axSpA (n=1824) were included. Mean age was 50 years (SD 13.5) and 51.8% were male. Hospitalisation (without death) was observed in 14.6% of cases and 1.8% died. In the multivariable model, the following variables were associated with severe COVID-19 outcomes: older age (Figure 1), male sex (OR 1.53, 95%CI 1.29-1.82), CVD (hypertension alone: 1.26, 1.02-1.56;other CVD alone: 1.89, 1.22-2.94;vs no hypertension and no other CVD), COPD or asthma (1.75, 1.32-2.32), other lung disease (2.56, 1.66-3.97), chronic kidney disease (2.32, 1.50-3.59), obesity and DM (obesity alone: 1.36, 1.07-1.71;DM alone: 1.85, 1.39-2.47;obesity and DM: 1.89, 1.34-2.67;vs no obesity and no DM), higher disease activity and GC intake (remission/low disease activity and GC intake: 1.96, 1.36-2.82;moderate/severe disease activity and no GC intake: 1.35, 1.05-1.72;moderate/severe disease activity and GC intake 2.30, 1.41-3.74;vs remission/low disease activity and no GC intake). Conversely, the following variables were associated with less severe COVID-19 outcomes: time period after 15 June 2020 (16 June 2020-31 December 2020: 0.42, 0.34-0.51;1 January 2021 onwards: 0.52, 0.41-0.67;vs time period until 15 June 2020), a diagnosis of PsO (without arthritis) (0.49, 0.37-0.65;vs PsA), and exposure to TNFi (0.58, 0.45-0.75;vs no DMARDs), IL17i (0.63, 0.45-0.88;vs no DMARDs), IL-23/IL-12 + 23i (0.68, 0.46-0.997;vs no DMARDs) and NSAIDs (0.77, 0.60-0.98;vs no NSAIDs). Conclusion: More severe COVID-19 outcomes in PsO, PsA and axSpA are largely driven by demographic factors (age, sex), comorbidities, and active disease. None of the DMARDs typically used in PsO, PsA and axSpA, were associated with severe COVID-19 outcomes, including IL-17i, IL-23/IL-12 + 23i, JAKi and apremilast.

Multisystem inflammatory syndrome in children related to COVID- 19 in Hospital Infantil de México Federico Gómez

Introduction: It was recently observed and described an association between a pediatric hyperinflammatory state and the infection by SARS-CoV-2 which was named Multisystem inflammatory syndrome in children related to COVID-19 (PIMS- TS) or Multisystem inflammatory syndrome (in children) MIS-C. Objectives: We aimed our study at describing the clinical features, epidemiologic characteristics, management, and prognosis. Methods: This is a retrospective, descriptive and observational study performed at the Hospital Infantil de Mexico Federico Gomez, a thirdlevel children's hospital in Mexico City. The study includes all the cases that met criteria for PIMS-TS/MIS-C of the RCPCH, WHO, and/or CDC, that were diagnosed and treated between March 2020 and March 2021. We identified a total of 41 cases. Results: The depicted table describe the demographics of our studied population. The highest incidence was seen in previously healthy, school-aged children. No differences were noted based on sex. In 50% of the cases, there was history of exposure to COVID-19. 7.3% of patients had an associated comorbidity. The SARS-CoV2 was isolated from CSF in one patient with PIMS. There were no documented cases of macrophage activation syndrome (MAS). While coagulopathy was observed, there were no cases of disseminated intravascular coagulation (DIC). These results are consistent with the results reported by Hoste L et al. Eur J Pediatr. 2021. Conclusion: The present study depicts the experience of our institution with the new nosological entity named PIMS. We highlight the null mortality, the effectiveness of steroids and gammaglobulin in lieu of biologic therapy as part of the management, and the predominance of previously healthy patients without significant comorbidities. We consider this a broad evaluation, as our sample size consisted of 41 patients from the same location.

Mortality of COVID-19 in patients with rheumatic diseases: Comparison to the general population in méxico

Background: COVID-19 outcomes in Mexican patients with rheumatic diseases (RDs) in comparison to general population patients are unknown. Objectives: To compare mortality and hospitalization of COVID-19 patients with RDs and those without. Methods: We included for this study all the Mexican patients with RDs and COVID-19 registered from April 17th to October 30th, 2020 in the COVID-19 Global Rheumatology Alliance registry. We compare clinical and demographic characteristics of patients with RDs and COVID-19 to patients with COVID-19 that were selected randomly from the Mexican Epidemiology database (1:3). A logistic regression analysis was performed to adjust for confusion variables. Results: We included 322 patients with COVID-19 and RDs and 969 controls without RDs. Table 1 shows the demographic characteristics and comorbidities of both groups. Bivariate analysis showed that patients with RDs had higher mortality, were older, and were more frequently hospitalized. Comorbidities, such as diabetes, hypertension, cardiovascular and renal diseases were also more frequent in patients with RDs. In the multivariate analysis, having a RD was no longer associated with mortality (Figure 1). Conclusion: Patients with RDs had higher comorbidities, hospitalizations, and mortality than the general population in the bivariate analysis. However, adjusted multivariate analysis showed that the odds for mortality were not increased because of having a RD. These findings suggest that the increased mortality of Mexican patients with RDs may be explained by the higher frequency of comorbidities in this population.

Factors associated with mortality in patients with rheumatic diseases and COVID-19 in Mexico

Background: As of the 25th of January 2021, more than 150 thousand deaths as consequence of COVID-19 have been reported in Mexico [1]. Advanced age, male gender and comorbidities have been described as risk factors for severe disease and mortality in general population [2]. COVID-19 mortality in Mexican patients with rheumatic and musculoskeletal diseases (RMDs) is unknown. Objectives: To describe characteristics of Mexican patients with RMDs and COVID-19, and to analyse factors associated with mortality. Methods: The Global Rheumatology Alliance COVID-19 (GRA) physician reported registry, is an international effort to collect information on COVID19 in adult patients with RMDs. GRA is an observational registry. The first patient from Mexico was registered on April 17, 2020. All Mexican patients registered in GRA until October 30, 2020 were included in this analysis. The association of mortality with demographic and clinical variables was estimated using logistic regression analysis. Results: A total of 323 patients were registered, with a median age of 52 (IQR 41-61) years old, 166 (51.4%) patients lived in Mexico City. The most frequent RMDs were rheumatoid arthritis, 149 (46.1%) and systemic lupus erythematosus, 24 (19.8%). Over a third of patients with RMDs and COVID-19 (119 (36.8%)) were hospitalized, and 43 (13.3%) died. Table 1 shows clinical and demographic characteristics. In the univariable analysis, the absence of comorbidities was a protective factor, OR 0.3 (95% CI 0.1-0.6). Factors associated with mortality at COVID-19 diagnosis were age over 65 years old, having type 2 diabetes, chronic renal insufficiency, treatment at COVID-19 diagnosis with corticosteroids or with CD20 inhibitors. In the multivariable adjusted analysis, these factors remained independently associated with mortality. No associations with other treatments or comorbidities at COVID-19 diagnosis were found. Conclusion: Mexican patients with RMDs and COVID-19 in the GRA physician reported registry had a mortality of 13.3%. Factors associated with mortality were those described in the general population, such as older age and being on corticosteroids and CD20 inhibitors treatment at COVID-19 diagnosis.