TREATMENT WITH TOFACITINIB ATTENUATES MUSCLE LOSS THROUGH MYOGENIN ACTIVATION IN COLLAGEN-INDUCED ARTHRITIS
Rafaela Espírito Santo, Thales Rosa, Bárbara Bartikoski, Mirian Farinon, Jordana Silva, Renata Pedó, Ricardo Xavier, Luis Dulcey, Raimondo Caltagirone, Juan Sebastian, Theran Leon, Felix Rangel, Rafael Guillermo, Parales Strauch, Valentina Cabrera Peña, Maria Paula Ciliberti, Edgar Camilo Blanco, Nancy Paola Duarte-Delgado, Angie Katherine Segura, Catherin Tovar- Sánchez, Sandra Pulido, Juan Manuel Bello, Daniel G Fernández-Ávila, Sandra Amado, Consuelo Romero-Sánchez, Luz-Stella Rodríguez, Jonathan Carvajal-Veloza, Jaime-Andrés Rubio-Rubio, Gustavo Salguero, Luz Dary Gutiérrez-Castañeda, Gabriel Santiago Rodríguez-Vargas, Pedro Santos-Moreno, Dario Echeverri, Paula-Katherine Bautista-Niño, Luis David Sáenz, Adriana Rojas-Villarraga, Sciences Basic, Group, Natalia De Avila Gonzalez, Dionicio A Galarza-Delgado, Iris J Colunga- Pedraza, Jose R Azpiri-Lopez, Angel G Arias-Peralta, Victor M Beltrán- Aguilar, Valeria Gonzalez-Gonzalez, Jesús A Cardenas-De La Garza, Carlos Eduardo Garcez Texeira, Marilia Paula, Souza Dossantos, Lilian Tereza Lavras Costallat, Simone Appenzeller, Sofia Rostan, Sandra Consani, Carolina Diaz, Lucia Fernandez, Emilia Moreira, Laura Yametti, Clinica Medica, Clínica Quirúrgica, Carolina Ayelen Isnardi, Margarita Landi, Leonel Cruces, Pablo Maid, Maressa Lirio, Ketty Machado, Raquel Lima, Cristiane Kayser, Edgard Neto, Sandra Ribeiro, Érica Serrano, Samira Myiamoto, Valéria Valim, Programa De Pós Graduação, Saúde Coletiva Da Ufes, Adriana Maria Kakehasi, Claudia Marques, Ana Gomides, Edgard Torres Neto, Gecilmara Salviato Pileggi, Licia Mota, Odirlei Monticielo, Marcelo Pinheiro, Gilda Aparecida Ferreira, Priscila Dias, Cardoso Ribeiro, Flavia Maria Matos, Melo Campos Peixoto, Erika Biegelmeyer, Ketty Lysie, Libardi Lira Machado, Sandra Lúcia, Euzébio Ribeiro, Natália Sarzi Sartori, Vitor Alves Cruz, Vanessa De Oliveira Magalhães, Mariana Freitas De Aguiar, Alexandre Wagner, Silva De Souza, Charlles Heldan De Moura Castro, Marcelo De Medeiros Pinheiro, Odirlei André Monticielo, Viviane Angelina De Souza, Andréa Teixeira-Carvalho, Ricardo Machado Xavier, Ana Karla, Guedes De Melo, Valderilio Feijó Azevedo, Rejane Maria Rodrigues De Abreu Vieira, Edgard Torres, Reis Neto, Valeria Valim, Emilia Inoue Sato, Safer Study, UNIFESP São Rheumatology, Paulo, Vitor Cruz, Lira Machado, Vanezia Gonçalves Da Silva, Karina Rosemarie, Lallemand Tapia, ; Lunara, Baptista Ferreira, Ana Paula, Neves Burian, ; Laiza, Hombre Dias, Carolina Strauss Estevez Gadelha, Yasmin Gurtler, Pinheiro De Oliveira, Marina Deorce De Lima, ; Laís, Pizzol Pasti, Juliana Ribeiro De Oliveira, Laissa Fiorotti, Mariana De Oliveira Macabú, Pietra Zava Lorencini, ; Flávia, Maria Matos, ; Charlles, Heldan De, Moura Castro, ; Sandra, Lúcia Euzébio, ; Rosely, Holanda Da, Silva Sanches, Antonio Luiz Boechat, Vitória Miki, Pang Takatani, Clarissa Ruas, ; Davi, Queiroz Rego, Roberta Beatriz, Naz- Areth Alagia, ; Russian, Teixeira Rebello, Juliana Bühring, ; Natália, Sarzi Sartori, Nicole Pamplona Bueno De Andrade, Maria Luísa Gasparini, ; Tâmara, Santos Melo, Jozelia Rêgo, ; Rejane, Maria Rodrigues, Abreu Vieira, Adah Sophia, Rodrigues Vieira, ; Anna, Carolina Faria, Moreira Gomes Tavares, Aline Teixeira De Landa, Teixeira De Landa, Maria Cecília, Dias Corrêa, ; Valderilio, Feijó Azevedo, ; Olindo, Assis Martins-Filho, Vanessa Peruhype-Magalhães, ; Odirlei, André Monticielo, ; Edgard Torres, ; Gilda, Aparecida Ferreira, ; Viviane, Angelina De Souza, Ricardo Machado, Emilia Inoue Sato, Valeria Valim, ; Gecilmara, Salviato Pileggi, ; Nilzio, Antionio Da Silva, Florencia Valdez Donelli, Virginia Carrizo Abarza, Carolina A Isnardi, Andrea B Gomez Vara, Emilse E Schneeberger, Gustavo Citera, Gimena Gomez, Rosana Quintana, Karen Roberts, Guillermo J Pons-Estel, Sar-Covid Registry, Instituto Rheumatology, Rehabilitación De, Psicofísica, Paula María Corbalán, Mariana Pera, Gabriela Vanesa Espasa, María Lilia Leguizamón, Ana Lucía Barbaglia, María Constanza Bertolaccini, Luciana González Lucero, Hector Raul Sueldo, Rosana Nieves Chehin, Rodrigo Hernán Tomas-Grau, Diego Ploper, Esteban Vera Pinguitore, Benjamín Socías, César Luis Ávila, Silvia Inés Cazorla, Carolina Maldonado Galdeano, Veronica Inés Bellomio, C Padilla, Maria Da, Penha Gomes Gouveia, Laiza Hombre Dias, Débora Marques Veghini, Flávia Maria Matos, Camila Maria Paiva, França Telles, Samuel Elias, Basualto Dias, Evelyn Thaís, Karnopp, Rodrigo Poubel Vieira De Rezende, Katia Lino Baptista, Emilia Inoue Sato, Valeria Valim, Lucilatome Garcia, Cecilia Tizatto Barrros, Giovanna Dib, Da Almeida, Gabriela Bacellar Marques, Samuel Basualto Dias, Sebastiao Barreto, Falcao Neto
Objectives: The loss of muscle mass observed in Rheumatoid Arthritis (RA) patients occurs either by activation of catabolic pathways or by inhibition of anabolic pathways. Despite having a list of drugs capable of treating RA inflammation, the effect of these therapeutic interventions on muscle have not been elucidated. Our objective was to evaluate the effect of tofacitinib on muscle mass of collagen-induced arthritis (CIA) in mice. Methods CIA was induced in male DBA/1 J mice. Animals were randomized into 3 groups: CIA + tofacitinib (CIA-TOF; n = 10); CIA + vehicle (CIA-VEH; n = 10); healthy controls (CO; n = 9). Vehicle (PBS) or tofacitinib 15 mg/kg were administered twice a day, between days 18 and 45 after the disease induction. Clinical score, edema and body weight were evaluated during the experimental period. Tibio-tarsal joints were collected for assessment of disease histopathological score, and tibialis anterior (TA) and gastrocnemius (GA) muscles were weighed to assess muscle mass. Muscle atrophy was evaluated by measurement of TA myofiber cross-sectional area (CSA). Expression of proteins related to muscle regeneration or catabolism (Pax7, MyoD, myogenin and Murf-1) were evaluated by Western blot in GA homogenates. Serum inflammatory markers (TNF and IL-6) were evaluated by ELISA. Results Tofacitinib treatment decreased arthritis severity by reducing clinical score (p = 0.03) and hind paw edema (p = 0.04) than CIA-VEH group. CIA-TOF showed weight gain (p = 0.02), higher TA (p = 0.009) and GA (p = 0.02) weights, and increased CSA compared to CIA-VEH group (p = 0.01). On day 45, CIA-TOF presented increased muscle strength compared to CIA-VEH group (p = 0.006), however, no difference was found in the fatigue parameter among groups (p > 0.05). The expression of Pax7 was unchanged (p = 0.07), while MyoD expression showed an increase trend, and myogenin expression was significantly increased in CIA-TOF compared to CIA-VEH (p = 0.04) and CO groups (p = 0.02). The treatment did not significantly modify Murf-1 expression. Compared to CIA-VEH group, CIA-TOF mice showed decreased serum levels of TNF (p = 0.04), and no difference in IL-6 serum levels (p = 0.08).
Conclusion Tofacitinib attenuated muscle loss in arthritic mice, as increased muscle weight and muscle CSA were detected in treated mice. Additionally, an increased activation of satellite cells regeneration, based on the expression of myogenin, is a potential mechanism involved in tofacitinib-protection against muscle loss.
Dasa Complexo Hospitalar de Niterói, Niterói, Rio de Janeiro, 16 Pediatrics, Conclusion: LV systolic and diastolic function changes in the rheumatic disease population, especially RA, SLE, and PsA, are higher in comparison with healthy people and affect the prognosis in these patients; these changes can be detected by echocardiogram, which is a feasible and safe tool that may prevent complications and improve the prognosis with early detection and management of these patients' cardiac involvement. Disclosure Objectives: NLR and PLR are easily measured, reproducible, and inexpensive markers of inflammation that could guide our therapeutic decisions in patients with Rheumatoid Arthritis (RA) in absence of less accessible tests such as CRP or ESR. The objective of the study was to assess the correlation of NLR and PLR with disease activity.
Methods: The study included 190 patients with a diagnosis of RA in accordance with the the 2010 ACR/EULAR classification criteria. Patients with systemic diseases, such as diabetes mellitus, hypertension, chronic renal failure, coronary artery disease, chronic obstructive pulmonary disease, cancer, hematologic disease, acute or chronic infection, pregnancy or in the post-partum period or with a granulomatous chronic disease were excluded. All patients underwent a workup including detailed clinical history and physical examination. The activity of RA was determined with the DAS28 CRP score. All analysis were performed using a p < 0.05 as..
References
Abbvie, Aurinia, Myers Squibb, Lilly, Company et al., Board of UK National Ankylosing Spondylitis Society, and has been: a Chair of the British Society for Spondyloarthritis, C. de Lima Tostes Employee with: C. De Lima Tostes is an employee and shareholder of: Eli Lilly and Company Keywords: Axial Spondyloarthritis, Ixekizumab, Psoriasis PANLAR2023-1300 HLA-B27 POSITIVITY IN A LARGE MISCEGENATED POPULATION OF 5,389,143 HEALTHY BLOOD MARROW DONORS IN BRAZIL Gustavo Resende* 1 , Percival Sampaio-Barros 2 , Carla Saad 2 , Danielli Oliveira 3 , Julio Silvio Bueno Filho 4 , and Marcelo Pinheiro 5 . 1 Serviço de Reumatologia, Hospital das Clínicas da UFMG, Belo Horizonte, 2 Disciplina de Reumatologia, Universidade de São Paulo (USP), São Paulo, 3 REDOME, Instituto Nacional de Câncer (INCA), Rio de Janeiro, 4 Departamento de Estatística,
doi:10.1007/s40122-021-00310-8ReferenceCarlin, Feldman, Krueger, Menter, Krueger, Conclusion: In this cohort, patients who had failed to TNF-i had numerically lower retention and persistence of treatment with GLM. Globally, having previously received b/ts-DMARDs and not having health insurance was associated with lower retention, Reference
Hoogen, Verhoef, & Den, Broeder, Disclosure of Interest: None declared Keywords: Biological Therapies, Psoriasic Arthritis, Spondyloarthritis SPONDYLOARTHROPATIES AND OTHER INFLAMMATORY ARTHROPATIES PANLAR2023-1391 RETENTION RATE, PERSISTENCE AND EFFICACY OF GOLIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS AND AXIAL SPONDYLOARTHRITIS WITH PREVIOUS FAILURE TO OTHER TNFΑ INHIBITORS Carolina Ayelen Isnardi* 1 , Emma Estela Civit De Garignani 2 , Ingrid Strusberg 3 , Eduardo Albiero 4 , Rodrigo Garcia Salinas 5 , Edson Velozo 6 , Enrique Soriano 7 , Sergio Paira 8 , María Julieta Gamba 9 , and Gustavo Citera 1 . 1 Rheumatology, Instituto de Rehabilitación Psicofísica, CABA, 2 Rheumatology, Hospital El Carmen, Mendoza, 3 Rheumatology, Instituto Médico Strusberg, Córdoba, 4 Rheumatology, Sanatorio Allende, Cordoba, 5 Rheumatology, Hospital Italiano de La Plata,
doi:10.1093/rheumatology/keab741Lilly, Company, Paulo, Brazil, Methods: An integrated safety analysis consisting of data from 25 randomised clinical trials (RCTs; 17 PsO, 4 PsA, 4 axSpA) was used to examine long-term safety of IXE. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for all pooled studies by years of therapy and overall through March 2022, and reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at successive year intervals. Additional safety outcomes included selected safety topics of interest (among others). Results: A total of 6892 patients with PsO, 1401 patients with PsA, and 932 patients with axSpA, with a cumulative IXE exposure of 18025.7 PY for PsO, 2247.7 PY for PsA, and 2097.7 PY for axSpA were included in this analysis. The IRs per 100 PY for any TEAE were as follows
Llc, House, States, Janssen Latin America, Columbia et al., Disclosure of Interest: None declared Keywords: connective tissue disease, interstitial lung disease, multidisciplinary team PANLAR2023-1396 AUTOIMMUNE THYROIDITIS IN THE RHEUMATOLOGY CLINIC: FINDINGS IN A COHORT OF PATIENTS FROM SOUTHWESTERN COLOMBIA Juan Sebastian Segura-Charry* 1 , Maria Alexandra Parada-Martinez 1 , Adriana Rojas-Villarraga 2 , Jairo Cajamarca-Baron 3 , and Enrique Calvo-Paramo 4
Ospina-Pérez* 1, Valencia-Patiño 1, Díaz-Coronado, Objectives: To evaluate the association between the doses of prednisone (PDN) and left ventricle (LV) geometry in RA patients. Methods: Observational, cross-sectional study. Patients aged 40 to 75 who met the 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis were included. Patients with a history of cardiovascular disease were excluded. Patients were divided into 2 groups if receiving ≤5 or > 5 mg of PDN daily. Transthoracic echocardiography was performed by one certified echocardiographer blinded to clinical information. LV geometry was assessed by relative wall thickness (RWT) and indexed LV mass. The distribution between groups was evaluated with the Kolmogorov-Smirnov test. The correlation between the use of low doses of prednisone and left ventricle geometry parameters was assessed by Spearman's correlation coefficient. A value of p ≤ 0.05 was considered statistically significant. Results: A total of 63 patients were included. The mean age of RA patients was 54.8 ± 9.0, mostly women (96.8%), with a prevalence of dyslipidemia (30.2%) and obesity (30.2%). There was no correlation between the dose of PDN (high or low) and LV geometry (Figure 1). Conclusion: There was no difference between the use of low-dose and high-doses of PDN
Psa, None
Raúl, Larcade, Miguel ; Chimenti, Fonti, Conigliaro et al., Objectives: Pharmacovigilance is the science responsible for the detection and monitoring of possible drug adverse events (DAE) in the administration of medications. In pharmaceutical service process, the information generated through its programs constitutes evidence that provides a solution to the management of drug-related problems, especially those obtained by biotechnology. The aim of this study was to show the main DAEs and drug adverse reactions (DARs) with the use of anti-TNF (Anti-Tumor Necrosis Factor) drugs detected by the Pharmacovigilance program of an IPS specialized in rheumatology during the period 2018-2022. Methods: The current method carried out in the institution is the so-called Spontaneous Notification. A historical review of the DAE and DAR detected by an institutional Pharmacovigilance program with the use of Anti-TNF drugs, in patients with autoimmune diseases, during the period 2018-2022, was carried out. Indicators were established through descriptive statistics to measure the frequency of DAE and DAR. Results: 408,914 medical records were reviewed, the Table shows the comparative percentages of DAE and DAR detected by the program between conventional disease-modifying antirheumatic drugs (csDMARDs) and biologics during the follow-up period. The Pharmacovigilance program had growth in the detection of DARs with the use of anti-TNF drugs, strengthening knowledge in the information for these. The causality with the anti-TNF was established, being the DAE classified as probable and the DAR as possible. Of the total subgroup of patients treated at the institution for medication application,
doi:10.1097/MD.0000000000013955Torres ; Agudos Dr, Tornú, Flores * 1, Tornú, Manuel, Bande 1 on behalf of Hospital General de Agudos Dr. E. Tornú, Maria Alejandra Medina 1 on behalf of Hospital General de Agudos Dr. E. Tornú, Diana Klajn 1 on behalf of Hospital General de Agudos Dr. E. Tornú, José ÁAngel Caracciolo 1 , Mariana Pera 2 , Paula Corbalán 2, Julia Sosa 4 on behalf of Hospital General de Agudos Dr. E. Tornú, Maria Paula Kohan 5 on behalf of Hospital General de Agudos Dr. E. Tornú, Alejandro Muñoz 6 on behalf of Hospital General de Agudos Dr. E. Tornú, Maria Correa
