Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo-controlled study. METHODS: Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily. Glucocorticoid taper was recommended from weeks 0 to 12 and from weeks 24 to 36. The primary end point was the SLE Responder Index 4 (SRI-4) response at week 48. RESULTS: Patients (n = 260) were enrolled from 44 sites in 12 countries, with the majority from Latin America, the US, and Western Europe. The SRI-4 response rates at week 48 were 51% for fenebrutinib 150 mg once daily (P = 0.37 versus placebo), 52% for fenebrutinib 200 mg twice daily (P = 0.34 versus placebo), and 44% for placebo. British Isles Lupus Assessment Group-based Combined Lupus Assessment response rates at week 48 were 53% for fenebrutinib 150 mg once daily (P = 0.086 versus placebo), 42% for fenebrutinib 200 mg twice daily (P = 0.879 versus placebo), and 41% for placebo. Safety results were similar across all arms, although serious adverse events were more frequent with fenebrutinib 200 mg twice daily. By week 48, patients treated with fenebrutinib had reduced levels of a BTK-dependent plasmablast RNA signature, anti-double-stranded DNA autoantibodies, total IgG, and IgM, as well as increased complement C4 levels, all relative to placebo. CONCLUSION: While fenebrutinib had an acceptable safety profile, the primary end point, SRI-4 response, was not met despite evidence of strong pathway inhibition.

Characteristics associated with COVID-19 vaccine hesitancy: A nationwide survey of 1000 patients with immune-mediated inflammatory diseases.

OBJECTIVES: To identify potential predictors of COVID-19 vaccine hesitancy (C19-VH) in adults with immune-mediated inflammatory diseases (IMID). METHODS: A total of 1000 IMID patients were enrolled in this web-based cross-sectional study. A standardised and self-administered survey was designed by members of the Brazilian Society of Rheumatology Steering Committee for Infectious and Endemic diseases and distributed to IMID patients spread across Brazil. RESULTS: Of the 908 (90.8%) respondents eligible for analysis, 744 (81.9%) were willing to get vaccinated against COVID-19. In our multivariable logistic regression model, concurrent malignancy, fibromyalgia, hydroxychloroquine use, and recent corticosteroid pulse therapy were independently associated with higher odds of C19-VH. The short duration of COVID-19 vaccine clinical trials was the main reason for C19-VH. CONCLUSION: We identified novel characteristics potentially associated with C19-VH among adults with IMID. Greater awareness on the safety and efficacy of COVID-19 vaccines is needed for both IMID patients and attending physicians.

Temporomandibular joint involvement in rheumatoid arthritis patients: association between clinical and tomographic data.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and synovial hyperplasia, which usually affects multiple joints. The temporomandibular joint (TMJ) becomes susceptible to the development of changes resulting from RA. The aim of this study was to evaluate the presence of TMD and degenerative bone changes in TMJ in patients diagnosed with RA (rheumatoid arthritis). The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) questionnaire was used for clinical evaluation of the TMJ and for TMD classification of 49 patients of both sexes and all ages. Individuals who had already undergone prior treatment for TMD and/or with a history of craniofacial trauma were excluded. The participants underwent cone beam computed tomography (CBCT) exams to assess possible degenerative changes in the mandibular condyle and the articular eminence. The frequencies of the changes found are presented and the possible associations between clinical and CT findings analyzed using the chisquare test. It was found that 75% of the patients had complaints of pain in the orofacial region, including arthralgia, myalgia or both. As for the diagnoses, 100% of the sample was diagnosed as RDC/TMD Group III (arthralgia, osteoarthritis or osteoarthrosis). The presence of degenerative bone changes was found in 90% of the subjects, the most prevalent being flattening (78.7%) and osteophytes (39.3%). The association test suggested a greater tendency to develop degenerative changes in asymptomatic individuals (p = 0.01). The asymptomatic nature of the involvement of the TMJ in RA can hide structural damage seen in imaging. Thus, the importance of early diagnosis and treatment to reduce structural and functional damage is emphasized.

A artrite reumatoide (AR) é uma doença sistêmica, autoimune, caracterizada por inflamação crônica e hiperplasia sinovial, que usualmente afeta múltiplas articulações. Dentre estas, a articulação temporomandibular (ATM), tornase susceptível ao desenvolvimento de alterações. O estudo objetiva avaliar a presença de desordem temporomandibular (DTM) e altera ções ósseas degenerativas da ATM (articulação temporo man di bu lar) de pacientes diagnosticados com AR (artrite reumatóide). Como metodologia, aplicouse o questionário Research Diagnostic Criteria for Temporomandibular Disorder (RDC/ TDM) em para avaliação clínica da ATM e classificação da desordem temporomandibular em 49 pacientes de ambos os sexos e idade variável. Foram excluídos os indivíduos que já haviam realizado tratamento prévio para DTM e/ou com histórico de traumatismo crâniofacial. Posteriormente os participantes foram submetidos a exames de tomografia computadorizada de feixe cônico (TCFC) para avaliação de possíveis alterações degenerativas no côndilo mandibular e na eminência articular. Foram apresentadas as frequências das alterações encontradas e verificouse a associação entre os achados clínicotomográficos por meio do teste do Quiquadrado. Após a avaliação clínica verificouse que 75% dos pacientes possuíam queixas de dor na região orofacial, variando entre a presença de artralgia, mialgia ou ambas. Quanto aos diagnósticos, 100% da amostra apresentou diagnóstico do Grupo III do RDC/TMD (artralgia, osteoartrite ou osteoartrose). A presença de alterações ósseas degenera tivas foi encontrada em 90% dos indivíduos avaliados, sendo que as mais prevalentes foram aplainamento (78,7%) e osteófito (39,3%). O teste de associação sugeriu uma maior tendência de desenvolvimento de alterações degenerativas nos indivíduos assintomáticos (p = 0.01). O caráter assintomático do envolvimento da ATM na AR pode ocultar danos estruturais vistos em imagem. Assim, ressaltase a importância do diagnóstico e tratamento precoces para redução de danos estruturais e funcionais.