Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).

Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies.

OBJECTIVE: Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. METHODS: Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. RESULTS: The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. CONCLUSION: The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.

Systemic autoimmune myopathies: a prospective phase 4 controlled trial of an inactivated virus vaccine against SARS-CoV-2.

OBJECTIVES: To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. METHODS: This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. RESULTS: Patients and CTRL had comparable sex (P>0.99) and age (P=0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P<0.001), GMT [7.9 (95%CI 4.7-13.2) vs 24.7 (95%CI 30.0-30.5) UA/ml, P<0.001] and frequency of NAb (51.4% vs 77.2%, P<0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4-83.4) vs 63.0% (IQR 40.3-80.7), P=0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P=0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P>0.05). CONCLUSION: Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. TRIAL REGISTRATION: COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698.

Long-term effects of early pulse methylprednisolone and intravenous immunoglobulin in patients with dermatomyositis and polymyositis.

OBJECTIVE: To evaluate the long-term effects of pulse i.v. methylprednisolone (IVMP) or IVIG administered during the first year of diagnosis in DM and PM patients. METHODS: This is a retrospective single-centre cohort study of patients with PM/DM followed for up to 4 years from 2001 to 2017. We used Cox regression models to estimate hazard ratios (HRs) and assess the effects of early pulse IVMP or IVIG on three outcomes: complete clinical response, CS discontinuation, and survival. Analysis was adjusted for clinical, laboratory and treatment covariates. RESULTS: A total of 204 patients were included and categorized into four initial treatment groups: pulse IVMP (n = 46), pulse IVMP + IVIG (n = 55), IVIG (n = 10), and without IVMP or IVIG (n = 93). The groups of early pulse IVMP and pulse IVMP + IVIG had a higher HR for complete clinical response in the multivariate models (HR = 1.56, 95% CI: 1.05, 2.33, P = 0.029; and HR = 1.58, 95% CI: 1.02, 2.45, P = 0.041, respectively). Only the group of pulse IVMP + IVIG had a significant association with CS discontinuation in the multivariate analysis (HR = 1.65, 95% CI: 1.02, 2.68, P = 0.043). Early pulse IVMP or IVIG had no impact on mortality. CONCLUSION: Despite having a more severe disease profile, patients with PM/DM submitted to pulse IVMP or pulse IVMP + IVIG during the first year of diagnosis had a higher HR for complete clinical response, whereas the combination of pulse IVMP + IVIG had an association with CS discontinuation. Prospective long-term studies are warranted to confirm these benefits of early pulse IVMP and IVIG on patients with PM/DM.

Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies

Abstract Objective Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. Methods Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. Results The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. Conclusion The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.

Efficacy and safety of leflunomide as an adjuvant drug in refractory dermatomyositis with primarily cutaneous activity.

OBJECTIVES: To evaluate leflunomide as an adjuvant drug in refractory dermatomyositis (DM) with primarily cutaneous activity. METHODS: A retrospective, single-centre, cohort study including 18 adult patients with DM (classical or clinically amyopathic DM) and cutaneous activity from 2001 to 2016 was conducted. Patients were dependent on glucocorticoid and refractory to at least two full-dose immunosuppressants/immunomodulators or presented previous adverse events with immunobiological drugs. One immunosuppressant was maintained and leflunomide added to the treatment. Patients were followed for six consecutive months. RESULTS: Leflunomide proved effective and safe in 12 (66.6%) out of the 18 patients. There was total control of cutaneous activity and prednisone was tapered from 17.5 to 6.0 mg/day (p<0.001). In addition, two of these patients that also had muscle involvement improved muscle strength after leflunomide treatment. Side effects or inefficacy were observed in six patients. There were no cases of serious infection or death. CONCLUSIONS: Leflunomide therapy appears to be effective and safe as an adjuvant drug in refractory DM with primarily cutaneous activity. Further studies are needed to confirm this data.

Contraception for adolescents with chronic rheumatic diseases.

Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC.

Contraception for adolescents with chronic rheumatic diseases / Contracepção para adolescentes com doenças reumáticas crônicas

ABSTRACT Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC.

RESUMO A contracepção é uma questão importante e deve ser um motivo de preocupação em toda consulta médica de pacientes adolescentes e jovens com doenças reumáticas crônicas. Esta revisão narrativa discute métodos contraceptivos em adolescentes com lúpus eritematoso sistêmico (LES), síndrome antifosfolipídica (SAF), artrite idiopática juvenil (AIJ) e dermatomiosite juvenil (DMJ). Os métodos de barreira são seguros e todos os adolescentes com doenças reumáticas crônicas devem ser incentivados a usá-los. Os contraceptivos orais combinados (COC) são estritamente proibidos para pacientes com LESJ e SAF com anticorpos antifosfolípides positivos. A contracepção reversível de ação prolongada pode ser incentivada e oferecida rotineiramente a paciente adolescente com LES e outras doenças reumáticas. As pílulas que contêm somente progestina são seguras na maior parte das doenças reumáticas, embora a principal preocupação relacionada com seu uso por adolescentes seja a baixa adesão em decorrência da irregularidade menstrual. As injeções de acetato de medroxiprogesterona de depósito a cada três meses são uma estratégia altamente eficaz de contracepção, embora o seu uso em longo prazo esteja associado à diminuição na densidade mineral óssea. Contraceptivos orais combinados ou outros contraceptivos hormonais combinados podem ser opções para pacientes com AIJ e DMJ. O levonorgestrel oral deve ser considerado como um método de contracepção de emergência para todas as adolescentes com doenças reumáticas crônicas, incluindo pacientes com contraindicação para COC.

Reduction of ovarian reserve in adult patients with dermatomyositis.

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. METHODS: Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Müllerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. RESULTS: DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1±4.7 years, with disease duration of 5.6±3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of ≤1ng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. CONCLUSIONS: We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.

The high prevalence of metabolic syndrome in polymyositis.

OBJECTIVES: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that are associated with increased cardiovascular diseases (CVD). MetS has been systematically evaluated in all systemic autoimmune rheumatic diseases except for polymyositis (PM). This study aimed to evaluate the frequency of MetS in PM patients and analyse the possible association of MetS with traditional risk factors of CVD and PM-related clinical and laboratory features. METHODS: The present cross-sectional, single-centre study included 35 consecutive PM patients (Bohan and Peter, 1975) and 70 healthy controls. MetS diagnosis was determined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). RESULTS: The age, gender and ethnicity distributions between the PM and control groups were comparable (p>0.050). The median PM disease duration was 5 years. Compared with healthy subjects, PM patients had higher prevalence of MetS (45.7% vs. 20.0%, p=0.011). In an additional univariate analysis of PM patients with (n=26) and without (n=19) MetS revealed that patients with this complication were older (56.1±7.8 vs. 44.3±12.8 years; p=0.002) with more cumulative prednisolone doses, higher scores on the health assessment questionnaire and on the physician visual analogue scale (p<0.050). Disease duration was comparable between both groups (p>0.050). CONCLUSIONS: MetS and CVD risks are highly prevalent in PM. Monitoring for and early treatments of modifiable risk factors for CVD in PM patients are necessary.

[Inclusion body myositis: series of 30 cases from a Brazilian tertiary center]. / Miosite de corpos de inclusão: série de 30 casos de um centro terciário brasileiro.

OBJECTIVES: To describe a series of 30 consecutive patients with inclusion body myositis (IBM) from our tertiary center, from 1982 to 2012. MATERIALS AND METHODS: All patients fulfilled the criteria of Griggs et al. (1995) for IBM. RESULTS: The mean age of patients at disease onset was 60.8 � 11.9 years with disease duration of 8.0 � 5.2 years. Eighty % of patients were Caucasian, with similar distribution between genders. Weight loss in early disease was present in less than a quarter of cases. The main symptom was proximal weakness of the lower limbs followed by weakness of the upper (proximal and/or distal) limbs. One third of patients had dysphagia, whereas dysphonia was present in 16.7%, arthralgias in 6.7%, moderate dyspnea symptoms in 3.3% of cases. All patients received prednisone (1mg/kg/day). Several immunosuppressives were used as corticosteroid-sparing according to tolerance, side effects and/or refractoriness. Half of the patients still in follow-up remained stable according to clinical and laboratory data during the study. There were four cases of cancer, four cases associated with viral infections (HIV and hepatitis C virus) and three deaths (two because of sepsis secondary to community bronchopneumonia, and one because of congestive heart failure). CONCLUSIONS: This is the first Brazilian series of cases involving large sample of IBM. The profile of the patients analyzed in this study was comparable to those profiles described in literature, except that of IBM cases of our population are equally distributed in both genders and the interval between symptoms onset and diagnosis of the disease was relatively short. It is relevant to note the high frequency of neoplastic diseases and chronic viral infections in our population, reinforcing the need for specific epidemiological studies to verify these associations, once it is poorly described in the literature.

HELLP syndrome and its relationship with antiphospholipid syndrome and antiphospholipid antibodies.

OBJECTIVE: To perform a systematic review of the association between antiphospholipid antibodies, antiphospholipid syndrome (APS), and HELLP syndrome (Hemolysis; Elevated Liver enzymes; Low Platelet count), describing clinical features, outcome, pathophysiological findings, and treatment. METHODS: We performed a literature search in PubMed using the following MeSH entry terms: HELLP syndrome, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, and antiphospholipid syndrome. We limited our search to articles published in the English literature from 1994 to 2010. RESULTS: We identified 29 case reports/studies including a total of 51 pregnancies with HELLP syndrome in 50 patients. The majority of the cases occurred during the 28 to 36 weeks of pregnancy. Nausea, vomiting, epigastric, or right upper quadrant pain was the most frequently reported symptoms at disease onset. Elevated liver enzymes and low platelet count were reported in all studies. Concomitant hypertension and proteinuria were reported in 2/3 of the patients. Hepatic infarctions were observed in 33.3% pregnancies. However, thrombosis was also reported in the central nervous system, deep or superficial vein thrombosis, skin, intestine, bone, spleen, and adrenal glands. Treatment is still a matter of debate in HELLP syndrome. Aspirin, subcutaneous, intravenous, and oral anticoagulation, and prednisone have been used. In addition to the use of plasma exchange and fresh frozen plasma administration, intravenous immunoglobulins and plasmapheresis have been described. CONCLUSIONS: The incidence of obstetric events in patients with APS is a matter of great interest among rheumatology and gynecology and obstetrics professionals. The current knowledge that antiphospholipid antibodies/APS is not only a thrombotic disease, but also associated with microangiopathic features, can explain the greater prevalence of HELLP syndrome in these patients.