Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. METHODS: This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. RESULTS: Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. CONCLUSIONS: Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Transcranial Direct Current Stimulation Is Safe and Reduces Chronic Fatigue in Patients With Stable Systemic Lupus Erythematosus and Rheumatoid Arthritis.

To the best of our knowledge, this is the first case series to assess a combined technique of transcranial direct current stimulation (tDCS - a non-pharmacological and non-invasive brain stimulation) and aerobic exercise in one patient with systemic lupus erythematosus (SLE) and another with rheumatoid arthritis (RA) and significant chronic fatigue. We conducted five sessions of tDCS combined with low-intensity treadmill exercise. Fatigue levels were assessed using the Fatigue Severity Scale and the Visual Analog Scale for fatigue before (pre), immediately after five tDCS sessions (post-zero), and after six months (post-6-mo). The level of fatigue decreased, and functionality improved significantly post-zero and remained sustainable post-6-mo in both SLE and RA cases. There was only one mild and transient side effect (headache) specifically in the patient with RA, and no disease reactivation occurred in any of the cases. Our data showed that tDCS combined with aerobic exercise appears to be safe and promising for reducing fatigue and improving functionality in patients with SLE and RA. Randomized studies with larger sample sizes are required to corroborate our findings.

Transcranial direct current stimulation is safe and effective in autoimmune myopathies: a randomised, double-blind, sham-controlled trial.

OBJECTIVES: We aimed to assess the safety and efficacy of transcranial direct current stimulation (tDCS) in patients with systemic autoimmune myopathies (SAMs). METHODS: This prospective, randomised, sham-controlled, double-blind, study included 20 patients with SAMs allocated to receive sham or active tDCS (2mA, 20 minutes, 3 days). Electrodes were positioned with the anode over the C1 or C2, whereas the cathode was placed over the Fp2 or Fp1, respectively. The groups were evaluated in four periods with specific questionnaires and functional tests: pre-stimulation and after 30 minutes, three weeks, and eight weeks post-tDCS. RESULTS: Two patients from the sham group withdrew after the three sessions. The demographic data, type of myositis, disease duration, and disease status were comparable between the active and sham tDCS groups. After interventions, in the active tDCS group, the physical aspects of SF-36 in week eight, mean and better timed up-and-go test at each evaluation, peak torque of stimulated inferior limb extension improved significantly (p<0.05). The emotional aspect of SF-36 decreased only in the active tDCS group (p<0.001). The patients' adherence to the protocol was 100% and no serious adverse event was reported, including disease relapses. CONCLUSIONS: This study evidences the safety of tDCS, as well as its potential efficacy in improving muscle strength and function in SAMs patients. More studies with a larger sample and longer tDCS sessions are necessary to corroborate the results of the present study.

Work situation, work ability and expectation of returning to work in patients with systemic autoimmune myopathies.

OBJECTIVES: To document the work situation, the work ability and the expectation of returning to work among adult patients with systemic autoimmune myopathies (SAMs), and to identify the factors associated with each of these outcomes. METHODS: Cross-sectional study. The work situation (performing paid work vs out of work) was ascertained via a structured questionnaire. For those who were working, we applied the Work Ability Index (WAI; scale 7-49); and for those who were out of work, we applied the Return-to-Work Self-Efficacy questionnaire (RTW-SE; scale 11-66). RESULTS: Of the 75 patients with SAMs included, 33 (44%) were doing paid work and 42 (56%) were out of work. The work situation was independently associated with physical function, assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). A 1-point increase in the HAQ-DI (scale 0-3) decreased the chance of doing paid work by 66% (95% CI: 0.16, 0.74; P = 0.007). Patients performing paid work had a mean WAI of 33.5 (6.9). The following variables were associated with a decrease in the WAI score in the regression model: female sex (-5.04), diabetes (-5.94), fibromyalgia (-6.40), fatigue (-4.51) and severe anxiety (-4.59). Among those out of work, the mean RTW-SE was 42.8 (12.4). Cutaneous manifestations and >12 years of education were associated with an average increase of 10.57 and 10.9 points, respectively, in the RTW-SE. A 1-point increase in the HAQ-DI decreased the RTW-SE by 4.69 points. CONCLUSION: Our findings highlight the poor work participation in a well-characterized sample of working-age patients with SAMs. Strategies to improve work-related outcomes in these patients are urgently needed.

Factors associated with poor outcomes in SLE patients with COVID-19: Data from ReumaCoV-Brazil register.

OBJECTIVES: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study-"The ReumaCoV Brazil"-designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). RESULTS: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post-COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04-5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12-96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10-16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97-15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12-0.88], p = 0.02). CONCLUSION: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19.

High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome.

OBJECTIVES: Until now, researchers have not provided a well-defined muscle histological pattern for antisynthetase syndrome (ASSD). Therefore, we aimed to analyse the muscle biopsies of patients with anti-Jo-1 ASSD. METHODS: This study included 26 patients with anti-Jo-1 ASSD admitted for investigation of the disease and obligatorily with muscle impairment, from 2010 to 2021, whose serial frozen muscle sections were analysed. RESULTS: Patients' mean age at disease diagnosis was 42.8±11.6 years, and the female gender was most predominant. Concerning muscle biopsies, cell infiltrates were present in 76.9% of the samples, and they were mainly located at the endomysium area (70%), with a predominance of macrophages (92.9%). Fiber muscle necrosis was present in 92.3% and was diffused in 54.2%. Expression of MHC-I was seen in all samples. Samples were mostly marked by the presence of CD68+ and discreet/low CD4+ and CD8+ staining, which is consistent with a higher predominance of observed necrosis and macrophage cell infiltrates. In general, 38.5% of patients had a necrotising myopathy pattern in muscle biopsies, whereas 34.6% and 26.9% had a general inflammatory myopathy pattern and nonspecific myopathy, respectively. This necrotising myopathy pattern was not associated with the demographic, clinical, or laboratory data. CONCLUSIONS: Our data show that almost 40% of patients with well-defined anti-Jo-1 ASSD with objective muscle impairment have a necrotising myopathy pattern in their muscle biopsies. Although this pattern is more classically related to immune-mediated necrotising myopathies, in association with clinical manifestations and the presence of anti-Jo-1 autoantibodies, this characteristic may lead to ASSD diagnosis.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose.

OBJECTIVE: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. METHODS: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). RESULTS: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. CONCLUSION: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

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).

Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine.

OBJECTIVES: To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). METHODS: A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies-NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. RESULTS: Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P < 0.001), NAb positivity (5.5 vs 83.5%, P < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P = 0.001). Negative NAb was associated with older age (P = 0.015), RA (P = 0.002), SSc (P = 0.026), LEF (P = 0.016) and rituximab use (P = 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; P = 0.047), LEF (OR = 0.32, P = 0.036) and rituximab use (OR = 0.19, P = 0.022) were independently associated with negative NAb after the fourth vaccine dose. CONCLUSIONS: This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, CoronavRheum #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.

Effect of an exercise bout before the booster dose of an inactivated SARS-CoV-2 vaccine on immunogenicity in immunocompromised patients.

This randomized controlled study aimed to investigate whether a single bout of exercise before the homologous booster dose of a SARS-CoV-2 inactivated vaccine could enhance immunogenicity in patients with spondyloarthritis. We selected 60 consecutive patients with spondyloarthritis (SpA). Patients assigned to the intervention group performed an exercise bout comprising three exercises. Then, they remained at rest for 1 h before vaccination. The control group remained at rest before vaccination. Immunogenicity was assessed before (Pre) and 1 mo after (Post) the booster using seropositivity rates of total anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG (GMT), frequency of neutralizing antibodies (NAb) positivity, and NAb activity. At Pre, 16 patients from the exercise group and 16 patients from the control group exhibited seropositivity for IgG (59% vs. 57.1%), and 1 mo after the booster dose, seropositivity occurred in 96% versus 100% of the cases. Only 10 patients from the exercise group and 12 patients from the control group showed positive NAb serology at Pre (37% vs. 42.8%). One month following the booster, NAb positivity was 96% versus 93%. GMT was comparable between groups at Pre. At Post, GMT increased similarly in both groups. Likewise, NAb activity was similar between groups at Pre and increased similarly in both of them as a result of the booster (47.5% vs. 39.9%). In conclusion, a single bout of exercise did not enhance immunogenicity to a homologous booster dose of an inactivated SARS-CoV-2 vaccine among patients with spondyloarthritis.NEW & NOTEWORTHY We tested the role of exercise as an adjuvant to a booster of a COVID-19 vaccine. Immunocompromised patients were immunized after an acute bout of exercise or not. Patients exhibited an excellent immunogenicity in response to the booster dose. Exercise did not add to the vaccine effects on IgG or neutralizing antibodies.

Analysis of patient-physician discrepancy in global assessment of systemic autoimmune myopathy disease activity.

OBJECTIVES: To compare the perception of disease activity (DA) between adult patients with systemic autoimmune myopathies (SAMs) and their physicians, and analyse possible sources of discordance. METHODS: This cross-sectional study included 75 patients with SAMs. Patients and physicians rated the global DA on a 0-10 cm visual analogue scale. A discrepancy score was calculated by subtracting physician assessment from patient assessment. Three groups were defined: (I) no discrepancy: difference within -2.0 to +2.0; (II) negative discrepancy (ND): difference <-2.0 (patient underrated DA in relation to physcian); (III) positive discrepancy (PD): difference >+2.0 (patient overrated DA in relation to physician). Logistic regression was used to identify predictors of discordance. RESULTS: Discordance in patient-physician assessment of DA was found in 21 (28%) cases. ND was observed in 3 (4%), PD in 18 (24%), and no discrepancy in 54 (72%) assessments. Due to the small number, ND cases were excluded from the analysis. PD was associated with older age, personal history of depression, past joint involvement, higher MMT-8 and lower extramuscular DA. In the regression model, for each additional year of age, the chance of PD increases, on average, by 9% (OR 1.09; 95%CI 1.01-1.17, p=0.034). Personal history of depression increases the chance of PD by 829% (OR 9.29; 95%CI 1.52-56.89, p=0.016). CONCLUSIONS: Almost 30% of patients had discordance in DA assessment from their physicians. The majority of them overrated their DA. These patients tend to be older and are more likely to have personal history of depression, past joint involvement, and milder disease.

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis.

INTRODUCTION: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). METHODS: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. RESULTS: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. CONCLUSIONS: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide.

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.

Serum Myostatin and Follistatin Levels in Patients With Dermatomyositis and Polymyositis.

BACKGROUND: Myostatin is a protein in the TGF-ß family that negatively regulates muscle mass, and follistatin is a myostatin antagonist. OBJECTIVE: The aim of this study was to measure serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients and correlate these levels with muscle strength, fatigue, functional capacity, damage, and serum levels of muscle enzymes. METHODS: This was a multicenter cross-sectional study including 50 patients (34 dermatomyositis and 16 polymyositis [PM]) and 52 healthy individuals (control group [CG]). The disease status was evaluated according to the International Myositis Assessment & Clinical Studies. Fatigue was rated according to the Fatigue Severity Scale, and body composition was measured using dual-energy x-ray emission densitometry. Myostatin and follistatin were measured using enzyme-linked immunosorbent assays. RESULTS: Mean age was 50.9 ± 14.0 years, and mean disease duration was 89.2 ± 80.9 months. There were no differences in levels of myostatin (14.15 ± 9.65 vs. 10.97 ± 6.77 ng/mL; p = 0.131) or follistatin (0.53 ± 0.71 vs. 0.49 ± 0.60 ng/mL; p = 0.968) between patients and the CG. However, myostatin levels were higher in PM than CG (16.9 ± 12.1 vs. 11.0 ± 6.8 ng/mL; p = 0.036). There was no difference in serum myostatin among patients with and without low lean mass. Patients not treated with corticosteroids had higher serum levels of myostatin than the CG. There was a weak negative correlation between follistatin and Manual Muscle Testing and a Subset of Eight Muscles and a weak positive correlation between follistatin and Healthy Assessment Questionnaire. CONCLUSIONS: Serum levels of myostatin and follistatin did not differ between dermatomyositis and PM patients and control subjects. The assessment of serum levels of myostatin and follistatin in idiopathic inflammatory myopathy patients seems not to be helpful in clinical practice.

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.

Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study.

BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.