RMD Open

ObjectivesOptimization of biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) may be feasible in those who have maintained remission for at least six months. However, this approach carries the risk of disease flare, underscoring the need for reliable predictors to guide clinical decisions. MethodsThe OPTIBIO trial (EudraCT 2012-004482-40) was a phase IV, randomized, open-label, non-inferiority study conducted in five hospitals in Spain. RA patients in sustained remission on stable bDMARD therapy were randomized 1:1 to standard care or dose reduction. The primary outcome was to compare to proportion of joint flare at 12 months by a non-inferiority analysis analyzed by the intention-to-treat principle and identify predictors for flare and sustained remission. Results195 patients were randomized: 99 to the control group and 96 to the optimization group. Thirty-nine flares occurred (optimization: 22.7%, control: 17.2%), with a risk difference of -5.5% (95% CI: -16.8% to 5.7%; P = 0.33). Two predictive models were developed: one for flares (AUC: 0.84) including 3v-DAS28-CRP, VAS pain, erosions, systolic blood pressure, and hemoglobin, and another for sustained remission (AUC: 0.77) including 3v-DAS28-CRP, age, and rheumatoid factor. Adding molecular biomarkers improved AUCs to 0.91 and 0.88, respectively. No significant differences in adverse events were observed. ConclusionbDMARD dose optimization was non-inferior to standard therapy on the flare rate but demonstrated similar safety. Predictive models for remission and flares were developed, which may help select patients to ensure safe implementation of this strategy, highlighting the need for personalized treatment. Key messagesO_LIbDMARD dose optimization was non-inferior to standard therapy on the flare C_LIO_LIClinical models classified patients in terms of disease severity C_LIO_LIIncorporation of molecular markers to clinical models improved their prediction power C_LI

OBJECTIVESTo investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19. METHODSA cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms. RESULTS959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. All patients had a successful recovery and only one patient required admission in the intensive care unit. When using the same classification criteria (only COVID-19 positive cases with pneumonia), COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 8.65%)] and [0.58% (95% CI 5.62 to 5.99%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002). CONCLUSIONAdult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population. Our exploratory analysis suggests that the proportion of COVID-19 suspected cases differs between tDMARDs.

BackgroundIn this pandemic, it is essential for rheumatologist and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRD). We want to assess the role of targeted synthetic or biologic disease modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. MethodsAn observational longitudinal study was conducted (1stMar to 15thApr 2020). All patients from the rheumatology outpatient clinic from a hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, NSAIDs and conventional synthetic DMARDs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19, was expressed per 1,000 patients-month. Cox multivariate regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR. Results3,591 IRD patients were included (5,896 patients-month). Concerning csDMARDs, methotrexate was the most used followed by antimalarial. 802 patients were on ts/bDMARDs, mainly anti-TNF agents, and rituximab. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 [95%CI: 7-11.9]. In the multivariate analysis, older, male gender, presence of comorbidities and specific systemic autoimmune conditions (Sjoegren, polychondritis, Raynaud and mixed connective tissue disease) had more risk of hospital admissions regardless other factors. Exposition to ts/bDMARDs did not achieve statistical signification. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. ConclusionThis study provides additional evidence in IRD patients regarding susceptibility to moderate-severe infection related to COVID-19.

ObjectivesDue to their underlying disease as well as therapeutic immunosuppression, children and adolescents with rheumatic and musculoskeletal diseases (RMD) may be at higher risk for a severe course or worse outcome of COVID-19, and SARS-CoV2 infection may trigger a flare of the RMD. To address these issues, a specific SARS-CoV-2 questionnaire was implemented in the National Pediatric Rheumatology Database (NPRD) in Germany. MethodsDemographic, clinical and treatment data from juvenile patients with RMD as well as data about SARS-CoV-2 infection like test date and method, clinical characteristics, disease course, outcome and impact on the disease activity of the RMD documented on this questionnaire were analyzed. ResultsFrom April 17th, 2020, to February 14th, 2021, data were collected from 79 patients (53% female) with RMD with median age of 14 years, diagnosed with juvenile idiopathic arthritis (57%), autoinflammatory (23%) and connective tissue disease (8%). Sixty-one patients (77%) received disease-modifying antirheumatic drugs (DMARDs), 43% biologic DMARDs, and 9% systemic glucocorticoids. Sixty patients (76%) developed symptoms of COVID-19. Disease severity was mild and outcome was good in the majority of patients. Two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure. In 84% of SARS-CoV-2-positive patients, no relevant increase in disease activity of the RMD was observed. ConclusionsIn our cohort, COVID-19 in juvenile patients with RMD under various medications was mild with good outcome in the majority of cases. SARS-CoV-2 infection does not appear to have a relevant impact on disease activity of the underlying condition.

This study assessed the evidence on the efficacy of tapering anti-TNF, JAK inhibitors, and tocilizumab in rheumatoid arthritis patients. In February 2024, a systematic review was conducted by searching Medline, Embase, Web of Sciences, and the Cochrane Library for randomized controlled trials comparing the efficacy of tapering vs standard treatment. The outcomes evaluated were the maintenance of low disease activity (LDA), remission, and flare-ups. A meta-analysis was conducted when data were available. The risk of bias was assessed using RoB 2. The study was registered on PROSPERO. A total of 2861 records were identified, with 1638 records screened after removing duplicates. Finally, fifteen studies involving 2782 patients were included. Follow-up ranged from 6 months to 3.5 years. Tapering anti-TNF did not affect LDA maintenance while showing a lower probability of maintaining remission (RR 0.69, 95% CI 0.57-0.84) and a higher risk of flare-ups (RR 1.96, 95% CI 1.57-2.45). Tapering JAK inhibitors showed a decreased probability of maintaining LDA (RR 0.83, 95% CI 0.76-0.91) and remission (RR 0.86, 95% CI 0.75-0.99), and more frequent and earlier flares. Tapering tocilizumab also resulted in a lower probability of maintaining LDA or remission and a higher risk of flares. Although tapering anti-TNF did not affect LDA maintenance, due to the increased risk of flare-ups and reduced remission probability, routine dose tapering of anti-TNF, JAK inhibitors, and tocilizumab for all patients is not recommended. Identifying patients who may benefit from tapering is crucial.

BackgroundThe recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressive patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biologic agents may suppose a risk or protection against SARS-CoV2 infection however, it has been suggested that severe respiratory forms of COVID-19 occur as result of exacerbated inflammation status and cytokine production. This prompted the use of IL-6 (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV2. ObjectivesTo estimate COVID-19 infection rate in patients treated with biologic agents for rheumatic inflammatory diseases, determine the influence of biologic agents treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in Leon, Spain. MethodsWe performed a retrospective observational study including patients seen at Rheumatology department who received biological therapy for rheumatic diseases between December 1st 2019 and June 1st 2020 and analysed COVID-19 infection rate. All patients being attended at the rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biologic agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biologic agent and need for hospitalization. We performed a multivariate logistic regression model to assess risk factors of hospital admission. ResultsThere was a total of 3711 patients with COVID-19 requiring hospitalization. 30 patients out of a total of 820 patients (3.6%) receiving biological therapy had contracted COVID-19 and four required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. A total of 423 patients died, 2 of which received treatment with biologic agents. Patients who tested positive for COVID-19 were older (female: median age 61.8 IQR 46.5-75; male: median age 68 IQR 48.5-72) than those who were negative for COVID-19 (female: median age 58.4 IQR 48-69; male: median age 55.9 IQR 46-66) and more likely to have cardiovascular disease (27 % vs 10%, OR 3. 41 (CI 1.47 - 7.94), p 0.004), be active smokers (13% vs 5%, OR 3.14 (CI 1.04-9.47), p 0.04) and receiving treatment with IL-12/23 inhibitors (6.7% vs 1.4%, OR 5.06 (CI 1.07-23.91) and rituximab (13% vs 2%, 2.66 (CI 1.03-7.27), p 0.04) and were less likely to be receiving treatment with IL-6 inhibitors (0% vs 14%, CI (0.006-0.97, p <0.05). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bsDMARD proportions. IL-1 inhibitors, IL6 inhibitors, JAK inhibitors and belimumab treated patients showed the lowest incidence of COVID-19 among adult rheumatic patients. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative were found. ConclusionsOur findings suggest that use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.

BackgroundThe susceptibility of patients with rheumatic diseases, and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. MethodsWe performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with SARS-CoV-2 positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. ResultsPatients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Systemic autoimmune or immune mediated diseases (AI/IMID) patients showed a significant increase, whereas inflammatory arthritis (IA) or systemic lupus erythematosus (SLE) patients did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. IA patients on targeted-synthetic or biological disease-modifying antirheumatic drugs (ts/bDMARD), but not those on conventional-synthetic (csDMARD), had a greater prevalence despite a similar age distribution. ConclusionPatients with AI/IMID show a variable risk of hospital diagnosed COVID-19. Interplay of aging, therapies, and disease specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyze the specific factors involved in COVID-19 susceptibility.

IntroductionCost and drug toxicity often deter prolonged therapeutic use of anti-TNF agents in ankylosing spondylitis (AS). A planned study was completed to endorse our clinic-based observation of long-term relief following short-term administration of an anti-TNF agent. Methods50 consenting patients with symptomatic active chronic AS under rheumatology care in a community clinic were enrolled; naive for anti-TNF. 40 mg standard biosimilar Adalimumab (Bs-ADA, Exemptia) was injected subcutaneously every fortnight for six injections (10 weeks). Patients were monitored at several predetermined time points. Improvement was assessed with standard indices (Assessment Spondyloarthritis International Society/ASAS and Bath). An intention to treat analysis was performed: significant p <0{middle dot}05 ResultsPatients showed early and substantial significant improvement in pain, NSAID requirement, function, and in several indices (ASAS 20 & 40, ASAS partial remission, BASDAI, BASFI, ASDAS) which persisted after stopping injections. 84% and 52 % of patients respectively showed ASAS 20 improvement at weeks 12 and 48: corresponding to ASAS partial remission at 34% and 24%. Over 50% of patients maintained prolonged improvement and provided proof of concept (defined apriori). Serum Interleukin-6 assay showed a sharp reduction at 24 weeks. None developed TB or serious drug toxicity. 11 patients withdrew (mostly inadequate response). The absence of control was a limitation. ConclusionA ten-week administration of biosimilar adalimumab in difficult-to-treat AS showed early substantial improvement which often persisted for 24 weeks. This unconventional strategy was socioeconomically appealing. It merits further validation and acceptance, especially in resource strained settings.

BackgroundObesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). Among obese patients, abatacept was suggested as a preferable option to tumour necrosis factor alpha (TNF) inhibitors. Sex and gender differences in RA were described. ObjectivesTo assess the comparative effectiveness of etanercept, infliximab, and abatacept, compared to adalimumab, in patients with RA stratified by body mass index (BMI) and sex. MethodsObservational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). RA patients were classified in BMI-based cohorts: obese, overweight, and normal weight. Each BMI cohort was studied overall and stratified by sex. The study outcome was remission within 12-months, defined as a disease activity score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction (CARRAC). Logistic regression compared the effectiveness of etanercept, infliximab, and abatacept versus adalimumab. ResultsThe study included 443 obese, 829 overweight, and 1243 normal weight RA patients. Across the BMI cohorts, there were no significant differences in the odds of remission at [&le;]12-months for the study drugs compared to adalimumab. However, among females, an inverse effect for infliximab was found, whereby overweight patients had higher odds of remission, while obese patients had lower odds of remission, compared to the respective adalimumab users. ConclusionsDespite the previous hypothesis, treatment with abatacept showed similar odds of remission compared to adalimumab in all BMI cohorts. Conversely, compared to adalimumab, infliximab performed better in overweight female patients but worse in female patients with obesity. However, further validation is needed.

ObjectivesTo evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). MethodsSIGLEC1 was analysed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. ResultsSLE was confirmed in 76 of 232 patients (32.8%) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher compared to patients without SLE (p<0.0001). A sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 % and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were > 99.9 % and 0.1 %, respectively. Using ROC analysis and Delong testing, the area under the curve (AUC) for SIGLEC1 (AUC=0.95) was significantly higher than for ANA (AUC=0.88, p=0.031), C3 (AUC=0.83, p=0.001) and C4 (AUC=0.83, p=0.002) but not for anti-dsDNA antibodies (AUC=0.90, p=0.163). ConclusionIFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.

ObjectivesThe individual and socioeconomic burden of sarcopenia in rheumatoid arthritis (RA) is most relevant. However, longitudinal cohort data are scarce. MethodsProspective, single-center, controlled, observational cohort study of consecutive 124 postmenopausal women, 53 with RA, 71 healthy controls (HC). Low muscle mass and low muscle strengths was defined according to the European working group on sarcopenia in older people 2019 (appendicular lean mass index [ALMI] via dual-energy x-ray absorptiometry < 5.5 Kg/m2; handgrip strength via dynamometer < 16 Kg). Linear regression models were calculated including demographic and anthropometric data, comorbidities, and co-medication as confounders. ResultsMedian age was 63 (IQR 56, 70), follow-up 2.1 (IQR 2.0, 5.3) years. At baseline, median ALMI was 6.2 (IQR 6.0, 6.5) Kg/m2 in RA patients, 6.3 (IQR 5.6, 6.9) Kg/m2 in HC (p = 0.64) with no difference in rates of low muscle mass (RA 16.2 % vs. HC 15.1 %). In the fully adjusted model, mean change in ALMI per year was -0.05 (95%CI -0.10 to -0.01) Kg/m2 in RA patients and 0.00 (95%CI -0.02 to 0.03) Kg/m2 in HC resulting in a differential loss of -0.06 (95%CI -0.11 to -0.01) Kg/m2 per year (p = 0.027). For RA patients, the adjusted OR of experiencing any loss of muscle mass was 3.98 (95%CI 1.47 to 10.77) compared to HC (p = 0.007). On average, RA patients lost 0.78 % of muscle mass per year. At baseline, low grip strength was seen in 27.3 % of RA patients and in 2.9 % of HC (p = 0.002). In both groups, grip strength did not decline during study period. TNF inhibitors were associated with less, T-cell inhibition with greater loss of muscle mass. Low mass at baseline, disease duration and disease activity were not associated with loss of muscle mass. ConclusionPostmenopausal women with RA have a significant risk of accelerated loss of muscle mass over time.

BackgroundNationwide data at a country level on Covid-19 in unvaccinated patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are scarce. MethodsBy interlinking data from national electronic registries, covering nearly 99% of the Greek population (approximately 11,000,000), between March 2020 and February 2021, when vaccination became available, we recorded confirmed infections and Covid-19-associated hospitalizations and deaths in essentially all adult patients with RA, AS, PsA, SLE, and SSc under treatment (n=74,970, median age of 67.5, 51.2, 58.1, 56.2, 62.2 years, respectively) and in individually matched (1:5) on age, sex, and region of domicile random comparators from the general population. ResultsBinary logistic regression analysis after adjusting for age, sex and biologic agents, revealed that RA, PsA, SLE and SSc, but not AS patients, had significantly higher risk of infection (by 43%, 25%, 20% and 49%, respectively), and hospitalization for Covid-19 (by 81%, 56%, 94%, and 111%, respectively), possibly due, at least in part, to increased testing and lower threshold for admission. Patients with RA and SSc had indeed higher Covid-19 associated mortality rates [OR:1.86 (95% CI 1.37 to 2.52) and OR:2.90 (95% CI 0.97 to 8.67), respectively] compared to the general population. Each additional year of age increased the risk of hospitalization for Covid-19 by 3% (OR 1.030, 95% CI: 1.028 to 1.034) and the risk of Covid-19 related death by 8% (OR 1.08, 95% CI: 1.07 to 1.09), independently of gender, systemic rheumatic disease, and biologic agents. A further analysis using AS patients as the reference category, adjusting again for age, sex and use of biologic agents showed that patients with SSc had increased mortality (OR: 6.90, 95% CI: 1.41 to 33.72), followed by SLE (OR: 4.05 95% CI: 0.96 to 17.12) and RA patients (OR: 3.65, 95% CI: 1.06 to 12.54), whereas PsA patients had comparable mortality risk with AS patients. ConclusionComparing to the general population, Covid-19 may have a more severe impact in real-world patients with systemic rheumatic disease. Covid-19 related mortality is increased in subgroups of patients with specific rheumatic diseases, especially in older ones, underscoring the need for priority vaccination policies and access to targeted treatments.

ObjectivesPrimary objective was to investigate clinical features and biomarkers associated with severe systemic lupus erythematosus (SLE). The secondary objective was to identify patterns of SLE remission. MethodsA retrospective study of 200 SLE patients (2014-20) from ImmunoCure Center was conducted. Patients fulfilled ACR criteria 1997 for SLE classification. SLEDAI-2K categories mild-moderate (score <=10) and severe (score >10) were used as outcome for the primary objective. Predictors of severe SLE were evaluated by multivariate logistic regression analysis. For the secondary objective, we evaluated 94 records with follow-up time >1year. Remission status (Yes/No) was based on DORIS criteria. Survival regression was performed using Kaplan Meier curve. ResultsSignificant predictors of severe SLE were male gender (OR 4.1; 95% CI: 1.2, 13.5), oral ulcers (OR 6.9; 95% CI: 2.8, 17.1), alopecia (OR 2.1; 95% CI 1.0-4.1), nephritis (OR 4.5; 95% CI: 1.9-11.4), ESR >30mm/hour (OR 2.3; 95% CI: 1.2-4.4) and aCL antibodies (OR 2.4, 95% CI 1.0 -5.9). The mean duration of follow-up was 41{+/-}19 months. Remission on treatment was achieved in 66% of 94 patients, while off treatment in 21% with a mean post-remission follow-up of 18{+/-}15 months. For every one-month increase in the duration of follow-up, the hazard of time to remission increased by 4% (95% CI 0.95-0.98; P<0.001). Factor analysis identified 4 SLE subtypes. ConclusionA clinical model including aCL antibodies is presented here that predicts severe SLE. Remission is possible even in severe SLE in LMIC with adequate immunosuppression and persistent follow-up.

ObjectiveThe Coronavirus disease 19 (COVID-19) pandemic has led to widespread concerns about the risk of infection in patients with rheumatic diseases (RD) receiving disease modifying ant-rheumatic drugs (DMARDs) and other immunosuppressants (IS). MethodsA SurveyMonkey(R) based electronic survey was conducted amongst members of the Indian Rheumatology Association to understand the need for changes in prevailing practices. ResultsOf the 861 invitees, 221 responded. In the wake of the pandemic, 47.5% would reduce biological DMARDs (bDMARDs) while only 12.2% would reduce the use of conventional synthetic DMARDs. 64.2% were likely to defer change in IS, the reluctance being most with rituximab (58.3%) followed by cyclophosphamide (53.3%), anti-tumor necrosis factor alpha agents (52.4%) and Janus kinase inhibitors (34.39%). Hydroxychloroquine was the preferred choice (81.9%) for the treatment of COVID-19 followed by protease inhibitors (22.1%) and intravenous immunoglobulin (8.1%). Chloroquine was less preferred (19%). More than two-thirds (70.5%) believed that COVID-19 might trigger macrophage activation syndrome. Social distancing (98.1%) and hand hygiene (74.6%) were recommended by majority. 62.8% would avoid touch for clinical examination whenever feasible. ConclusionMost rheumatologists perceived the need to change treatment of RDs during the COVID-19 pandemic; reduce immunosuppression and defer the usage of rituximab and bDMARDs. Key messagesO_ST_ABSWhat is already known about this subject?C_ST_ABSPatients with rheumatic diseases receiving glucocorticoids, disease modifying ant-rheumatic drugs and other immunosuppressants have increased susceptibility to infections including respiratory tract infections What does this study add?{circ} There is an urgent need to revise the management of rheumatic diseases as perceived by a large group of practicing rheumatologists in India in the times of the COVID-19 pandemic. {circ}There is reluctance to initiate biological DMARDs (especially Rituximab and anti-TNF agents), tsDMARDs (JAK inhibitors) and cyclophosphamide. {circ}There is an inclination to prescribe hydroxychloroquine (HCQ) even for rheumatic diseases with weak level of evidence. How might this impact on clinical practice?This might identify areas to be addressed in a Delphi exercise to develop expert evidence to guide the management of RDs during the pandemic.

BackgroundPhysician Global Assessment (PGA) is a visual analogue score (VAS) that reflects the clinicians judgment of overall Systemic Lupus Erythematosus (SLE) disease activity. The aim of this systematic literature review (SLR) is to describe and analyse the psychometric properties of PGA. MethodsThis SLR was conducted by two independent reviewers in accordance with the PRISMA statement. All articles published until the 1st of July 2019 in Pubmed were screened with no limitation about years of publication, language or patients age. Psychometric properties data were analysed according to the OMERACT Filter methodology version 2.1. ResultsThe literature search identified 91 studies. Face validity was reported in all the articles retrieved, in which the PGA was used alone or as part of composite indices (SRI, SFI, LLDAS, DORIS remission criteria). Content validity was reported in 89 studies. Construct validity was demonstrated by a good correlation (r[&ge;]0.50) between the PGA with the SLEDAI (12 studies), SLAM (4 studies), LAI, BILAG and ECLAM (2 studies each). Criterion validity was assessed exploring the PGA correlation with quality of life measurements, biomarkers levels and treatment changes in 28 studies, while no study has evaluated correlation with damage. A good responsiveness for PGA was shown in 8 studies. A high variability in scales was found, causing a wide range of reliability (ICC=0.67-0.98). ConclusionPGA is a valid, responsive and feasible instrument, while its reliability was impacted by the scale adopted, suggesting the major need for a standardization of its scoring.

IntroductionThere is limited information on the effectiveness of COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods136 consecutive patients with rheumatic diseases who never had a diagnosis of COVID-19 previously, and had completed vaccination with either the ChAdOx1 or BBV152 vaccines were recruited. Their IgG antibody titres to the Spike protein were estimated 1 month after the second dose. Results102 patients had AIRD while the 34 had non-AIRD. Lesser patients with AIRD (92/102) had positive antibodies titres than ones with non-AIRD(33/34) [p<0.001]. Amongst patients who received the ChAdOX1 vaccine, the AIRD group had lower antibody titres. Although the AIRD patients receiving BBV152 had similarly lower titres numerically, this did not attain statistical significance probably due to lesser numbers. Comparing the two vaccines, 114(95%) of those who received ChAdOx1 (n=120) and 11(68.7%) of those who received BBV152(n=16) had detectable antibodies [p=0.004]. Antibody titres also were higher in ChAdOx1 recipients when compared to BBV152. To validate the findings, we estimated antibody titres in 30 healthy people each who had received either vaccine. All 30 who had received ChAdOX1 and only 23/30 of those who had received BBV152 had positive antibodies (p=0.011). ConclusionIn this preliminary analysis, patients with AIRD had lower seroconversion rates as well as lower antibody titres as compared to patients with non-AIRD. Also,the humoral immunogenicity of the BBV152 vaccine appears to be less than that of the ChAdOX1 vaccine. Validation using larger numbers and testing of cellular immunity is urgently required.

ObjectiveTo estimate COVID-19 infection incidence rate with severe affectation (requiring hospitalization) in patients with biological treatment due to rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), psoriasis (Ps), and inflammatory bowel disease (IBD) and compare it with incidence rate in the general population. MethodsRetrospective observational study based on information provided by two administrative databases. One of these two databases contains information on all patients seen in our hospital and diagnosed with COVID-19 infection between March 4th 2020 and April 26th 2020. The other database contains data from patients seen at Rheumatology, Dermatology and Digestive Departments in our hospital who are currently receiving biological therapy. We calculated the crude and age and sex adjusted incidence in both groups. To compare both groups we calculated the Incidence Rate Ratio. ResultsThere was a total of 2,182 patients with COVID-19 requiring hospitalization. Four patients out of a total of 797 patients receiving biological therapy had contracted COVID-19 and required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 1.41%, and it was 0.50% among the group receiving biological therapy. Rates adjusted by age and sex in the biological group was 0.45% (CI95% 0.11-4.13). The IRR of the group receiving biological therapy compared to the general population was 0.39 (CI95% 0.14-1, p=0.049). ConclusionFindings suggest that prior use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population. Key MessagesO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LICovid-19 susceptibility in patients with immune-mediated disorders and receiving treatment with biological therapy is unknown. C_LI What does this study add?O_LISevere manifestation incidence rate in patients with immune-mediated disorders receiving biological therapy treatment is not increased when compared to the general population. C_LIO_LIBiological therapies might protect patients from presenting severe COVID-19 manifestations. C_LI How might this impact on clinical practice?O_LIThese data could be used for current recommendations regarding management of patients receiving biological therapies. C_LI Mini AbstractThe objective of this study is to analyze the incidence rate of severe COVID-19 requiring hospital care for patients receiving biological therapy and to compare it to the general population. Patients treated with biological therapy have crude and adjusted incidence rates under those of the general population. Statement of Human and Animal RightsThis article does not contain any studies involving human participants or animals that were performed by the authors. For this type of study, formal consent was therefore not required.

BackgroundThe impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. MethodsIn this comparative cohort study, we identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. ResultsThe cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID were increased age (OR 5.31; CI 3.14-8.95), male sex (2.13; CI 1.35-3.36) and having an AI/IMID (OR 1.98; CI 1.15-3.41). ConclusionIn patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19.

BackgroundSulfasalazine induced cytopenia, nephrotoxicity, and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend three monthly monitoring blood-tests indefinitely while others recommend stopping monitoring after one year. To rationalise monitoring we developed and validated a prognostic model for clinically significant blood, liver, or kidney toxicity during established sulfasalazine treatment. DesignRetrospective cohort study. SettingUK primary-care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts. ParticipantsAge [&ge;]18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription. Study period01/01/2007 to 31/12/2019. OutcomeSulfasalazine discontinuation with abnormal monitoring blood-test result. Analysis: Patients were followed-up from six months after first primary-care prescription to the earliest of outcome, drug discontinuation, death, 5 years, or 31/12/2019.Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination. Results8,936 participants were included in the development cohort (473 events, 23,299 person-years) and 5,203 participants were included in the validation cohort (280 events, 12,867 person-years).Nine candidate predictors were included. The optimism adjusted R2D and Royston D statistic in the development data were 0.13 and 0.79 respectively. The calibration slope (95% confidence interval (CI)) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96-1.43) and 0.87 (0.67-1.07) respectively. ConclusionThis prognostic model for sulfasalazine toxicity utilises readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.<colcnt=1> Evidence before this study?O_LIHepatic, haematological, and renal toxicity from sulfasalazine occurs uncommonly after the first-few months of treatment. Nevertheless, the manufacturers and some specialist societies e.g., the American College of Rheumatology recommend monitoring blood-tests at three monthly intervals during established treatment. Other guidelines e.g., from the British Society of Rheumatology recommend no monitoring after the first two years of treatment. C_LIO_LIIt is not known whether hepatic, haematological, and renal toxicities due to sulfasalazine can be predicted and monitoring be risk-stratified. C_LI Added value of this study?O_LIThis study developed a prognostic model that discriminated patients at varying risk of sulfasalazine toxicity during long-term treatment. It had excellent performance characteristics in an independent validation cohort. C_LIO_LIThe model performed well across age-groups, and in people with rheumatoid arthritis and other inflammatory conditions. C_LIO_LIAny cytopenia or liver enzyme elevation prior to start of follow-up, chronic kidney disease stage-3, diabetes, methotrexate prescription, leflunomide prescription, and age were strong predictors of sulfasalazine toxicity. C_LI Implications of all the available evidenceO_LIThis prognostic model utilises information that can be easily ascertained during clinical visits. It can be used to inform decisions on the interval between monitoring blood-tests. C_LIO_LIThe results of this study ought to be considered by national and international Rheumatology guideline writing groups to rationalise monitoring during long-term sulfasalazine treatment. C_LI

Hydroxychloroquine (HCQ) is a conventional disease-modifying antirheumatic drug (DMARD), which is considered as relatively safe, and offers a modest efficacy profile for the treatment of inflammatory rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. In view of the anecdotal evidence on its immunomodulatory and anti-inflammatory properties, HCQ has been used as an off-label option in patients with osteoarthritis (OA), mainly for the treatment of inflammatory OA. Recently, many investigators have evaluated the safety and efficacy of HCQ for the treatment of OA in various randomized control trials (RCTs). While most RCTs have evaluated the HCQ in inflammatory OA (erosive hand OA), there are studies constituting knee OA patients as well. Currently, there are no systematic reviews that have summarized the evidence on the efficacy and safety of HCQ in OA population. Hence, this study aims to systematically review the evidence from RCTs assessing the efficacy and safety of HCQ for the treatment of OA. Biomedical databases such as PubMed, Embase, and Google Scholar will be searched to identify the RCTs of HCQ in patients with OA (hand, knee, hip, or any other OA). Cochrane risk of bias tool will be used to assess the quality of included studies. Review Manager 5 (Rev Man) and STATA Version 16 will be used to conduct the statistical analysis.