Sex and body mass index impact on digit circumference for Leeds Dactylitis Index calculation.

OBJECTIVES: To estimate digit circumference and the impact of sex and body mass index (BMI) for the calculation of the Leeds Dactylitis Index (LDI) in psoriatic arthritis (PsA) patients with bilateral dactylitis. METHODS: Digit circumference of the hands and the foot were measured with a dactylometer and were studied according to sex and BMI (divided in 4 weight categories) in healthy Portuguese subjects, using Student's t-test and One-way ANOVA, respectively. The effect size of sex and BMI were calculated using Cohen's d test and Eta squared, respectively. Multiple linear regression was used to calculate the effect of sex and BMI, as well as their interaction, to create a formula to predict digit circumference. RESULTS: Fifty-nine participants (33 women, 26 men) with a mean BMI of 24.8 were included. Men's mean digit circumferences were statistically higher than those of women (p<0.001), with a large sex effect size in most of the digits. Differences in the mean circumference between the four BMI categories were statistically significant (p<0.05) for all digits, with a large BMI effect size. Sex and BMI were independent variables to predict mean digit circumference (p<0.001). A new tool (based on regression analysis) allowing to estimate the circumference of digits for males and females of different BMIs is presented. CONCLUSIONS: Our data allows the calculation of digit circumference for males and females of different BMIs in the Portuguese population; and shows that BMI influences digital circumference supporting BMI inclusion in LDI references tables.

Septic Polyarthritis by Staphylococcus aureus of "Unknown Origin".

ABSTRACT: More than 90% of septic arthritis cases are monoarticular. Joint infection can occur through several mechanisms such as hematogenous dissemination, by contiguity from adjacent infected soft tissue, surgical contamination, direct inoculation, or joint trauma.We report the case of a 69-year-old man admitted to our hospital with septic polyarthritis. The presented case is remarkable given its atypical presentation. The patient had no known risk factors for septic arthritis, comorbidities, or history of recurrent infections that could suggest some degree of immunosuppression. The atypical polyarticular involvement at presentation, the absence of sustained fever, and the good general condition of the patient delayed the diagnosis and treatment.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS: Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS: After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION: bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.

Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Predictive factors of fragility fractures and associated mortality: assessment of patients observed at emergency department.

AIM: To assess the predictive factors for a subsequent fragility fracture (FF) and mortality. METHODS: Retrospective monocentric study including patients observed at the emergency department (ED) of a referral hospital with a FF, between 1st January 2017 and 31st December 2018. Fractures events were identified through discharge codes using the 9th International Classification of Diseases codes and FF were adjudicated after revision of the clinical files. We identified 1673 patients with FF. After calculating a representative sample (95% confidence interval), 172 hip, 173 wrist and 112 vertebral fractures were included in the analysis. Their clinical files were reviewed until 31st December 2020. A multivariate analysis was performed in order to identify predictive factors for FF. RESULTS: Overall, during the follow-up period 76 patients (16.6%) had a new FF and 120 patients (26.3%) died. Multivariate analysis showed that previous visits to the ED due to falls (p=0.002) and malignancy (p=0.026) were independent risk factors for a new FF. The main predictors of mortality were age, hip fracture, oral corticosteroid treatment, normal or low BMI and cardiac, neurologic or chronic kidney disease. CONCLUSIONS: FF are a very prevalent public health problem that can lead to significant morbidity and death. Certain comorbidities seem to be associated with new FF and increased mortality. There might be a substantial missed opportunity for intervention in these patients, namely in ED visits.

Barriers and alternatives to pediatric rheumatology referrals: a survey of family doctors and pediatricians in Portugal.

BACKGROUND: Access to pediatric rheumatology (PR) is not well described in Portugal. The main goal of this study was to ascertain barriers to PR referrals and subsequent alternative referral patterns among family doctors and pediatricians. METHODS: A web-based survey was e-mailed to family doctors and pediatricians practicing in Portugal, in order to investigate access to PR care issues. Descriptive and comparative analysis was performed. RESULTS: Two hundred and ninety-two responses were obtained, 24.7% from pediatricians and 75.3% from family doctors. Only 12% claimed to have had specific education on PR. Nearly 70% worked less than one hour away from a PR center. Twenty eight percent had referred a patient to PR at least once, and 9.3% experienced a situation in which they considered referring to PR but ultimately did not. Many referred to other specialties, primarily pediatrics, adult rheumatology, and pediatric orthopedics. Pediatricians encountered more diversified rheumatic diseases. Fifty five percent had no opinion on PR centers' support, while 24% found it sufficient. Having specific training on PR, being a pediatrician and a specialist were associated with greater referrals to PR. The most rated measure for PR referrals' improvement was promoting education. Regional access to PR's discrepancies were documented. CONCLUSION: Mainly lack of education on PR, but also uneven national coverage and greater distances to some PR centers were the main barriers to PR referrals, in Portugal. Pediatricians seem to have better education, greater experience and more referrals to PR. The current alternatives for referral are pediatrics, adult rheumatology and pediatric orthopedics. Educational consolidation was the biggest and most rewarding inconsistency to battle against.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Osteoarthritis' shifting paradigm - are we evolving?

Osteoarthritis is the most common type of arthritis. Nowadays, it can no longer be undertstood as a singularly abrasive and mechanical disease. With time, unveiling its mechanisms to the molecular aspect brings us close to the full comprehension of its diversity and syndrome-like behavior. Reinforcing the propagation of the updated scientific knowledge and changing the underlying mentalities will serve as a fast track to the better integration of this disease. Rightfully treating this epidemic is of the utmost relevance.

Predictive factors of relapse after methotrexate discontinuation in juvenile idiopathic arthritis patients with inactive disease.

OBJECTIVE: To identify predictive factors of relapse after discontinuation of Methotrexate (MTX) in Juvenile Idiopathic Arthritis (JIA) patients with inactive disease. METHODS: We conducted a prospective multicenter cohort study of patients diagnosed with JIA using real world data from the Portuguese national register database, Reuma.pt. Patients with JIA who have reached JADAS27 inactive disease and discontinued MTX before the age of 18 were evaluated. RESULTS: A total of 1470 patients with JIA were registered in Reuma.pt. Of the 119 bionaive patients who discontinued MTX due to inactive disease, 32.8% have relapsed. Median time of persistence (using the Kaplan-Meier method and log-rank tests) with inactive disease was significantly higher in patients with more than two years of remission before MTX discontinuation and in those who did not use NSAIDs at time of MTX discontinuation. In Cox regression analyses and after adjustment for age at diagnosis, MTX tapering and JIA category, the use of NSAIDs at the time of MTX discontinuation (HR, 1.98 95%CI 1.03-3.82) and remission time of less than two years before suspension (HR, 3.12 95%CI 1.35-7.13) remained associated with relapse. No association was found between JIA category or the regimen of MTX discontinuation and the risk of relapse. CONCLUSIONS: In this large cohort we found that the use of NSAIDs at the time of MTX discontinuation was associated with a two times higher likelihood of relapse. In addition, longer duration of remission before MTX withdrawal reduces the chance of relapse in bionaive JIA patients.

Effectiveness and safety of original and biosimilar etanercept (Enbrel® vs Benepali®) in bDMARD-naïve patients in a real-world cohort of Portugal.

OBJECTIVE: To compare the effectiveness and safety of original (Enbrel®) and biosimilar (Benepali®) etanercept in Biologic Disease-modifying Antirheumatic Drug (bDMARD)-naïve patients, measured by persistence rates over 36 months of follow-up. METHODS: A retrospective multicentre observational study using data collected prospectively from The Rheumatic Diseases Portuguese Registry (Reuma.pt) was performed, including patients with: age ≥ 18 years old; diagnosis of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Spondyloarthritis (SpA) (axial or peripheral) with active disease and biologic-naïve who initiated treatment with etanercept as the first line biological treatment after 2010. Kaplan-Meyer and Cox regression were used to calculate the persistence rate in treatment. Disease activity at baseline and follow-up data at 6, 12, 18 and 24 months of treatment were compared. Causes for discontinuing therapy were summarized using descriptive statistics. Statistical significance was assumed for 2-sided p-values <0.05. RESULTS: We included 1693 patients (413 on Benepali® and 1280 on Enbrel®): 864 diagnosed with RA, 335 with PsA and 494 with SpA. The 3-year persistence rates were not significantly different between both treatment groups in RA, PsA and SpA patients. In the adjusted Cox model, hazard ratios of discontinuation were not statistically different (p>0.05). The proportion of subjects in remission or low disease activity in each disease was similar in both groups. Overall, 535 (31.6%) patients discontinued etanercept (428 patients on Enbrel® and 107 patients on Benepali®). The major cause of discontinuation was inefficacy (57.8%). No differences for the occurrence of inefficacy or adverse effects were found between treatment groups. CONCLUSIONS: Benepali® and Enbrel® demonstrated similar effectiveness and safety in RA, PsA and SpA in our cohort of patients. These data corroborate that the original and biosimilar drugs have similar quality characteristics and biological activity.

Portuguese recommendations for the use of biological and targeted synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis - 2020 update.

OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Remission of Rheumatoid Arthritis and Primary Biliary Cholangitis After Treatment With Tocilizumab.

Rheumatoid arthritis (RA) is characterized by synovitis of multiple joints which if untreated progresses to joint destruction. Primary biliary cholangitis (PBC) is an autoimmune and progressive disease of the liver of unknown origin. About 1.8-5.6% of individuals with PBC have RA and patients with RA are at higher risk of developing PBC compared to the general population. We report a case of a 76-year-old man, with a history of PBC, and a recent RA diagnosis, in which tocilizumab therapy was effective in the control of RA and PBC, and a literature review was performed. This case, along with only one case published in literature in which tocilizumab was used in the treatment of RA and PBC, suggests that tocilizumab may be effective and safe in the treatment of RA in patients with PBC. Inhibition of IL-6 may also be effective in PBC treatment.

Biologic disease-modifying anti-rheumatic drugs and patient-reported outcomes in axial SpA: a systematic review and a call for action.

This paper is to assess the efficacy of different biologic DMARDs (bDMARDs) on several patient-reported outcomes (PROs) in randomized controlled trials (RCT) in axial spondyloarthritis (axSpA). A systematic literature review (SLR) was performed. MEDLINE (May 1, 2018) was used with the filters "published in the last 10 years" and "humans." The PICO criteria used were Patients: adults with radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA); Intervention: any bDMARD; Compararator: placebo (PBO)/any different drug; Outcome: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL), the EuroQol-5D (EQ-5D), the Short Form 36 Health Survey physical component summary (SF36-PCS), the Short Form 36 Health Survey mental component summary (SF36-MCS), and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). After screening 84 initial references and manually selecting other 9, 24 publications, assessing TNF inhibitors (TNFi) or IL17A inhibitors (IL17Ai) were selected. Four RCTs quantified the minimal clinical important difference (MCID) between treatment arms. Most of the RCTs compared the mean difference of PROs between different timepoints. Overall, the treatment arm was superior to the comparator. PROs were often underreported or highly heterogeneously presented. MCID was seldom mentioned. There is a need to raise the standard of care on SpA by aiming at remission and PRO associated improvements. In order to achieve this goal, the target must be clearly defined, reported, and tested.

ANCA-associated vasculitis in a patient with enteropathic spondylarthritis: a case report and literature review.

Coexistence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and inflammatory bowel disease (IBD) is rare (Sy et al. in Semin Arthritis Rheum 45:475-482, 2016). Nevertheless, we present a case of an AAV in a 53-year-old female with enteropathic spondylarthritis previously treated with tumor necrosis factor α inhibitors (TNFi). Management of vasculitis in a patient with IBD may be problematic due to the difficulty in distinguishing if the vasculitis is an extraintestinal manifestation of the IBD or a new coexistent entity. Moreover, in our report, the previous treatment with TNFi is a possible confounding factor due to the paradoxical effects induced by TNFi, including vasculitis (Ramos-Casals et al. in Curr Rheumatol Rep 10:442-448, 2008). The reported case alerts to the complexity in the management of patients with enteropathic spondylarthritis and vasculitis, as well as discusses the diversity of differential diagnosis in this particular clinical scenario.

Osteoporosis management during the COVID-19 pandemic - Position paper.

COVID-19 pandemic significantly increased the already large number of victims of osteoporosis in Portugal. Osteoporosis outpatient clinics were either closed or had limited presential appointments. Many hospitals reduced orthopaedic services to make space for patients with COVID-19. In addition, the volunteer or forced sedentarism, as imposed by the pandemic, increased the risk of falls and fractures drastically. It urges to intensify the current efforts to improve the management of bone health and to prioritize fragility fracture care and prevention. This paper addresses the challenges in osteoporosis management during the COVID-19 pandemic and provides guidance on osteoporosis management. This position paper is a joint initiative of several health professionals and patients dedicated to osteoporosis.

Prevalence and clinical manifestations of Erasmus syndrome in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Erasmus syndrome (ErS) is a rare entity in which Systemic Sclerosis (SSc) develops following exposure to silica, with or without associated silicosis. The objectives of this study were: 1) to evaluate the prevalence of ErS in our SSc cohort; 2) to characterize the cases; 3) to evaluate the clinical and laboratory characteristics of SSc in patients with (Ers) or without silica exposure. METHODS: Cross-sectional and analytical study. Sociodemographic, clinical and laboratory data were collected from all patients with SSc diagnosed in our department according to ACR / EULAR criteria. Data on professional activity and possible exposure to silica were obtained by phone interview. RESULTS: Among 48 patients with SSc, the prevalence of ErS was 16.7% (8/48). All cases identified were male, corresponding to 72.7% of men with SSc followed at our department. There was a statistically significant association between ErS and male gender (p.

Development and validation of psoriatic arthritis switch quality assessment tool (PASQAL) - an outcomes measurement tool to assess the quality of biologic switch decisions in psoriatic arthritis.

BACKGROUND: Switching between biologic therapies is a recommended strategy for Psoriatic Arthritis (PsA) patients that show an insufficient response or adverse events. Although the choice of the subsequent biologic may be dependent on many factors, assessing the quality of the switch decision is of utmost relevance. OBJECTIVES: To develop and validate two outcomes measurement tools (for patients with peripheral and axial PsA phenotypes) that address the quality of treatment decisions in PsA regarding the switch of biologic therapies in clinical practice. METHODS: A Task Force and an Expert Panel were specifically assembled for this purpose. The Psoriatic Arthritis Switch Quality Assessment tool (PASQAL) development comprised a modified-Delphi method in a four-step procedure: 1) literature search and experts' opinion collection about quality indicators for PsA management; 2) Delphi design to address the development of the measurement tool; 3) three Delphi questionnaire rounds; 4) final consensus meeting. This phase resulted in the definition of two measurement tools, one to evaluate the quality of biologic switch in peripheral (pPASQAL) and another one in axial PsA (axPASQAL). For the validation of PASQAL, 12 experienced rheumatologists were asked to evaluate and classify the biologic switch of 80 clinical cases (40 with predominant peripheral and 40 with predominant axial PsA). Clinical judgement was defined to be the "gold standard" against which the performance of PASQAL was assessed. The results were used to assess tools' performance (sensitivity/specificity analysis) and the agreement between the tools and the gold standard (Cohen's kappa). RESULTS: PASQAL consists of 6 domains (joint disease activity, dactylitis, enthesis, physical function, quality of life, and skin and nail manifestations), respective instruments and thresholds. The classification of the biologic switch was divided into three quality levels: "Good", based on treat-to-target thresholds; "Moderate", based on improvement from baseline; and the remaining as "Insufficient". pPASQAL was found to be highly sensitive (92%) with the "Good" quality level and specific (97%) with the "Insufficient" quality level. Whilst axPASQAL showed overall higher sensitivity and specificity for all quality levels, as well as a higher level of agreement between the tool and the gold standard than pPASQAL (k=0.87 vs k=0.71). CONCLUSION: PASQAL was developed and showed good criterion validity for the evaluation of the quality of switch in both peripheral and axial PsA phenotypes. These tools may be used in research as well as in clinical practice, to support rheumatologists in making more informed therapeutic decisions.