Clinical and persistent remission in anti-HMGCR immune-mediated necrotizing myopathy to a single cycle of rituximab - a case-based review.

Anti-HMGCR myopathy is an increasingly recognized immune-mediated necrotizing myopathy. However, there are currently no evidence-based treatments available, so case reports and clinical experience are used to guide current management. We report a case of a 49-year-old man, treated with atorvastatin, who presented to the emergency department with progressive proximal muscle weakness. Anti-HMGCR antibodies were detected, and muscle biopsy revealed necrotizing myopathy. Initially, therapy with high-dose glucocorticoids and methotrexate was started, but 12 weeks later, the patient developed clinical deterioration with dysphagia. Then, he was successfully treated with one cycle of rituximab along with physical therapy. The use of rituximab in immune-mediated necrotizing myopathy has been heterogeneously described in the literature but mostly in case reports. The European Neuromuscular Centre working group recommends the use of rituximab in refractory cases. However, some studies highlight the importance of early and aggressive treatment for this disease. Clinical prospective studies are necessary to make proper evidence-based recommendations.

Audiovestibular Involvement in Patients With Systemic Sclerosis.

INTRODUCTION: Audiovestibular dysfunction has been reported in many autoimmune connective tissue diseases, including systemic sclerosis (SSc). OBJECTIVE: To assess the prevalence and features of audiological and vestibular disturbances in SSc patients and evaluate their relationship with disease duration, clinical features, nailfold videocapillaroscopy pattern, and immunologic profiles. METHOD: A matched case-control study was conducted in a rheumatology clinic of a second-level hospital over 24 months. All patients underwent a detailed ear, nose, and throat examination, as well as audiometric and vestibular assessments, including pure tone audiometry, speech audiometry, immittance tests, and the Video Head Impulse Test. RESULTS: Thirty-five SSc patients and 24 healthy controls were included in the study. In the SSc group, subjective hearing loss was reported by 17.1% of patients, vertigo by 14.3%, tinnitus by 11.4%, and dizziness by 5.7%. Sensorineural hearing loss was identified in 42.9% of SSc patients, significantly higher than in the control group ( p = 0.013). There was no correlation between audiological manifestations and clinical symptoms, organ involvement, immunologic characteristics, and treatment. Vestibular dysfunction was detected in 60% of SSc patients, significantly higher than the control group ( p = 0.05). A significant correlation was found between abnormal Video Head Impulse Test and the presence of anti-RNA polymerase III and anti-Th/To antibodies ( p = 0.05 and p = 0.034, respectively). CONCLUSION: Our study revealed an increased prevalence of sensorineural hearing loss and vestibulopathy in SSc patients.

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study.

OBJECTIVES: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe. METHODS: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders). RESULTS: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates. CONCLUSION: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.

Two-Year Mortality Predictors in Fragility Fractures-A Medical Records Review Study.

PURPOSE: To evaluate two-year mortality predictors in all subtypes of fragility fractures. METHODS: Medical records review, single-center study with Portuguese patients with fragility fractures; A univariate analysis, with chi-square for categorical variables and parametric t-student and non-parametric Wilcoxon tests for continuous variables, was performed. Posteriorly, a survival analysis, with subsequent Cox regression was conducted to establish independent risk factors/ predictors of two-year mortality in fragility fractures. RESULTS: 758 patients were enrolled in the study. We found a total of 151 deaths within the first two years post-fracture. On Cox regression, older age [OR1.10 CI (1.05-1.11)], male sex [OR1.85 CI(1.24-2.75)], anemia at baseline [OR2.44 CI(1.67-3.57)], malignancy [OR4.68 CI (2.13-10.27)], and multimorbidity [OR1.78 CI(1.11-2.87)] were found as independent predictors for two-year post-fracture mortality. CONCLUSION: Our study suggests that male sex, older age, anemia, malignancy, and multimorbidity are mortality predictors in the first two years after fragility fractures, reinforcing the importance of comorbidity management in preventing or, at least, minimizing adverse outcomes following fragility fractures.

Hospitalization costs in Portugal among people with obesity: results from a nationwide population-based cohort 2011 to 2021.

Background: Obesity has been extensively studied over the years, primarily focusing on the physiological aspects of the disease. However, the general burden of obesity mainly the financial implications and its influence on hospitalization and length of stay have only recently garnered attention in the literature, particularly in the case of Portugal. Aim: This study aimed to investigate the association between obesity and hospitalizations in the Portuguese adult population and compare the average costs of hospitalization among participants with and without obesity. Methods: At baseline, the analytic sample consisted of 10,102 participants aged ≥18 years from the Portuguese population-based Epidemiology of Chronic Diseases Cohort (EpiDoC). Participants were then followed for up to 10 years from 2011 to 2021 in three more waves of data collection. Body mass index was derived from self-reported weight and height, and instances of hospitalization were self-reported by the participants. The associated costs for each hospitalization episode were categorized according to national legislation and valued according to the pricing for Diagnosis Related Groups. Results: Obesity was associated with more hospitalizations (for example, Obesity class I vs. normal weight: OR = 1.33 [1.14-1.55]). However, when the presence of multimorbidity was considered, this association diminished. While longer hospital length of stay was observed in individuals with higher obesity categories, this difference did not reach statistical significance. On average, the total hospitalization costs per patient with obesity amounted to €200.4 per year. Conclusion: Obesity is as a risk factor for hospitalizations and potentially with higher length of stay hospitalizations, with this effect being partially mediated by the concurrent presence of multimorbidity. Consequently, obesity constitutes an additional burden on healthcare systems. This underscores the imperative of implementing cost-effective prevention programs aimed at addressing and managing this significant public health concern.

Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis - relationship with the reason for withdrawal from the previous treatment.

OBJECTIVE: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). RESULTS: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. CONCLUSION: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

Anti-SSA Ro52 and anti-Ro60 autoantibodies: association with clinical phenotypes.

OBJECTIVES: Anti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) antibodies are clearly associated with connective tissue diseases (CTD), but the clinical significance of anti-SSA(Ro52) antibodies remains unclear. The aim of the present study was to analyse the disease phenotype of patients with anti-Ro52 and/or anti-Ro60 antibodies. METHODS: A multicentre, cross-sectional study was carried out of positive anti-Ro52 and/or Ro60 antibodies patients followed at 10 Rheumatology centres from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographicsand clinical data were compared between the 3 groups, by patients' medical chart review. Univariate analysis was performed and subsequently logistic regression was used to identify intergroup differences and calculate the odds ratio with a 95% confidence interval (95% CI). RESULTS: We included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2, and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Anti-Ro52 antibody alone was more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97), p<0.001; OR 2.2 (95% CI 1.28, 3.86), p<0.01]. In group 2, the diagnosis of undifferentiated CTD is more frequent than in the other groups. Group 1 was more frequently associated with inflammatory myositis than group 2 [OR 0.09 (95% CI 0.01, 0.33), p<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p<0.001]. Group 1 was also more frequently associated with arthritis (p<0.01), interstitial lung disease (p<0.01), and myositis (p<0.01). CONCLUSIONS: Anti-Ro52+ antibody alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ antibody is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+ antibody.

The impact of a Fracture Liaison Service after 3 years on secondary fracture prevention and mortality in a Portuguese tertiary center.

Despite the establishment of Fracture Liaison Services (FLS) worldwide, no study has evaluated their impact on the Portuguese population. Our work has shown that the implementation of an FLS is associated with a significant increase in OP treatment and a lower risk of secondary fracture. PURPOSE: Fracture Liaison Services (FLS) have been established worldwide, with positive effects on treatment, secondary fracture, mortality, and economic burden. However, no study has evaluated their impact on the Portuguese population. Therefore, we purposed to evaluate the effect of an FLS model in a Portuguese center on osteoporosis (OP) treatment, secondary fracture, and mortality rates, 3 years after a fragility fracture. METHODS: Patients over 50 years old, admitted with a fragility fracture, between January 2017 and December 2020, were included in this retrospective study. Patients evaluated after FLS implementation (2019-2020) were compared with those evaluated before (2017-2018) and followed for 36 months. Predictors of secondary fracture and mortality were assessed using a multivariate Cox regression model, adjusted to potential confounders. RESULTS: A total of 551 patients were included (346 before and 205 after FLS). The FLS significantly increased the rate of OP treatment, when compared with standard clinical practice (8.1% vs 77.6%). During follow-up, the secondary fracture rate was 14.7% and 7.3%, before and after FLS, respectively. FLS was associated with a lower risk of secondary fracture (HR 0.39, C.I. 0.16-0.92). Although we observed a lower mortality rate (25.1% vs 13.7%), FLS was not a significant predictor of survival. CONCLUSION: Implementing the FLS model in a Portuguese center has increased OP treatment and reduced the risk of secondary fracture. We believe that our work supports adopting FLS models in national programs.

Validation of the Portuguese Version of the Scleroderma Health Assessment Questionnaire.

The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test-retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test-retest reliability (ICC 0.61-0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = -0.688) and EQ-5D-5L index score (r = -0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = -0.628). Mental score correlations were smaller. With the exception of the Raynaud's VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients.

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching.

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.

Costs of incident non-hip osteoporosis-related fractures in postmenopausal women from a payer perspective.

Osteoporosis-related fractures lead to high morbidity, mortality, and healthcare costs among post-menopausal women. This study showed that incident non-hip osteoporosis-related fractures are frequent among women aged 50 + in Portugal, leading to excessive healthcare costs of €74 million per year, in a conservative scenario. PURPOSE: This study aimed to estimate the costs of incident non-hip osteoporosis-related fractures among postmenopausal women living in Portugal from a payer perspective. METHODS: The study includes women ≥ 50 years old who participated in the baseline assessment (2011-2013) and the first follow-up wave (2013-2015) of the Epidemiology of Chronic Diseases cohort, a Portuguese community-based longitudinal prospective study (n = 2,762). Incident non-hip osteoporosis-related fractures were defined as any self-reported low impact non-hip fractures since baseline. Healthcare resource utilization during the year following fracture was obtained from an informal panel of experts. The amounts of resources used were multiplied by the national tariffs practiced in the National Health Service (NHS) to obtain the cost per patient in the year following a wrist, vertebral, or other site fracture, which was subsequently multiplied by the estimated annual number of incident fractures to obtain the total annual cost of incident non-hip osteoporosis-related fractures among postmenopausal women. RESULTS: Each year approximately 5,000 wrist, 3,500 vertebral, and 39,000 other-site osteoporosis-related fractures occur in women aged 50 + in Portugal. Healthcare costs per patient in the year following fracture vary from €2,709.52 for vertebral fractures to €3,096.35 for other fractures. Non-hip incident osteoporosis-related fractures among 50 + women cost approximately €74 million per year. Among all healthcare services, physiotherapy represents the bulk of costs. CONCLUSIONS: This study pinpoints the relevance of preventing non-hip osteoporosis-related fractures, as these cost about €74 million per year in direct healthcare costs, a substantial impact on the budget of the Portuguese NHS.

Creation and Validation of the European Portuguese Version of the Systemic Lupus Erythematous Quality of Life Questionnaire.

(1) Background: Patients with systemic lupus erythematous (SLE) experience profound effects on health-related quality of life (HRQoL) that cannot be explained by objective indicators of mortality and morbidity. This study aimed to adapt the SLE Quality of Life (SLEQoL) questionnaire to the European Portuguese population and to assess its reliability and validity for patients with SLE. (2) Methods: Two independent translators translated the original version of the SLEQoL questionnaire into Portuguese. A back-translated version was produced. The Portuguese version of the questionnaire was reviewed and tested for validity and reliability. Cronbach's alpha and the internal validity index were calculated to verify the internal reliability and validity of the content. Rheumatologists filled out the SLE Disease Activity Score (SLE-DAS) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index SLICC/ACR-DI questionnaires. (3) Results: This study involved 180 patients, of which 93.8% were females. The results indicated very high internal consistency reliability (α = 0.949), low correlations between the SLEQoL and the SLE-DAS, a correlation between all SLEQoL dimensions and all SF-36 dimensions (except for "response to treatment" and "self-image"), and good correlation scores with both the EQ-5D-5L index and VAS. (4) Conclusion: The Portuguese version of the SLEQoL questionnaire is valid and reliable for the measurement of HRQoL in SLE patients.