Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.

OBJECTIVES: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). METHODS: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. RESULTS: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. CONCLUSION: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

OBJECTIVES: To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). METHODS: The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. RESULTS: Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). CONCLUSIONS: Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

Drug retention rate and predictive factors of drug survival for secukinumab in radiographic axial spondyloarthritis.

The drug retention rate has been an important indicator for evaluating the treatment tolerance. Unfortunately, our knowledge of the secukinumab retention rate in radiographic axial spondyloarthritis (r-AxSpA) is limited. The objective of this study was to assess the retention rate of secukinumab and evaluate predictive factors of drug survival based on data from a real-life cohort. We retrospectively assessed 147 r-AxSpA patients between May 2018 and January 2020 from the HUR-BIO database. Secukinumab retention rates were analyzed using the Kaplan-Meier method and Cox proportional hazard model was used for predictors factors. The global retention rate of secukinumab was 55% at 12 months. r-AxSpA patients with obesity had a lower frequency of secukinumab discontinuation (29% vs. 50%, p = 0.013) in comparison r-AxSpA patients without obesity. In multivariate analysis, multiple TNFi usage had a higher risk of secukinumab discontinuation [HR 1.99 (1.09-3.62), p = 0.024]; on the other hand, obesity had a lower risk [HR 0.45 (0.27-0.90), p = 0.008]. Except for not using multiple TNFi, this real-life analysis showed for the first time that obesity is not an adverse risk factor for secukinumab drug retention in r-AxSpA. Secukinumab, which is an interleukin-17A inhibitor, could act via a different pathway than tumor necrosis factor inhibitors (TNFi). The identification of predictive factors such as obesity that may affect the individual drug selection may provide more appropriate biologic treatment strategies for r-AxSpA.

Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Comprehensive assessment and outcomes of patients with chronic periaortitis.

OBJECTIVES: Chronic periaortitis (CP) is a less known but more frequently diagnosed fibro-inflammatory disorder, but we know little about it and data regarding follow-up and outcome are still very limited. This study aims to identify the clinicopathologic, laboratory, and radiologic features, as well as outcomes of CP patients. METHODS: Patients with CP from HUVAC database were included in the study. CP was diagnosed based on compatible imaging findings and histopathological evaluation (if available), in addition to clinical findings. Demographics, laboratory, clinical, and imaging data were retrospectively reviewed from medical records. RESULTS: A total of 51 (male/female:37/14) patients were included in the study. Median (IQR) age was 63 (53-69) years and follow-up duration was 40 (4-60) months. 32 of the patients were IgG4-related CP. The most common form of CP in our cohort was idiopathic retroperitoneal fibrosis (82%), followed by inflammatory abdominal aortic aneurysms (12%) and peri-aneurysmal retroperitoneal fibrosis (8%). 8 (15.6%) patients had thoracic periaortitis and 16 (31.6%) venous involvement. Cyclophosphamide (CYC) combined with steroids was the most preferred treatment modality (43%), followed by rituximab (RTX) (31.3%). Follow-up imaging was done after a median (IQR) of 7(3-11) months, 30% of the patients were stable and 64.1% showed regression. A total of 18 (35.2%) had been taken off therapy at the last visit. CONCLUSIONS: Idiopathic retroperitoneal fibrosis was the most frequent presentation, whereas 15.6% of patients had thoracic involvement. Venous involvement was also not uncommon. Optimal time for follow-up imaging was determined as 6-9 months. Steroids along with CYC/RTX had a favourable outcome in the treatment of these patients.

Is the impact of biologic agents in enteropathic spondylitis different from other spondylitis? Real life data from the HUR-BIO Registry.

OBJECTIVES: To compare enteropathic spondylitis (ES) with psoriatic spondylitis (PS) and ankylosing spondylitis (AS), in patients on biological disease-modifying anti-rheumatic drug (bDMARD) treatment. METHODS: Patients who were enrolled in the HUR-BIO registry were included. ES patients were considered as the main study group; AS and PS patients were included as the control groups. ES was defined as patients with inflammatory bowel disease (IBD) having inflammatory back pain/spine symptoms plus radiological sacroiliitis. RESULTS: Sixty-four ES patients (46.9% female), 128 AS patients (39.1% female), and 92 PS patients (62% female) were analysed. Baseline erythrocyte sedimentation rate (ESR) was significantly higher in the ES group than in the AS group. Both the baseline ESR and C-reactive protein were also higher in the ES group compared with the PS group. Among the first bDMARD use, infliximab use was higher in the ES group than the other groups. There was a marginal significant difference between the SpA subgroups in the retention rates of the first bDMARDs (log-rank, p=0.059). Ulcerative colitis was a significant predictor for switching of bDMARDs in comparison to Crohn's disease. Regarding the treatment responses, no significant differences were relevant for the three groups in terms of 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index score, the Assessment of Spondyloarthritis International Society partial remission score, and 20% improvement of ASAS score. CONCLUSIONS: A large majority of enteropathic spondyloarthritis patients on bDMARD treatment had radiographic sacroiliitis. ES patients had distinctive features that distinguish them from AS and PS patients.

Pleuroparenchymal fibroelastosis in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared. RESULTS: PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

Efficacy, retention, and safety of tofacitinib in real-life: Hur-bio monocentric experience

Background/aim: To assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients. Materials and methods: We analyzed all patients registered in the HURBIO database who received at least 1 dose of tofacitinib. Patients who received at least one dose were included in retention analysis; patients with at least 1 control visit were included in efficacy and safety analysis. Factors predicting good response at the last follow-up visit were analyzed by logistic regression analysis. Drug retention rates were calculated using the Kaplan­Meier method and predictors of drug retention were determined by Cox proportional hazard model. Adverse events, reasons for switching, and discontinuation were also determined. Results: Two hundred and forty-seven (210, 85.0% female) patients were included in the study. The median duration of tofacitinib treatment was 10.2 (20.2) [med, (IQR)] months. Two hundred and four (82.6%) patients were included in safety and efficacy analysis; 45.6% of patients were in low-disease activity (LDA) state (DAS28-CRP ≤ 3.2). Predictors of LDA were being biologic-naïve [aOR 2.53 (1.31­4.88); 95% CI] and RF negativity [aOR 2.14 (1.12­4.07); 95% CI]. At 1 year, the overall tofacitinib retention rate was 63.9% with no relevant predicting factor. Response and retention rates of tofacitinib were similar in patients with and without concomitant csDMARDs. Treatment failure was the most common cause of discontinuation. The most common infectious and laboratory adverse events were herpes zoster infection (3.9 per 100 patient-years) and elevation in ALT (x3UNL: 9.7 per 100 patient-years), respectively. Conclusion: Tofacitinib is effective as monotherapy or in combination with csDMARDs. It is a well-tolerated treatment option in Turkish RA patients.

Predictors of drug retention and treatment response in axial spondyloarthritis patients treated with certolizumab: real-life results from the HURBIO registry.

OBJECTIVES: To assess the real-life retention rate of certolizumab and factors related to retention of certolizumab. METHODS: We analysed all patients who received at least 1 dose of certolizumab and were registered in the HURBIO database. Patients with at least 1 control visit were included in efficacy analysis. Drug retention rates were calculated using the Kaplan-Meier method and predictors of drug retention was determined by Cox proportional hazard model. Factors predicting BASDAI50 response at first visit were analysed by the logistic regression analysis. Reasons of switching and discontinuation were also determined. RESULTS: A total of 325 (AS (76%), female 55%) patients were recruited. Median follow-up while receiving certolizumab was 13 (4.7-22.7) months. At 1 year, overall certolizumab retention rate was 72.5%. Predictors of poor certolizumab retention were: Current or ex-smoker [HR 1.11 (0.70-1.76), p=0.65], high CRP levels [HR 0.72 (0.45-1.16), p=0.18], biologic-naïve [HR 0.81 (0.49-1.32), p=0.39] and good BASDAI50 response at first control visit [HR 0.54 (0.30-0.96), p=0.04]. Mean duration from starting certolizumab to the first control visit was 3 (3-6) months. Predictors of poor BASDAI50 response: Presence of nr-axSpa [RR 2.12 (1.01-4.51), p=0.05], female gender [RR 2.14 (1.20-3.82), p=0.01] and history of biologic therapy [RR 3.52 (1.95-6.33), p<0.001]. The most common causes of drug switch were primary failure and drug side-effects. CONCLUSIONS: In this study, good BASDAI50 response at first visit seems to be a strong predictor of higher retention of certolizumab in patients with axial spondyloarthritis.

Do we consider enough the presence of triggering factors in the evaluation of patients with FMF? Triggering factors are highly prevalent in colchicine-resistant FMF patients.

The aim of the study is to investigate the frequency of triggering factors in colchicine-resistant and -responsive Familial Mediterranean Fever (FMF) patients as well as the effect of  interleukin (IL)-1 antagonist treatment on the triggering factors. Both colchicine-resistant (patients on IL-1 antagonist treatment) and colchicine-responsive (patients on colchicine who had ≤ 3 attacks in the last year) patients were questioned for the presence of 12 different triggering factors, including exposure to cold, emotional stress, fatigue, physical activity, menstruation (for females), sleeplessness, prolonged standing, long-duration travel, high-fat diet intake, starvation, infection, and trauma. Colchicine-resistant patients were questioned for the presence of triggering factors for two time periods, before and after treatment with IL-1 antagonists. We studied 28 colchicine-resistant and 35 colchicine-responsive patients. Overall 77.8% of patients had at least one triggering factor. Triggering factors were associated with 28.5% of the total number of attacks. More than half of the patients (57.1%) declared that they had avoided these conditions. The frequency of triggering factors was higher in the colchicine-resistant group as compared to the colchicine-responsive group (89.3% vs 68.6%; p = 0.04). In colchicine-resistant FMF patients, the frequency of triggering factors (89.3% vs 32.1%) and the percentage of attacks initiated by triggering factors (27.8 vs 14.4%; p < 0.001) were decreased after treatment with IL-1 antagonists. In this study, triggering factors were more frequent in colchicine-resistant patients as compared to colchicine-responsive patients. Treatment with IL-1 antagonists seems to increase the endurance of colchicine-resistant patients in stressful conditions.

Factors influencing the outcomes of non-pharmacological interventions for managing fatigue across the lifespan of people living with musculoskeletal (MSK) conditions: a scoping review protocol.

INTRODUCTION: Fatigue is an important and distressing symptom for many people living with chronic musculoskeletal (MSK) conditions. Many non-pharmacological interventions have been investigated in recent years and some have been demonstrated to be effective in reducing fatigue and fatigue impact, however, there is limited guidance for clinicians to follow regarding the most appropriate management options. The objective of this scoping review is to understand and map the extent of evidence in relation to the factors that relate to the outcome of non-pharmacological interventions on MSK condition-related fatigue across the lifespan. METHODS AND ANALYSIS: This scoping review will include evidence relating to people of all ages living with chronic MSK conditions who have been offered a non-pharmacological intervention with either the intention or effect of reducing fatigue and its impact. Databases including AMED, PsycINFO, CINAHLPlus, MEDLINE, EMBASE and Scopus will be searched for peer-reviewed primary research studies published after 1 January 2007 in English language. These findings will be used to identify factors associated with successful interventions and to map gaps in knowledge. ETHICS AND DISSEMINATION: Ethical approval was not required for this review. Findings will be disseminated by journal publications, conference presentations and by communicating with relevant healthcare and charity organisations.

Immunoglobulin G4-related thoracic disease: clinical and radiological findings of a Turkish cohort.

BACKGROUND AND AIM: Thoracic involvement of Immunoglobulin G4-related disease (IgG4-RD) is relatively rare and may be disregarded at the time of initial diagnosis due to its asymptomatic nature. This study aimed to ascertain the prevalence and patterns of thoracic involvement in a retrospective cohort of Turkish patients with IgG4-RD. METHODS: A total of 90 patients (47 males and 43 females, with a mean age of 57.7±15.5 years) diagnosed with IgG4-RD were reviewed retrospectively. All computed tomography (CT) scans were re-evaluated by two thoracic radiologists and IgG4-related thoracic disease was assessed on four compartments: The mediastinum, pulmonary parenchyma, airways, and pleura. IgG4-related thoracic disease was categorized as: definite, highly probable, probable or possible. RESULTS: There were 64 patients who had undergone at least one thorax CT examination, and 18 (28%) were diagnosed with IgG4-related thoracic disease. The rate of IgG4-related thoracic disease increased by 20% and reached a ratio of 48.4% (n=31) after a thorough reevaluation of registry data specifically to thoracic findings. The mediastinum was the most frequently involved compartment, affecting 16 (51.6%) patients, followed by pulmonary parenchyma in 14 (45.2%) patients, and airways and pleura in 10 (32.3%) patients each. Other organ involvements were more prevalent and IgG4 levels were higher in patients with thoracic involvement. Eosinophils were significantly elevated in patients with thoracic involvement (p=0.023). CONCLUSIONS: IgG4-related thoracic disease is heterogeneous and likely to be more prevalent than currently recognized. The mediastinum is the most frequently involved compartment. It is important to assess IgG4-related thoracic disease at the time of initial diagnosis. Elevated levels of serum IgG4 and eosinophils, as well as a greater number of organ involvements may serve as indicators of thoracic involvement.

Factors that predict development of chronic kidney disease in patients with rheumatoid arthritis receiving biologic DMARDs and mortality rates.

OBJECTIVES: We aimed to determine the choice of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/ts-DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts-DMARDs. METHODS: Two thousand one hundred forty-one RA (79.4% female) patients were included in the analysis from the HUR-BIO prospective registry. Patients were divided into the CKD group and the non-CKD group. Age and gender-matched patients were selected from the non-CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups. RESULTS: CKD was detected in 90/2141 (4.2%) RA patients on b/ts-DMARDs. Forty patients (2.3%) developed CKD during follow-up after the initiation of b/ts-DMARDs. In the CKD group, anti-TNF agents were chosen as the first-line b/ts-DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS-28-ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts-DMARDs. The mortality rate in RA-CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic. CONCLUSION: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts-DMARDs. While there was no significant difference in mortality rate between CKD and non-CKD patients, the overall mortality rate increased after the COVID-19 pandemic duration in both groups.

Relationship Between Ultrasound and Physical Examination in the Assessment of Enthesitis in Patients With Spondyloarthritis: Results From the DEUS Multicenter Study.

OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

Efficacy of non-pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of randomised controlled trials (RCTs) including adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction and synthesis were performed by two reviewers independently. Data were pooled in meta-analyses. RESULTS: From a total of 4150 records, 454 were selected for full-text review, 82 fulfilled the inclusion criteria and 55 RCTs were included in meta-analyses. Physical activity or exercise was efficacious in reducing fatigue in rheumatoid arthritis (RA) (standardised mean differences (SMD)=-0.23, 95% CI=-0.37 to -0.1), systemic lupus erythematosus (SLE) (SMD=-0.54, 95% CI=-1.07 to -0.01) and spondyloarthritis (SMD=-0.94, 95% CI=-1.23 to -0.66); reduction of fatigue was not significant in Sjögren's syndrome (SMD=-0.83, 95% CI=-2.13 to 0.47) and systemic sclerosis (SMD=-0.66, 95% CI=-1.33 to 0.02). Psychoeducational interventions were efficacious in reducing fatigue in RA (SMD=-0.32, 95% CI=-0.48 to -0.16), but not in SLE (SMD=-0.19, 95% CI=-0.46 to 0.09). Follow-up models in consultations (SMD=-0.05, 95% CI=-0.29 to 0.20) and multicomponent interventions (SMD=-0.20, 95% CI=-0.53 to 0.14) did not show significant reductions of fatigue in RA. The results of RCTs not included in the meta-analysis suggest that several other non-pharmacological interventions may provide a reduction of fatigue, with reassuring safety results. CONCLUSIONS: Physica activity or exercise and psychoeducational interventions are efficacious and safe for managing fatigue in people with I-RMDs.

Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses. RESULTS: From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results. CONCLUSIONS: Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.

The DETAIL questionnaire is a useful and effective tool to assess spondyloarthritis in patients with inflammatory bowel disease.

Introduction: This study aimed to determine the effectiveness of adding a simple questionnaire related to musculoskeletal system to routine outpatient examination to detect undiagnosed axial and peripheral arthropathy in patients with inflammatory bowel disease (IBD). Materials and methods: A musculoskeletal symptom questionnaire was given to all patients with IBD during their follow-up examinations between January 2020 and November 2021. The DETAIL questionnaire consisting of six questions about the musculoskeletal system was administered by asking the patients with IBD. All patients who answered yes to at least one of these questions were directed to specialists in the rheumatology department to undergo a detailed examination. The patients who were diagnosed with rheumatological disease after further investigation were recorded. Patients with a known diagnosis of rheumatological disease were excluded from the study. Findings: There were 333 patients with IBD included in the study. Of these patients, 41 (12.3%) had a previously diagnosed rheumatological disease and were excluded from the evaluation. Of the remaining 292 patients (147 with ulcerative colitis, 139 with Crohn's disease and six with indeterminate colitis; mean age 42 years), 67 (23%) answered yes to at least one of the questions and were referred to a rheumatology consultation. Rheumatological examination was completed in 52 patients. As a result of the evaluations, 24 patients (8.2%) were diagnosed with enteropathic arthritis (14 axial, 9 peripheral, and 1 axial plus peripheral). Patients with newly diagnosed enteropathy had a lower median disease age than patients without enteropathy. Conclusion: The DETAIL questionnaire is an effective and easy tool for identifying missed cases of SpA in patients with IBD.