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.

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.

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.

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.

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.

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.

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.

Extended autoantibody panel in Turkish patients with early-stage systemic sclerosis: Coexpressions and their influences on clinical phenotypes.

BACKGROUND/AIM: To investigate the frequency and clinical relevance of an extended autoantibody profile in patients with systemic sclerosis (SSc). MATERIALS AND METHODS: In this cross-sectional study, serum from 100 consecutive patients was subjected to indirect immunofluorescence (IIF) (HEp-20-10/primate liver mosaic) and Systemic Sclerosis Profile by EUROIMMUN to evaluate anti-nuclear antibodies (ANA) and autoantibodies against 13 different autoantibodies in patients with SSc less than 3 years. RESULTS: Ninety-three of 100 patients were positive for ANA by IIF. Fifty-three patients showed single positivity, 26 anti-topoisomerase antibodies (anti-Scl70 ab), 16 anticentromere antibodies (ACAs), six anti-RNA polymerase III antibodies (anti-RNAPIII ab), one anti-Ku antibody, one anti-PM/Scl100 antibody, two anti-PM/Scl75 antibodies, one anti-Ro52 antibody, whereas 32 patients had multiple autoantibody positivities. Among classic SSc-specific autoantibodies, anti-Scl70 and anti-RNAPIII abs showed the highest cooccurrence (n = 4). One patient was simultaneously positive for anti-RNAPIII ab and ACA, and one was positive for ACA and anti-Scl70 ab. The clinical features were not statistically different between single and multiple autoantibody-positivity for classic SSc-specific autoantibodies (ACA, anti-Scl70 ab, and anti-RNAPIII ab), except for digital ulcer in the multiantibody positive ACA group (p = .019). CONCLUSION: Based on our results, coexpression of autoantibodies is not uncommon in SSc patients. Although autoantibodies specific to SSc in early disease show generally known clinical features, it remains to be investigated how the coexpression of autoantibodies will affect clinical presentation.

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.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

INTRODUCTION: This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. METHODS: HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug (bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). RESULTS: Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6 years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65 years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). CONCLUSIONS: The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

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.

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.

COVID-19-associated arthritis: an emerging new entity?

The current COVID-19 pandemic raises several clinical challenges. Cases of COVID-19-associated arthritis have been reported, and inconsistently described as either COVID-19 viral arthritis or COVID-19 reactive arthritis. We aimed to review all the reported cases of 'COVID-19-associated arthritis', which we propose, is a better term to define the entire spectrum of new-onset arthritis believed to be associated with SARS-CoV-2 infection. We performed a systematic literature review using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to search for articles published up to 13 December 2021. We included cohort studies, case series and case reports describing patients diagnosed with COVID-19 reactive or viral arthritis by a physician, irrespective of fulfilment of classification criteria. To identify relevant studies, medical subject headings and keywords related to 'COVID-19/SARS-CoV-2 infection' and 'reactive arthritis' were used. Our search retrieved 419 articles, of which 31 were included in the review. A total of 33 cases were reported in these 31 articles, the majority being adults (28/33=85%) with peripheral joint involvement (26/33=79%). Most of the patients responded well to treatment and the disease was self-limiting. These 33 case reports describe a possible causal relationship between exposure to SARS-CoV-2 and the onset of arthritis. However, since these cases were reported during a pandemic, other aetiologies cannot be fully excluded. The exact mechanism through which SARS-CoV-2 might trigger arthritis is not fully understood and robust epidemiological data to support a causal relationship are still lacking.

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).

Predictors of remission in people with axial spondyloarthritis: A systematic literature review.

BACKGROUND: Achievement of remission is a desirable outcome and the identification of predictors of remission may aid in the clinical management of axial spondyloarthritis (axSpA). Our aim was to summarise predictors of remission in people with axSpA. METHODS: In this systematic literature review (SLR), we searched MEDLINE, EMBASE, and Cochrane CENTRAL from their inception to May 20, 2022, and 2020-2021 American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) meeting abstracts. We included randomized controlled trials and cohort studies in which prognostic factors associated with remission were investigated by multivariable analysis. RESULTS: The SLR comprised 21 articles from 4592 citations. Three studies investigated "sustained remission" (≥3 consecutive visits), while the other assessed "point remission" (at single points in time, varying from 12 weeks to 8 years). The most used remission criteria were Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (14 studies) and Assessment of SpondyloArthritis international Society partial remission criteria (11 studies). Younger age, HLA-B27 positivity, male gender, lower baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), lower baseline Bath Ankylosing Spondylitis Functional Index (BASFI), lower baseline ASDAS-C-reactive protein, treatment with tumour necrosis factor inhibitors (TNFi), and concomitant use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), were the most consistent predictors of remission. Additionally, shorter disease duration, lower Health Assessment Questionnaire for the spondyloarthropathies and TNFi naivety were predictors of remission in two studies. Other factors were found to be predictors of remission in one study only. CONCLUSIONS: Predictors of remission in axSpA were identified. However, many of these predictors were only identified in 1-2 studies. Considering the differences in study design, further well-designed prognostic studies are needed to confirm and allow generalisation of these predictors to the general axSpA population.

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.

Biologics for immunoglobulin A vasculitis: targeting vasculitis or comorbid disease?

In this study, we aimed to evaluate the clinical features and treatments, including the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in a large cohort of pediatric and adult immunoglobulin A vasculitis (IgAV). Since data on the use of bDMARDs in IgAV are very limited, we collated the reasons for use of bDMARDs during the disease course. Patients who were enrolled in the Hacettepe University Vasculitis Research Centre (HUVAC) registry were included. In this prospective database dating from 2014, there were 436 IgAV patients classified as IgAV according to Ankara 2008 and/or American College of Rheumatology 1990 criteria. 88 adults and 330 pediatric IgAV patients were included as the main study group. Concomitant spondyloarthritis (SpA) was observed only in adult patients (10% vs 0% in children, p < 0.001). IgAV relapse was more common in adults than in children (p: 0.017). Adult patients were mostly treated with corticosteroid (p < 0.001) and conventional synthetic disease-modifying anti-rheumatic drug treatment (< 0.001), while more than half of the pediatric patients were followed up without immunosuppressive treatment. Ten (11%) adult patients used biologics. Among them, two patients used rituximab due to IgAV disease activity, three used infliximab due to SpA, three used etanercept due to SpA (one patient had a pediatric onset enthesitis-related arthritis), and two used anakinra due to recurrent familial Mediterranean fever attacks. This is the first study evaluating the use of all bDMARDs for any reason in the IgAV cohorts in the literature. None of the pediatric patients used biologics. Our data suggest biologics are mainly used for comorbid inflammatory diseases over refractory vasculitis in adult IgAV.

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.

Anxiety levels before biologic initiation and changes with treatment in patients with psoriatic arthritis: HUR-BIO biologic registry results.

OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease related to several comorbidities. Anxiety is an important comorbidity in PsA and the data is scarce. We aimed to understand the rates before biologic agents and change in anxiety with the treatment. METHODS: PsA patients from the Hacettepe University biologic database (HUR-BIO) were assessed for the high anxiety level (score ≥ 4) using the patient self-reported measure of anxiety on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). The rate and scores of anxiety were determined before starting biologic agents, at the first visit within 6 months. Changes in anxiety scores were assessed according to favorable treatment responses, and the correlation was evaluated by Spearman correlation analysis. RESULTS: From 520 patients registered, 147 [mean (SD) age 43.3 (12.4) years, 70.7% female] had anxiety score both at baseline and first visit within 6 months. Both the frequency of high anxiety level and mean (SD) scores decreased at the first visit [63.9% vs. 41.4%, 4.8 (3.4) vs. 3.2 (3.1) respectively, p < 0.001 for both] after a mean (SD) follow-up of 105.7 (22.2) days. There was also a positive correlation between the change in anxiety scores and all parameters tested for treatment response: pain, PGA, BASDAI, HAQ-DI, DAS-28, and also PsAID-12. CONCLUSION: Anxiety is a more frequent problem at biologic initiation than rates observed in the general PsA population. The rates show a decreasing trend and correlates with treatment response but is still high within 6 months under treatment. KEY POINTS: • As high as 65% of patients had a high anxiety levels before the initiation of bDMARDs. • The disease activity control is essential in reducing anxiety; however, rates are still high within 6 months. • Decreased anxiety scores and rates of the high anxiety level are linked to better outcomes.