Unveiling cancer risk in ANCA-associated vasculitis: result from the Turkish Vasculitis Study Group (TRVaS).

To investigate cancer incidence in patients with ANCA-associated vasculitis (AAV), compare it with the age/sex-specific cancer risk of the Turkish population, and explore independent risk factors associated with cancer. This multicenter, incidence case-control study was conducted using the TRVaS registry. AAV patients without cancer history before AAV diagnosis were included. Demographic and AAV-related data of patients with and without an incident cancer were compared. Standardized cancer incidence rates were calculated using age-/sex-specific 2017 Turkish National Cancer Registry data for cancers (excluding non-melanoma skin cancers). Cox regression was performed to find factors related to incident cancers in AAV patients. Of 461 AAV patients (236 [51.2%] male), 19 had incident cancers after 2022.8 patient-years follow-up. Median (IQR) disease duration was 3.4 (5.5) years, and 58 (12.6%) patients died [7 with cancer and one without cancer (log-rank, p = 0.04)]. Cancer-diagnosed patients were older, mostly male, and more likely to have anti-PR3-ANCA positivity. The cumulative cyclophosphamide dose was similar in patients with and without cancer. Overall cancer risk in AAV was 2.1 (SIR) ((1.3-3.2), p = 0.004); lung and head-neck [primary target sites for AAV] cancers were the most common. In Cox regression, male sex and ≥ 60 years of age at AAV diagnosis were associated with increased cancer risk, while receiving rituximab was associated with decreased cancer risk. Cancer risk was 2.1 times higher in AAV patients than the age-/sex-specific cancer risk of the Turkish population population, despite a high rate of rituximab use and lower dose of cyclophosphamide doses. Vigilance in cancer screening for AAV patients covering lung, genitourinary, and head-neck regions, particularly in males and the elderly, is vital.

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.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

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.

Characterization of serum extracellular vesicles and their differential level of miR-197-3p in familial Mediterranean fever patients.

OBJECTIVES: The aim of this study was to analyze the existence of miRNAs derived from serum extracellular vesicles (EVs) in familial Mediterranean fever (FMF) patients. Our group has previously shown the association of certain miRNAs with FMF. METHODS: Serum samples of adult and pediatric FMF patients and their age matched controls were used in the study. Serum EVs were characterized by transmission electron microscopy (TEM) and flow cytometry. RNAs were isolated from EVs and levels of miR-197-3p and miR-20a-5p were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: EV characterization using TEM demonstrated fraction of 30-120 nm-sized particles with cup-shaped morphology. Flow cytometry results revealed the CD63 and CD81 positive populations as 53.3% in serum EVs. We showed that miR-197-3p and miR-20a-5p were "circulating miRNAs" and carried in EVs of FMF patients and controls. In FMF patients, level of miR-197-3p was significantly decreased. There was no significant alteration in the level for miR-20a-5p between patients and controls. CONCLUSION: We showed the differential level of miR-197-3p in serum EVs of the FMF patients. miR-197-3p's potential as a biomarker and therapeutic target in FMF pathogenesis warrants further investigation.

EVs and EV-miRNAs can be identified in FMF patients' sera.Serum EV-miR-197-3p is dysregulated in FMF patients.Serum EV-miR-197-3p might have both diagnostic and therapeutic potentials.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Behçet's syndrome: recent advances to aid diagnosis.

Behçet's syndrome is a recurring inflammatory multiorgan disorder affecting the skin, mucosa, eyes, joints, stomach, and central nervous system. Behçet's syndrome epidemiology varies greatly among populations (0.64-420/100,000), and Behçet's syndrome has gained increasing international acclaim in the recent 50 years due to raising awareness of the syndrome, although it is rare in most population. In addition to the unclear etiology of the syndrome, the diagnosis of Behçet's syndrome is complicated by a vague clinical presentation, phenotypic heterogeneity and/or incomplete representation, and the lack of any specific laboratory, radiographic, or histological findings. There exists a dire need to elucidate factors that contribute to disease pathogenesis and/or are associated with clinical features of Behçet's syndrome and the classification of different forms of the syndrome. The identification of such molecular, cellular, and/or clinical factors are crucial for timely diagnosis and efficacious management of Behçet's syndrome. We discuss recent advances in the clinical diagnosis of Behçet's syndrome and related contributions of genetics, epigenetics, microbiome, inflammasomes, and autoantibodies to the improved diagnosis, management, and understanding of Behçet's syndrome.

IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

Pulmonary hypertension in Behçet's disease: echocardiographic screening and multidisciplinary approach.

BACKGROUND: Little is known about the prevalence and causes of pulmonary hypertension (PH) in Behçet's disease (BD). This study was conducted to determine the prevalence and causes of PH in BD. METHODS: In this descriptive study, we screened 154 patients with BD for PH using transthoracic echocardiography between February 2017 and October 2017. An estimated systolic pulmonary arterial pressure (sPAP ≥ 40 mmHg) was used as the cutoff value to define PH. Patients with BD were categorized into 5 groups according to organ involvement including mucocutaneous/ articular, ocular, vascular, gastrointestinal, and neurologic involvement. Additional laboratory and imaging results were obtained from hospital file records to determine the causes of PH. RESULTS: PH was detected in 17 (11%) patients. Nine (52.9%) of these patients had group II PH (due to left heart disease), 4 (23.5%) had IV PH (due to pulmonary arterial involvement), and 1 had III PH (due to chronic obstructive lung disease). The frequency of PH was higher in BD patients with vascular involvement than those without (52.9% vs 28.5%; p = 0.04). Among 10 patients with pulmonary artery involvement (PAI) 4 (40%) had PH. Although the vascular BD group had the highest rate of PH, we observed no statistically significant difference in the frequency of PH between the predefined BD subgroups. DISCUSSION: : PH is not rare in patients with BD. The majority of BD patients with PH are in group II or IV PH. Patients with vascularinvolvement carry a higher risk for the development of PH. Monitoring BD patients with PAI should be considered for the development of group IV PH.

Characteristics and outcome of ANCA-associated vasculitides induced by anti-thyroid drugs: a multicenter retrospective case-control study.

OBJECTIVE: Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. METHODS: We performed a retrospective multicenter study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with 4 controls by gender and year of diagnosis. RESULTS: Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in 6 (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%), and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in 7 (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in 4 (11%). ATD were reintroduced in 7 cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs. 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs. 25%, P = 0.007), but less frequent kidney (38 vs. 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95%CI 0.01-0.65, P = 0.019). CONCLUSION: ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

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.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

The impact of antiphospholipid antibodies in Takayasu arteritis.

BACKGROUND: The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. METHODS: : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aß2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. RESULTS: Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aß2G1 and/or LA positivity. There were no patients with positive aCL. All aß2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aß2G1 (+) had a history of pregnancy loss. DISCUSSION: Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Tocilizumab in Behçet Disease: A Multicenter Study of 30 Patients.

OBJECTIVE: To evaluate tocilizumab (TCZ) efficacy in patients with refractory Behçet disease (BD). METHODS: This is a multicenter study of 30 patients fulfilling the international criteria for BD and treated with TCZ at different European referral centers. The clinical response was evaluated at 6 months from TCZ initiation. RESULTS: Ninety percent of patients with BD were refractory or intolerant to anti-tumor necrosis factor (anti-TNF) agents. Overall, TCZ was effective in 25 (83%) patients with BD of whom 18 (60%) and 7 (23%) were complete and partial responders, respectively. The complete response was 67%, 60%, and 42% in patients with uveitis (18/30), neurological manifestations (5/30), and mucocutaneous and/or articular (7/30) manifestations, respectively. TCZ had a significant steroid-sparing effect allowing patients to decrease their median daily prednisone dose from 20 (IQR 10-40) mg/day to 9 (IQR 5-13) mg at 6 months (P < 0.001). The number of patients with BD needing concomitant disease-modifying antirheumatic drug therapy fell from 7 (23%) to 4 (13%) at 6 months. Mild to moderate side effects were observed in 6 (20%) patients, and 3 (10%) presented with serious adverse events (pneumonia, intestinal perforation, and septicemia) requiring therapy discontinuation in 2 cases. CONCLUSION: TCZ seems to be an effective alternative to anti-TNF agents in treating BD-related uveitis and neurological manifestations.

Fertility, early menopause and pregnancy outcomes of patients with Takayasu's arteritis.

OBJECTIVES: The reproductive health of patients with Takayasu's arteritis (TA) is an important issue. Systemic inflammation and treatments used in TA may affect female reproductive organs, leading to infertility, maternal and fetal morbidity, and early menopause. This study aimed to evaluate fertility, early menopause and pregnancy outcomes of patients before and after TA diagnosis. In addition, pregnancy morbidities following TA diagnosis were analysed for each cluster. STUDY DESIGN: Two hundred and two patients with TA (184 females) who met the 1990 American College of Rheumatology criteria were registered in the prospective database of Hacettepe University Vasculitis Research Centre by the end of February 2020. Demographic and clinical features, comorbidities, distribution of vascular involvement, obstetric histories and outcomes were evaluated retrospectively. Patients with TA were classified according to novel proposed disease clusters. Early menopause was defined as menopause before 45 years of age. RESULTS: One hundred and twenty-one female patients with TA, for whom gynaecological records and marriage status could be obtained, were included in the study. Ninety-seven patients were married, of whom 12 (12.5 %) patients were infertile. In total, there were 238 pregnancies in 83 female patients with TA: 203 before TA diagnosis, 35 after TA diagnosis, and two patients were diagnosed during pregnancy. Compared with the pre-diagnosis group, maternal complications were significantly more common in the post-diagnosis group [23 (11.3 %) vs 9 (25.7 %); p = 0.048]. The most common maternal complication was gestational hypertension (12.1 %). Fetal complications were common in both groups (21.5 % pre-diagnosis vs 34.2 % post-diagnosis; p = 0.18), and included prematurity, intrauterine growth retardation and low birth weight. According to novel disease subsets, post-diagnosis patients were classified as C1 (n = 3, 15.7 %), C2 (n = 9, 47.3 %) or C3 (n = 6, 31.5 %). One patient could not be classified. There was no difference in obstetric outcomes between these subgroups. Early menopause was observed in 20 (16.5 %) of 121 patients, but some patients had not yet reached 45 years of age. CONCLUSION: Infertility was higher in patients with TA in comparison with the general population in Turkey (12.5% vs 8.6%), and the early menopause rate was lower in patients with TA (16.7% vs 36.1%). Pregnancies following a diagnosis of TA had more maternal complications than pre-diagnosis pregnancies. Fetal complications were more common both pre- and post-diagnosis. Chronic inflammation before TA diagnosis may lead to increased infertility and fetal complications.