Comparison of methotrexate and azathioprine as the first-line steroid-sparing immunosuppressive agents in patients with Takayasu's arteritis.

BACKGROUND: Immunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs). However, there is limited data comparing the efficacy and outcomes of different IS agents for this purpose. OBJECTIVES: In this study, we aimed to compare the outcomes of two most frequently used first-line IS agents, namely methotrexate (MTX) and azathioprine (AZA) in TAK patients. METHODS: TAK patients who received any IS agent in addition to GCs as the initial therapy were included in this multicentre, retrospective cohort study. Clinical, laboratory and imaging data of the patients were assessed. In addition, a matched analysis (cc match) using variables 'age', 'gender' and 'diffuse aortic involvement' was performed between patients who received MTX or AZA as the first-line IS treatment. RESULTS: We recruited 301 patients (F/M: 260/41, mean age: 42.2 ± 13.3 years) from 10 tertiary centres. As the first-line IS agent, 204 (67.8 %) patients received MTX, and 77 (25.6 %) received AZA. Less frequently used IS agents included cyclophosphamide in 17 (5.6 %), leflunomide in 2 (0.5 %) and mycophenolate mofetil in one patient. The remission, relapse, radiographic progression and adverse effect rates were similar between patients who received MTX and AZA as the first-line IS agent. Vascular surgery rate was significantly higher in the AZA group (23% vs. 9 %, p = 0.001), whereas the frequency of patients receiving ≤5 mg/day GCs at the end of the follow-up was significantly higher in the MTX group (76% vs 62 %, p = 0.034). Similarly, the rate of vascular surgery was higher in AZA group in matched analysis. Drug survival was similar between MTX and AZA groups (median 48 months, MTX vs AZA: 32% vs 42 %, p = 0.34). IS therapy was discontinued in 18 (12 MTX, 6 AZA) patients during the follow-up period due to remission. Among those patients, two patients had a relapse at 2 and 6 months, while 16 patients were still on remission at the end of a mean 69.4 (±50.9) months of follow-up. CONCLUSIONS: Remission, relapse, radiographic progression and drug survival rates of AZA and MTX were similar for patients with TAK receiving an IS agent as the first-line f therapy. The rate of vascular surgery was higher and the rate of GC dose reduction was lower with AZA compared to MTX at the end of the follow-up.

Frequency and the effects of spondyloarthritis-spectrum disorders on the clinical course and management of Takayasu arteritis: an observational retrospective study.

OBJECTIVES: Extravascular findings of Takayasu arteritis (TAK) often share features with the spondyloarthritis (SpA) spectrum of disorders. However, the characteristics of this overlap and its effect on the vascular manifestations of TAK are not fully known. Therefore, we aimed to investigate the frequency of SpA-related features in TAK patients. MATERIAL AND METHODS: In this observational retrospective study, 350 patients with TAK classified according to ACR 1990 criteria, from 12 tertiary rheumatology clinics, were included and evaluated for the presence of axSpA, IBD, or psoriasis. Demographic, clinical features, angiographic involvement patterns, disease activity, and treatments of TAK patients with or without SpA were analyzed. RESULTS: Mean age was 45.5 ± 13.6 years and mean follow-up period was 76.1 ± 65.9 months. Among 350 patients, 31 (8.8%) had at least one additional disease from the SpA spectrum, 8 had IBD, 8 had psoriasis, and 20 had features of axSpA. In the TAK-SpA group, TAK had significantly earlier disease onset, compared to TAK-without-SpA (p = 0.041). SpA-related symptoms generally preceded TAK symptoms. Biological treatments, mostly for active vasculitis, were higher in the TAK-SpA group (70.9%) compared to TAK-without-SpA (27.9%) (p < 0.001). Vascular involvements were similar in both. CONCLUSION: Our study confirmed that diseases in the SpA spectrum are not rare in TAK. Vascular symptoms appeared earlier in such patients, and more aggressive therapy with biological agents was required in the TAK-SpA group, suggesting an association between TAK and SpA spectrum. Key Points • The pathogenesis of Takayasu arteritis is mediated by an MHC class I alelle (HLA-B*52), similar to spondyloarthritis-disorders. • Extravascular findings of Takayasu arteritis are in the spectrum of spondyloarthritis disease. • This frequent coexistence between Takayasu arteritis and spondyloarthritic disorders suggests a relationship rather than a coincidence.

Divergent perspectives: exploring the relationships between St. George's Respiratory Questionnaire and outcome measures in systemic sclerosis-associated interstitial lung disease.

INTRODUCTION/OBJECTIVES: Controversy exists regarding the concordance of patient-reported outcome measures (PROMs) with other assessment parameters in systemic sclerosis-associated interstitial lung disease (SSc-ILD). This study aims to explore the association between the St. George's Respiratory Questionnaire (SGRQ) and various outcome measures in patients with SSc-ILD within a real-world cross-sectional setting. METHOD: Patients with SSc-ILD were consecutively recruited from our SSc cohort. Simultaneous administration of SGRQ, scleroderma Health Assessment Questionnaire (sHAQ), respiratory visual analog scale (R-VAS), pulmonary function tests (PFTs), and the 6-min walking test (6-MWT) was conducted. The total extent of lung fibrosis was quantified using high-resolution computed tomography (HRCT) images. Relationships between SGRQ and functional, radiographic, and other patient-reported outcome measures were analyzed. RESULTS: The total SGRQ score demonstrated correlations with forced vital capacity (FVC) and R-VAS (r = - 0.397, p = 0.016 and r = 0.418, p = 0.027, respectively). Symptom score correlated with ILD-extension (r = 0.430, p = 0.005); activity score correlated with FVC and R-VAS (r = - 0.502, p = 0.002 and r = 0.395, p = 0.038, respectively); impact score correlated with R-VAS (r = 0.386, p = 0.043). In patients with fibrosis extent exceeding 20%, total SGRQ score was associated with sHAQ and R-VAS (r = 0.398, p = 0.049; r = 0.524, p = 0.021, respectively), activity score with R-VAS (r = 0.478, p = 0.038), and impact score with 6-MWT-D and R-VAS (r = - 0.489, p = 0.034; r = 0.545, p = 0.016, respectively). The symptom score and activity score demonstrated optimal performance in identifying patients with interstitial lung disease (ILD) extent exceeding 20% and forced vital capacity (FVC) less than 70% (area under the curve [AUC] 0.799, p = 0.002, and AUC 0.792, p = 0.03, respectively). CONCLUSIONS: Our study reveals varying degrees of correlation between SGRQ and distinct outcome measures. Given the incomplete alignment of SGRQ with other outcome measures, an integrative approach utilizing existing criteria as complementary tools is recommended. Key Points • Patient-reported outcome measures (PROMs) derive from patients' subjective evaluations of the impact of the disease on their daily activities, social interactions, and psychological well-being. • PROMs frequently serve as outcome measures in randomized controlled trials, yet conflicting findings have emerged in relation to primary outcomes. • This study aims to assess the appropriateness and interrelation of PROMs with both radiological and functional outcome measures, providing insight into the current state of our patients in a real-life context. The investigation delves into the compatibility of these measures with each other.

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.

Gynecological symptoms in primary and secondary Sjögren's syndrome and the effect of the disease on sexuality.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune systemic disease affecting many organs and systems, such as genital system. AIM: This study aimed to present the gynecological symptoms of patients who were followed up in an outpatient clinic because of primary Sjögren's syndrome (pSS) and secondary Sjögren's syndrome (sSS) and to show how the disease affected sexuality. METHODS: This study is a cross-sectional study conducted between 2019 and 2020. The study sample consisted of 60 pSS patients, 42 sSS patients, and 52 healthy control subjects. OUTCOMES: All the participants were questioned about sexuality, and completed the 36-item Short Form Survey, Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, and Modified Hill questionnaire. RESULTS: The patients had a mean age of 55.6 ± 11.85 years in pSS, 59.39 ± 11.18 years in sSS, and 56.1 ± 10.46 years in healthy control subjects. Vaginal and vulvar dryness and dyspareunia were present at a significantly higher rate in SS, especially in pSS, compared with the control subjects. The Health Assessment Questionnaire score was significantly lower in the pSS group than in the sSS group. Arthralgia, myalgia, and fatigue were prominent in all SS patients. CLINICAL IMPLICATIONS: Gynecological symptoms, sexual ability, and the effects of the disease on sexuality should be questioned in all SS patients. STRENGTHS AND LIMITATIONS: It is very important that we evaluate the gynecological symptoms of both pSS and sSS patients and the effect of the disease on these symptoms. The small number of patients and healthy control subjects is a limitation. CONCLUSION: The gynecological and musculoskeletal symptoms negatively affected sexuality in patients with pSS and sSS, and the negative effect of the disease on sexuality was more pronounced in the pSS group.

Analysis of clinical, immunological characteristics, damage, and survival in 300 Turkish systemic lupus erythematosus patients.

OBJECTIVE: This retrospective study aimed to conduct a comprehensive analysis of Turkish Systemic Lupus Erythematosus (SLE) patients of Caucasian ethnicity, focusing on their clinical, immunological, and therapeutic characteristics, damage accural and mortality. PATIENTS AND METHODS: We carried out a retrospective assessment of 300 SLE patients diagnosed between 2001 and 2017 at Kocaeli University Rheumatology Clinic. Demographic data, clinical manifestations, immunological profiles, treatment approaches, disease-related damage, and survival information were collected. RESULTS: The study population had a significant female predominance (89%) with a mean age of disease onset of 35.4 (SD:13.3) years. Hematological (72.6%) and mucocutaneous (72%) manifestations were the most common clinical findings, followed by arthritis (66.3%). Females had higher frequency of photosensitivity (p = 0.019), malar rash (p < 0.001), and alopecia (p = 0.014). Anti-dsDNA antibodies were detected in 61.6% of patients, while 57% of patients had hypocomplementemia. Secondary antiphospholipid syndrome was observed in 15.3% of patients; the most common manifestations included deep venous thrombosis (32.6%) and cerebrovascular accidents (30.4%). Lupus Nephritis (LN) affected 40.3% of the cohort. The most common pathologic finding was Class IV LN (30.5%). Eventually, 13 (4.3%) patients developed chronic kidney disease (CKD) and 4 had renal replacement therapies. Patients with LN had higher usage of pulse steroids, azathioprin, mycophenolate mofetil, cyclophosphamide, and rituximab (p < 0.001 for each).  In the juvenile-onset group (n = 31, 10.3%), an increased occurrence of malar rash (p = 0.009), nephritis (p = 0.034), hypocomplementemia (p = 0.001), positive anti-dsDNA (p = 0.007), anti-Sm (p = 0.046), anti-rib-P (p = 0.014) antibodies were observed. At least one damage parameter was observed in 32.6% patients with musculoskeletal manifestations being the most common. Thirteen patients were diagnosed with various malignancies, with cervical cancer being the most common (4 cases). The total 5 and 10-year survival rates were 92.5% and 86.7%, respectively. However, patients with CKD, had lower survival rates; 75% at 3 years and 60% at 15 years. Regression analysis demonstrated an association of CKD and  history of infections with decreased survival (p = 0.02, each). CONCLUSION: Ethnicity and geography influence the clinical diversity of SLE. Recognizing these disparities is crucial for tailoring patient care. Future inception cohort studies in Turkish SLE patients are necessary to address the limitations of retrospective research.

Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

OBJECTIVE: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset. METHODS: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment. RESULTS: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years. CONCLUSION: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs.

Long-term efficacy of canakinumab in hyperimmunoglobulin D syndrome.

Hyperimmunoglobulin D syndrome (HIDS) is a rare autoinflammatory disorder with autosomal recessive inheritance. It is caused by specific mutations in the mevalonate kinase gene (MVK). No treatment specific to HIDS has been approved to date; however, nonsteroidal anti-inflammatory drugs, steroids, colchicine, tumor necrosis factor-α inhibitors, and anti-interleukin-1 treatments are used, based on case reports and observational studies. Herein, we report a case with recurrent fever and arthritis attacks who did not respond to anakinra and was successfully treated with canakinumab. Long-term remission was achieved without any side effects with 300 mg canakinumab treatment every 4 weeks for 5 years.

Does obesity affect treatment response to secukinumab and survival in ankylosing spondylitis? Real-life data from the TURKBIO Registry.

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS). METHODS: We performed an observational cohort study that included AS patients based on the biological drug database in Turkey (TURKBIO) Registry between 2018 and 2021. The patients were divided into three groups: normal [body mass index (BMI) < 25 kg/m2], overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2). Disease activity was evaluated at baseline, 3, 6, and 12 months. Drug retention rates at 12 months were also investigated. RESULTS: There were 166 AS patients using secukinumab (56.6% male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (P = .003). There was no statistically significant difference in Bath Ankylosing Spondylitis Disease Activity Index 50, Assessment of SpondyloArthritis international Society 20 (ASAS20), ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, and ASDAS clinically important improvement responses between the three groups at 3, 6, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (P > .05). CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

Radiological progression and predictive factors in psoriatic arthritis: insights from a decade-long retrospective cohort study.

OBJECTIVES: Radiological alterations in psoriatic arthritis (PsA) are an established phenomenon frequently observed throughout the disease course. Our goal was to investigate the changes in the bone structure of PsA patients by conventional radiography. METHODS: This study designed as a retrospective cohort study and cross-sectional evaluation for disease activity. The disease activity and the severity of skin and nail involvement were assessed. The Simplified Psoriatic Arthritis Radiographic Score (SPARS) was used to investigate the radiological progression. Logistic regression analysis was used to determine the predictors of radiological changes. RESULTS: Joint space narrowing and bone proliferation in hands (p = 0.001 and p = 0.001, respectively) and joint space narrowing in feet (p = 0.047) were more common at the final evaluation than at the baseline assessment. Total scores of joint space narrowing and bone proliferation in hands and feet were higher at the last visit than at the initial assessment (p < 0.001). Male gender (p = 0.030, OR 4.32 (95%CI 1.15-16.15)], older age (for joint space narrowing [p = 0.026 OR 1.08 (95%CI 1.01-1.56)] and for proliferation [p = 0.025 OR 1.08 (95%CI 1.01-1.44)]), high Disease Activity index for Psoriatic Arthritis (DAPSA) scores at baseline [p = 0.032 OR 6.21 (95%CI 1.17-32.92)], and symmetrical polyarticular involvement at baseline [p = 0.025 OR 5.3 (95% CI 1.23-22.4)] were found as predictors of structural changes. CONCLUSION: By the end of the decade, joint space narrowing and proliferation were observed to be more common than erosion. Male gender, older age, higher initial DAPSA scores, and initial polyarticular involvement were identified as predictors of radiological damage. Key Points • The radiological changes of Psoriatic arthritis are a well-known entity. However, studies investigating the progression of joint involvement over time are scarce. • This study reveals that joint space narrowing and proliferation are the most prominent radiological alterations in Psoriatic Arthritis patients at the end of the decade. • Male gender, older age, higher baseline DAPSA scores, and initial polyarticular involvement are predictive factors influencing the progression of bone destruction  in Psoriatic Arthritis patients.

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.

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.

Unintentional Monotherapy in Rheumatoid Arthritis Patients Receiving Tofacitinib and Drug Survival Rate of Tofacitinib.

OBJECTIVE: To determine the rate of unintentional monotherapy (UM; switching to monotherapy from combination therapy of patients' own volition) in rheumatoid arthritis patients receiving tofacitinib and to evaluate tofacitinib survival rate. METHODS: This national, multicenter study included patients' data from the TURKBIO Registry. Demographics, clinical characteristics, disease duration and activity, comorbidities, and treatments were analyzed. RESULTS: Data of 231 rheumatoid arthritis patients (84.8% female, median age, 56 years) were included; 153 were initially prescribed combination therapy and continued to their therapies; 31 were initially prescribed combination therapy but switched to monotherapy on their own volition (UM); 21 were initially prescribed monotherapy and switched to combination therapy; 26 were initially prescribed monotherapy and continued to their therapies. The rate of comorbidities at the time of data retrieval was higher in the UM group than in the combination group (83.3% vs. 60.3%, p = 0.031). Presence of comorbidities was a significant factor affecting switching to monotherapy ( p = 0.039; odds ratio, 3.29; 95% confidence interval, 1.06-10.18). The combination and UM groups did not differ regarding remission rate assessed by Disease Activity Score 28-joint count C-reactive protein (60.5% and 70%, respectively; p = 0.328). Drug survival rates of the UM and combination groups did not differ. The median drug survival duration of tofacitinib was 27+ months with 1- and 4-year drug survival rates of 89.6% and 60.2%, respectively, in the UM group. CONCLUSIONS: Although 13.4% of the study population started monotherapy unintentionally, drug survival and remission rates of the UM and combination groups were not different. Comorbidity was a factor affecting transition from combination therapy to monotherapy.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement.

Behçet's disease is a complex inflammatory vasculitis with a broad spectrum of clinical manifestations. The purpose of this study was to investigate the genetics underlying specific clinical features of Behçet's disease. A total of 436 patients with Behçet's disease from Turkey were studied. Genotyping was performed using the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic regressions adjusting for sex and the first five principal components were performed for each clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was calculated for each clinical feature. Genetic association analyses of previously identified susceptibility loci in Behçet's disease revealed a genetic association between ocular lesions and HLA-B/MICA (rs116799036: OR = 1.85 [95% CI = 1.35-2.52], p-value = 1.1 × 10-4). The genetic risk score was significantly higher in Behçet's disease patients with ocular lesions compared to those without ocular involvement, which is explained by the genetic variation in the HLA region. New genetic loci predisposing to specific clinical features in Behçet's disease were suggested when genome-wide variants were evaluated. The most significant associations were observed in ocular involvement with SLCO4A1 (rs6062789: OR = 0.41 [95% CI = 0.30-0.58], p-value = 1.92 × 10-7), and neurological involvement with DDX60L (rs62334264: OR = 4.12 [95% CI 2.34 to 7.24], p-value = 8.85 × 10-7). Our results emphasize the role of genetic factors in predisposing to specific clinical manifestations in Behçet's disease, and might shed additional light into disease heterogeneity, pathogenesis, and variability of Behçet's disease presentation across populations.

Disease severity and genotype-phenotype correlation in adult patients with familial Mediterranean fever.

OBJECTIVES: To assess the relationships of disease severity with genotype and phenotype in adult familial Mediterranean fever patients. METHODS: Two-hundred seventy-five patients included in the study were divided into four groups according to their mutations: Group 1, M694V homozygous; Group 2, M694V-other; Group 3, other-other; and Group 4, no meaningful gene variants. Disease severity was evaluated using the Pras disease severity score. The association between Pras scores and other possible predictors was assessed by the multiple linear regression analysis. RESULTS: In this study, 12.4% of all patients were in Group 1, 55.3% were in Group 2, 26.5% were in Group 3, and 5.8% were in Group 4. Pras scores were higher in Group 1 than in Groups 2, 3, and 4 (post hoc pairwise comparisons; P = .001, P < .001, and P = .001, respectively). Age at disease onset and age at diagnosis were found moderately and strongly correlated with Pras scores. Patients with moderate and severe disease were intensely involved in Group 1. CONCLUSIONS: Higher Pras scores, earlier age of symptoms and diagnosis, more frequent arthritis and erysipelas-like erythema, and higher colchicine dose are closely associated with M694V homozygous familial Mediterranean fever patients. These patients also have mostly moderate and severe disease severity.

A national, multicenter, secondary data use study evaluating efficacy and retention of first-line biologic treatment with tocilizumab in patients with rheumatoid arthritis in real-life setting: results from TURKBIO registry.

Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that targets the IL-6 receptor. TCZ found to be efficacious and has a good tolerated safety profile in rheumatoid arthritis (RA) patients. The aim of this study was to describe the disease activity and retention rate in Turkish RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting. Secondary data obtained from adult RA patients' files was used in a multicenter and retrospective context. Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints with ESR (DAS28-ESR), and retention rates of TCZ were evaluated at related time points. 130 patients (87.7% female) with a mean age of 53 years (SD; 15.0) were included in the study. Mean RA duration was 14 years and median duration of follow-up was 18.5 months. Number of patients with ongoing TCZ treatment at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (< 2.8) and DAS28-ESR (< 2.6) scores were 61.5, 44.6, 30%, and 54.6, 40.8, 27.7%, respectively. Both CDAI and DAS28-ESR scores significantly improved at 6, 12 and 24 months (p < 0.001 for both). At 24 months, 23 patients (17.6%) discontinued TCZ, of whom majority (17/23) were due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93, 84.3, and 72.2%, respectively. In this real-world study, TCZ as a first-line biologic therapy was found to be efficacious and showing high retention rates. These real-world study results are in line with previous randomized studies.

The respiratory manifestations in patients with primary Sjögren's syndrome: is interstitial lung disease related to disease activity?

BACKGROUND: Sjögren's syndrome is a systemic, autoimmune disease and can affect many organs and systems. In this study, we aimed to evaluate the respiratory manifestations, and the association between interstitial lung disease (ILD) and disease activity in primary SS (pSS) patients. METHODS: The study design was retrospective cross-sectional, and 151 patients followed up with a diagnosis of pSS between 2004 and 2019 were included in the study. Demographic and clinical data, laboratory results, chest radiographs and thorax computed tomography (CT) results were obtained from patient files and hospital imaging system. Thorax CT was requested from all patients with respiratory complaints and abnormalities in physical examination and pulmonary function test. Disease activity was calculated with EULAR pSS disease activity index (ESSDAI) and clinical European League Against Rheumatism SS Disease Activity Index (clin-ESSDAI). RESULTS: In our study, 97% of pSS patients were female, and the mean age was 55.9 ± 12 years, disease onset age was 45.5 ± 12.1 years, disease duration was 10.7 (1-38) years. According to CT findings of 120 patients, 35% had nodules, and 13.3% had ILD (62.5% nonspecific interstitial pneumonia, 25% lymphocytic interstitial pneumonia, 12.5% usual interstitial pneumonia). Bronchiectasis, emphysema, sequelae fibrotic changes, and pleural thickening was found in 3.3%, 5.8%, 15.8%, and 1.7% of patients, respectively. It was observed that there was a significant relationship between the presence of ILD and persistent cough, mediastinal LAP, low DLCO, high ESSDAI and clin-ESSDAI scores reflecting disease activity. DISCUSSION: The most common pulmonary manifestation in our patients was ILD. ILD was observed more frequently in patients with moderate and severe disease activity. Some of the ILD patients were diagnosed while they were asymptomatic. Even if they are asymptomatic, it is important to follow up the patients with physical examination, spirometry, DLCO and thorax CT.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients.

OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.