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.

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.

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 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.

Association between oxygen delivery and digital ulcers in systemic sclerosis.

OBJECTIVE: Tissue hypoxia due to microvasculopathy is the main cause of digital ulcers (DUs) in systemic sclerosis (SSc). Reduced oxygen delivery (DO2) to the tissues may also contribute to the development of DU. This study was conducted to investigate the association between DO2 and DUs in patients with SSc. METHODS: In all, 111 patients and 30 healthy controls were enrolled. DO2 was calculated by using the formula; DO2 = Cardiac output × arterial oxygen saturation (SpO2) × serum haemoglobin level × 1.39 × 10. Both right index finger SpO2 measurements (index-SpO2) and highest value of SpO2 (maximum SpO2) obtained among the fingers of the subjects were used for the calculations and DO2 results were adjusted both for weight and body surface area (BSA). RESULTS: Mean DO2 was lower in SSc patients as compared to controls in all 4 different calculations but the difference was only statistically significant when using index-SpO2 and adjusting for BSA (498 mL/min/m2 vs 549 mL/min/m2, p = 0.03). There was a strong positive correlation between cardiac output and DO2 calculated by using the index-SpO2 (r = 0.903; p < 0.001). Of the SSc patients, 46 (41.4 %) had DUs within the last 12 months. Patients with DUs had higher mean mRSS, lover mean FVC and more frequently diffuse disease, interstitial lung disease, anti-SCL70 antibody positivity (p < 0.05 for all). No difference was observed in DO2 among DU positive or DU negative groups by any calculation (p > 0.05 for all). CONCLUSIONS: DO2 in SSc patients seems to be lower than healthy controls. However, DO2 is similar between the patients with and without DUs. Our results suggest that the contribution of DO2 is negligible to the development of DU and support the major role of microvasculopathy in SSc patients with DUs.

Differences and similarities of proliferative and non-proliferative forms of biopsy-proven lupus nephritis: Single centre, cross-disciplinary experience.

OBJECTIVE: We aimed to compare clinical features, outcomes, treatments, and to define the predictive factors of complete renal response (CRR) in patients with proliferative and non-proliferative lupus nephritis (LN). METHODS: Patients with systemic lupus erythematosus (SLE) followed between 2014 and 2020 at Hacettepe University Hospitals and who had a kidney biopsy were the subject of the study. One hundered and sixteen patients' kidney biopsies reported as LN were evaluated retrospectively. Clinical characteristics and laboratory values at the time of kidney biopsy, histopathological forms of LN, and renal response (complete or partial) were recorded. We analyzed the association between CRR rates during the 2-year follow-up after induction therapy and the predictive factors for CRR. RESULTS: Of 116 (93 females, 23 males) patients, 95 (81.9%) were in the proliferative group (class III and IV) and 21 (18.1%) were in the non-proliferative group (class II and V). In the proliferative group, the percentage of the patients with elevated basal creatinine levels, median daily proteinuria, anti-double-stranded DNA (dsDNA) positivity, low C3 and C4 levels, the presence of active urinary sediment, and median renal SLE Disease Activity Index (SLEDAI) scores at the time of kidney biopsy were significantly higher than the non-proliferative group. Renal response status during the 2-year follow-up after induction therapy was available for 99 patients. During this time, 70 (70.7%) patients had achieved CRR and time-to-CRR was similar between the proliferative and non-proliferative groups (p = 0.64, log-rank test). The Cox proportional hazards model showed that achievement of CRR was associated with female gender [HR: 2.15 (1.19-3.89 95% CI), p = 0.011], newly diagnosed SLE with renal biopsy [HR: 2.15 (1.26-3.67 95% CI), p = 0.005], hypertension [HR: 0.40 (0.27-0.94 95% CI), p = 0.032], eGFR increase [HR: 1.01 (1.00-1.01 95% CI), p = 0.046], and the presence of active urinary sediment [HR: 0.46 (0.22-0.96 95% CI), p = 0.039]. CONCLUSIONS: Achieving CRR was similar in proliferative and non-proliferative LN patients, although certain laboratory parameters differed at the onset. Our results indicated the importance of kidney biopsy in the decision-making of treatment of SLE patients with renal involvement and that the defined factors associated with CRR achievement help to predict good renal response.

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.

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

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

The frequency of Achilles and plantar calcaneal spurs in gout patients

Background/aim: Gout may cause various radiographic abnormalities such as cartilage loss, spurs, sclerosis, and periostal new bone formation. The purpose of this study was to investigate the frequency of Achilles and plantar spurs and related factors in gout patients. Matherial and methods: We performed a retrospective review of gout patients, treated at Hacettepe University hospitals between 2014 and 2019. We identified patients from the hospital records using the ICD-10 code (M10). Demographic and clinical features, comorbidities, and foot radiographies were collected. The radiographies were evaluated by a rheumatologist (U.K.) who was experienced in musculoskeletal radiography. Factors predicting the spurs were analyzed by logistic regression analysis. Results: 181 patients who had lateral foot radiograph were included in this study. Eighty-one (44.7%) patients had score ≥ 2 Achilles spur, 81 (44.7%) patients had score ≥ 2 plantar spur, and 22 (12.1%) patients had no spur. Age, disease duration, duration between the gout diagnosis and appearing spur, the presence of metabolic comorbidities and hypertension were higher in both Achilles and plantar spurs than no spur group. Forty (22.1%) patients had score ≥ 2 both Achilles and plantar spur. In this group, the mean age was older and the proportion of metabolic comorbidities was higher than the groups of Achilles and plantar spur with a score 0 or 1. Predictor of the development of large or moderate-severe calcaneal spur was the existence of metabolic comorbidity [OR (95% CI): 3.49 (1.11­11.0) and p = 0.033]. Conclusion: The presence of metabolic comorbidities increases the frequency of calcaneal spurs in gout patients. This condition can be explained by the impaired microvascular structure and increased hypoxia resulting in calcification on the tendon and ligament insertion sites.

Investigation of Intestinal Protozoon Prevalence in Immunocompromised Patients at a University Hospital

Objective: Immunocompromised patients are at a greater risk of developing intestinal parasite infections. In this study, we examined the presence of Enterocytozoon bieneusi, Encaphalitozoon intestinalis and other intestinal protozoa in stool samples of immunosuppressed patients. Methods: A total of 100 stool samples were obtained from patients receiving chemotherapy because of solid organ tumour with haematological malignancies and those receiving immunosuppressive treatment because of rheumatic diseases, organ transplant patients and patients receiving treatment for HIV-related infections. Stool samples were examined by using the native-lugol method in which the stool concentration, modified Kinyoun acid-fast and trichrome staining methods and parasite presence were analysed. The stool samples were also examined for the presence of Enterocytozoon bieneusi and Encephalitozoon intestinalis using an indirect fluorescent antibody method. Results: Intestinal parasites were detected in 12% of all patients. The distribution of intestinal parasites in patients were 7% Blastocystis spp., 2% Blastocystis spp. + Dientamoeba fragilis, 1% Blastocystis spp. + Entamoeba coli, 1% Blastocystis spp. + Giardia intestinalis and 1% G. intestinalis. Microsporidia spp. were detected in 4% of all patients by the IFAT method and in 8% of all patients by calcoflour staining method. Conclusion: In our study, the most prevalent parasite detected in the immunosuppressed patients was Blastocystis spp. The pathogenesis of Blastocystis spp. remains to be controversial, and their role in immunocompromised patients continues to remain unknown. Although these rates detected in our study are similar to the prevalence in the normal population, it is important to study these microorganisms in immunocompromised patients in terms of the associated decreasing morbidity and mortality rates.

Preferences of inflammatory arthritis patients for biological disease-modifying antirheumatic drugs in the first 100 days of the COVID-19 pandemic

Background/aim: To evaluate treatment adherence and predictors of drug discontinuation among patients with inflammatory arthritis receiving bDMARDs within the first 100 days after the announcement of the COVID-19 pandemic. Materials and methods: A total of 1871 patients recorded in TReasure registry for whom advanced therapy was prescribed for rheumatoid arthritis (RA) or spondyloarthritis (SpA) within the 3 months (6­9 months for rituximab) before the declaration of COVID-19 pandemic were evaluated, and 1394 (74.5%) responded to the phone survey. Patients' data regarding demographic, clinical characteristics and disease activity before the pandemic were recorded. The patients were inquired about the diagnosis of COVID-19, the rate of continuation on bDMARDs, the reasons for treatment discontinuation, if any, and the current general disease activity (visual analog scale, [VAS]). Results: A total of 1394 patients (493 RA [47.3% on anti-TNF] patients and 901 SpA [90.0% on anti-TNF] patients) were included in the study. Overall, 2.8% of the patients had symptoms suggesting COVID-19, and 2 (0.15%) patients had PCR-confirmed COVID-19. Overall, 18.1% of all patients (13.8% of the RA and 20.5% of the SpA; p = 0.003) discontinued their bDMARDs. In the SpA group, the patients who discontinued bDMARDs were younger (40 [21­73] vs. 44 years [20­79]; p = 0.005) and had higher general disease activity; however, no difference was relevant for RA patients. Conclusion: Although the COVID-19 was quite uncommon in the first 100 days of the pandemic, nearly one-fifth of the patients discontinued bDMARDs within this period. The long-term effects of the pandemic should be monitored.

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

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

Evaluating skeletal muscle mass with ultrasound in patients with systemic sclerosis.

OBJECTIVES: Patients with systemic sclerosis (SSc) have an increased risk for loss of skeletal muscle mass. Ultrasonography (US) is a safe and promising method to evaluate muscle mass. In this study, we aimed to assess the frequency and clinical associations of low muscle mass status in patients with SSc, investigate the correlations between muscle mass sonographically measured regional muscle thicknesses (MTs), and explore the utility of US in predicting low muscle mass. METHODS: A total of 93 patients with SSc (86 women) were included in the study. Appendicular skeletal muscle mass (ASM) was calculated using a bioelectric impedance analysis and adjusted for height2 (ASM index, ASMI). Low muscle mass was defined as an ASMI of <7.26 kg/m2 for men and <5.50 kg/m2 for women. MT of the gastrocnemius medialis (GM), rectus femoris (RF), rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TA) muscles were assessed by US. Correlations between ASMI and individual MTs were evaluated. Receiver operating characteristic analysis was used to determine the optimal cutoff values of MTs in predicting low muscle mass. RESULTS: Low muscle mass was present in 13.9% of patients. Diffuse disease subset (53.8% vs 17.5%), antitopoisomerase-1 antibody positivity (76.9% vs 47.5%), and malnutrition (61.5% vs 8.8%) were more frequent in patients with low muscle mass (P < 0.05 for all). MTs of RA (0.54 vs 0.75 cm), TA (0.30 vs 0.34 cm), and GM (1.23 vs 1.51 cm) muscles were significantly lower in patients with low muscle mass (P < 0.05 for all). RA (r = 0.322; P = 0.002), external oblique (r = 0.310; P = 0.002), TA (r = 0.205; P = 0.049), and GM (r = 0.513; P < 0.001) MTs were positively correlated with ASMI. Selected cutoff values for GM and RA MTs showed the highest sensitivity (92.3% for both) and negative predictive value (97.9% and 97.6%, respectively) in predicting low muscle mass status (area under the curve: 0.846 and 0.760, respectively) in the receiver operating characteristic analysis. CONCLUSIONS: Low muscle mass is prevalent in SSc and patients with diffuse disease are at particular risk for this condition. US measurement of abdominal and calf MTs may be used as a screening method to detect low muscle mass due to its high sensitivity and negative predictive value.

Pregnancy outcomes in partners of male ankylosing spondylitis patients treated with anti-tumour necrosis factor-α biologics: real-life results from a single-centre cross-sectional study.

Most patients with inflammatory arthritis are at their reproductive ages. Use of anti-tumour necrosis factor alpha (anti-TNF-α) agents, one of the important treatment options for inflammatory arthritis, can cause foetal morbidity and mortality. While most studies on the effects of anti-TNF-α agents on pregnancy outcomes are about maternal exposure, the number of studies on the risks related to paternal exposure is insufficient. This study aimed to assess pregnancy periods and outcomes of the partners of male ankylosing spondylitis (AS) patients receiving anti-TNF-α treatment during the preconception period. Totally, 163 male AS patients using anti-TNF-α agents were identified from the Hacettepe University Biological Registry. Of these patients, 45 (27.6%) who declared that their partners got pregnant after initiation on anti-TNF-α agents were included. Data regarding demographics and drug exposure and pregnancy and infant outcomes were evaluated. Of 45 pregnancies, 39 (86.7%) resulted in healthy live births, 3 (6.7%) resulted in spontaneous abortion, and 3 (6.7%) were terminated with curettage. Of 39 live births, 34 (87.2%) were term and 5 (12.8%) were preterm, 30 (76.9%) had normal birth weight, 6 (15.4%) had low birth weight, and 3 (7.7%) had fetal macrosomia. No congenital malformations related to paternal exposure were observed. This study is valuable as being one of the studies providing pregnancy outcomes of partners of male AS patients receiving anti-TNF-α agents with its relatively high number of patients. The results suggested that paternal exposure to anti-TNF-α agents during preconception period could be safe on pregnancy outcomes.

Anti-interleukin-6 (tocilizumab) therapy in Takayasu's arteritis: a real life experience.

BACKGROUND: Tumour necrosis factor inhibitors and anti-interleukin-6 (anti-IL-6) therapies are increasingly being used in Takayasu's arteritis (TA) patients who are unresponsive to corticosteroids ± conventional immunosuppressive agents. The aim of this study is to assess the efficacy and safety of anti-IL-6 (tocilizumab) therapy in refractory TA patients in real life. METHODS: Fifteen TA patients (86.7% were female) who received at least 3 cycles of tocilizumab therapy were retrospectively assessed by clinical, laboratory, and radiological evaluations before and after tocilizumab therapy. RESULTS: The median (min-max) age of the patients at evaluation was 35 (20-58) years and the median disease duration from diagnosis was 24 (12-168) months. The median (min.-max.) duration of follow-up after tocilizumab was 15 (3-42) months. There was a significant decrease in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and patient global visual analogue scale (VAS) scores of patients after tocilizumab therapy. The median (min.-max.) ESR was 26 (5-119) vs. 3 (2-49) mm/h, P = 0.02; CRP was 39.8 (2.4-149.0) vs. 7.9 (0-92.9) mg/L, P = 0.017; and patient global VAS was 50 (0-90) vs. 30 (0-60), P = 0.027, respectively. In 8 patients, ESR and CRP levels were in the normal range in the last control. Imaging modality results after tocilizumab were available for 9 patients; 8 patients were radiologically stable and regression was seen in 1 patient. Comparable imaging modality results before and after tocilizumab were available for 5 patients; 4 patients were radiologically stable and regression was seen in 1 patient. Radiological findings were consistent with laboratory responses. Glucocorticoid dosages decreased from a mean dosage of 16.2 (9.1) mg/day at baseline to 7.1 (3.8) mg/day (P = 0.001) at the last follow-up visit. There was no increase in the steroid dosage in any of the patients. All patients tolerated tocilizumab well. DISCUSSION: Based on retrospective real life data, anti-IL-6 (tocilizumab) appears to be an effective and tolerable treatment option in refractory TA patients.

The investigation of Strongyloides stercoralis seroprevalence in immunosupressed patients in Turkey

Background/aim: In immunosuppressed patients, strongyloidiasis can be lifethreatening because of hyperinfection or dissemination. Therefore, diagnosis of S. stercoralis is important in immunosuppressed patients with chronic strongyloidiasis. In this study, our objective was to investigate the presence of S. stercoralis antibodies by an ELISA method in immunosuppressed patients. Materials and methods: A total of 100 immunosuppressed patients' sera were included in the study. Forty-two of the patients were receiving immunosuppressive therapies for cancer or being treated for hematopoietic malignancies, 38 of the patients were receiving immunosuppressive drugs for rheumatic diseases, 14 were receiving immunosuppressive therapies for liver transplantation. Two of the patients were being treated for HIV infection and 4 were being treated for hypogammaglobulinemia. As control group, 50 individuals without a known disease were included in the study. The presence of IgG antibodies against S. stercoralis was investigated with a commercial ELISA kit. Results: S. stercoralis antibody test was positive in 4 of 100 (4%) sera from immunosuppressed patients. All control patients were negative for S. stercoralis. Conclusions: Strongyloidiasis can be a lifelong chronic infection if not treated. In patients who are going to receive immunosuppressive therapy, it should be tested before treatment, as it can become a disseminated and life-threatening infectious disease.

Methodology of a new inflammatory arthritis registry: TReasure

Background/aim: The TReasure registry, created in 2017, is an observational multicenter cohort that includes inflammatory arthritis patients. This article reviews the methodology and objectives of the TReasure registry established to collect data from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Methodology: Fifteen rheumatology centers in Turkey will contribute data to the TReasure database. The actual proprietor of the database is the Hacettepe Rheumatology Association (HRD) and Hacettepe Financial Enterprises. Pharmaceutical companies that operate in Turkey (in alphabetical or er), Abbvie, Amgen, BMS, Celltrion Healthcare, Novartis, Pfizer, Roche, and UCB, support the TReasure registry. TReasure is a web-based database to which users connect through a URL (https://www.trials-network.org/treasure) with their unique identifier and passwords provided for data entry and access. TReasure records demographic and clinical features, comorbidities, radiology and laboratory results, measures of disease activity, and treatment data. Discussion: TReasure will provide us with various types of data, such as a cross-sectional view of the current nationwide status of the patients currently receiving these treatments, and retrospective data as much as allowed by the participating centers' records. Finally, a high-quality prospective dataset will be built over the ensuing years from patients with a new diagnosis of RA or SpA.

Alteration of the microRNA expression profile in familial Mediterranean fever patients.

OBJECTIVES: Phenotypic heterogeneity in familial Mediterranean fever (FMF) disease indicated that FMF is not a simple monogenic disease. Therefore it has been suggested that epigenetic factors can be one of the reason for the variations. We undertook this study to test potential involvement of miRNAs in the pathogenesis of FMF. METHODS: miRNA array was performed on whole blood RNA samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-). The raw data was analysed by Multi Experiment Viewer (MeV) and candidate miRNAs were determined according to fold change (more than 2.0 or less than -2.0). The validation of differentially expressed miRNAs was done by qRT-PCR. Then we performed pathway analyses with using bioinformatics tools. RESULTS: 14 miRNAs were found to be significant among groups through the analysis with MeV. miR-20a-5p, miR-197-3p, let-7d-3p and miR-574-3p were found to be associated with inflammatory pathway related genes according to DAVID analysis. MiR-20a-5p (FDR: 0,00, FCH: 5.55) was significantly up regulated whereas miR-197-3p (FDR: 0,00, FCH: -2.27) was down regulated in homozygotes patients. Both let-7d-3p (FDR: 0.00, FCH: 28.75) and miR-574-3p (FDR: 0.00, FCH: 3.95) were up regulated in heterozygote patients group. CONCLUSIONS: We showed that there are several differentially expressed miRNAs both in homozygote and heterozygote FMF patients compared to controls and healthy carriers. Thus we suggest that these miRNAs, related with inflammatory pathways may be responsible for the expression of the disease in FMF.

The clinical features and outcomes of Turkish patients with IgG4-related disease:a single-center experience

Background/aim: Since the majority of the IgG4-related disease (IgG4-RD) patients in the literature are from the Far East and the United States, there is a lack of large series from other parts of the world. We aimed to identify the clinical characteristics and outcome of Turkish IgG4-RD patients from a tertiary center. Materials and methods: Fifty-two patients classified as having definite IgG4-RD according to comprehensive diagnostic criteria were included in the study. Patients not fulfilling the definite criteria due to lack of pathologic specimen and/or serum IgG4 levels were excluded (n = 47). Clinical, laboratory, and histopathological features and treatment approaches were analyzed. Results: Median age at diagnosis was 51.1 years and sex predominance was not observed (male/female: 26/26). Median follow-up duration was 18 (IQR 25­75: 8­35) months. Retroperitoneal fibrosis was the most frequent presentation. Twenty-four (46.1%) patients had localized involvement. Corticosteroids were the mainstay of treatment (92.5%). Rituximab had been used for cases resistant to previous treatment or with relapses in 19 (47.5%) patients. A complete response was achieved in 52.5% and partial response (<50% regression) in 40%. Conclusion: This large and first cohort of IgG4-RD patients from Turkey showed similar clinical features to European cohorts, except for the male predominance in previous cohorts. Corticosteroids and rituximab are effective in IgG4-RD but there is still uncertainty about the usage of corticosteroid-sparing agents.