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OBJECTIVE: Systemic lupus erythematosus (SLE) patients have increased risk of coronary heart disease (CHD) that cannot be fully explained by the traditional risk factors. Metabolic alterations like oxidative stress and insulin resistance may be additional risk factors to contribute early and accelerated atherosclerosis in SLE. Our aim was to evaluate malondialdehyde (MDA) level, oxidative stress indicator, and homeostasis model assessment of insulin resistance (HOMA-IR), and possible relationship between oxidative stress and insulin resistance, in SLE. METHODS: This cross-sectional controlled study included 30 SLE patients (SLE group) and 15 age- and sex-matched healthy controls (HC group). The SLE patients were classified into subgroups based on the disease activity index as active or inactive. Serum MDA, insulin, C-peptide, fasting blood glucose, lipid profile, acute phase reactants, tumor necrosis factor (TNF)-a, interleukin (IL)-6 and HOMA-IR were determined. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U and Pearson tests. RESULTS: In the SLE group, TNF-a (7.9 [0.5-57.8] vs. 3.9 [0.3-6.3] pg/ml, p<0.01), IL-6 (9.2 [0.1-33.9] vs. 2.2 [0.1-4.8] pg/ml, p<0.01), MDA (2.3 [0.1-6.7] vs. 0.95 [0.5-2.96] nmol/ml, p<0.01) and C-peptide (1.9 [0.9-3.5] vs. 1.5 [1.1-2.4] ng/ml, p<0.01) levels were higher than in the HC group, while HOMA-IR index (1.7 [0.5-6.5] vs. 1.2 [0.8-2.9], p>0.05) was nonsignificantly higher. In the SLE group, MDA levels were correlated with insulin (r=0.614, p<0.05) and HOMA-IR (r=0.601, p<0.05). CONCLUSION: In inflammatory diseases, relations between oxidative stress and insulin resistance, each of them triggers or enhances the other one, come to an impasse. In conclusion, this modifiable impasse might be important to prevent the development of atherosclerosis in SLE. [ABSTRACT FROM AUTHOR]

Objectives: Inflammatory low back pain (IBP) is a typical feature of spondylarthritis (SpA). IBP can be caused by infections, drugs, and different malignancies. Among cancers, hematologic malignancies and solid tumors can cause IBD either paraneoplastically or through metastasis. In this study, we aimed to present the demographic and clinical characteristics of our patients who presented with IBP in the last 10 years and whose final diagnosis was malignancy., Methods: Thirty-four patients who presented with inflammatory low back pain in the last 10 years and were diagnosed with malignancy as the final diagnosis were included in the study. Thirty-six patients, diagnosed as axial SpA, with similar age-sex ratio of 1:1 from each center were included as the control group., Results: Hematologic malignancies were multiple myeloma, acute leukemia, and lymphoma in descending order. Solid tumors were breast cancer, lung cancer, bone tumors, prostate, colon, embryonal carcinoma, and malignancy of unknown primary. In malignancy-related low back pain, the hematologic/solid ratio was similar (18/16), the interval between symptom and diagnosis was shorter, and biomarkers' results such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum lactate dehydrogenase (LDH) levels were significantly higher than the control group., Conclusion: Malignancy-related low back pain differs from SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. Malignancies must be kept in mind in the differential diagnosis, and in order to validate our findings, the results of larger case series are needed, especially in terms of causative malignancies. Key Points • In malignancy-related inflammatory low back pain, the hematologic/solid ratio was similar, the interval between symptom and diagnosis was shorter, and acute phase reactant levels and LDH levels were significantly higher. • Malignancy-related inflammatory low back pain differs from axial SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. • Malignancies must be kept in mind in the differential diagnosis of axial SpA., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Clinical data on the use of tumour necrosis factor inhibitors (TNFi) in late-onset ankylosing spondylitis (LoAS) are limited. The present study aimed to evaluate efficacy, safety, and treatment adherence associated with the initial use of TNFi therapy in biologic naive patients diagnosed with LoAS. Patients whose age of onset was ≥ 45 years and < 45 years were classified as having LoAS and YoAS, respectively, based on the age of symptom onset. There were 2573 patients with YoAS and 281 LoAS. Baseline disease activity measures were similar between the groups. No significant differences were seen between the two groups in response to treatment and in remaining on the first TNFi at 6, 12 and 24 months. In the LoAS group, the analysis showed that TNFi discontinuation was linked to VAS pain score (HR 1.04; 95% CI 1.01-1.06). Patient groups had similar rates of adverse events (YoAS: 8.7% vs. LoAS: 11.7%). In both biologic naive LoAS and YoAS patients, the study showed that the initial TNFi therapy was equally effective and safe., (© 2024. The Author(s).)

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., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept., Objective: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population., Methods: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi., Results: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97)., Conclusion: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design., Competing Interests: Competing interests: RA has nothing to disclose. DM has nothing to disclose. SAB reports grants from Pfizer outside of this work and speaker fees from Benecke. DC has nothing to disclose. CC reports reports personal fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer outside the submitted work. DDC has nothing to disclose. LD reports contract with BMS outside the present work. OE reports consulting and speaker fees from AbbVie, Pfizer, Eli Lilly, Novartis and Jansen. DH has nothing to disclose. KLH reports grant support from Pfizer and Bristol Myers Squibb and speaking fees from AbbVie. FI reports consulting fees from AbbVie, Janssen, UCB, Galapagos and speaker fees from AbbVie, Galapagos, Eli Lilly, Pfizer and UCB. NI reports consulting and speaking fees from AbbVie, Novartis, UCB, Eli Lilly, Pfizer and Celltrion. LKF has nothing to disclose. SSK has nothing to disclose. TKK reports grants from AbbVie, BMS, Galapagos, Novartis, Pfizer and UCB, consulting fees from AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB Grünenthal, Sandoz and speaker fees from Grünenthal, Sandoz. BFL reports consulting fees from Eli Lilly, Pfizer and AbbVie, and speaking fees from Sandoz. GL has nothing to disclose. DN reports grants from MSD, consulting fees from BMS, Lilly, Novartis, Pfizer, UCB and speaker fees from Pfizer and UCB. KP reports speaker fees from Novartis, Eli Lilly, Roche, Pfizer, Sobi, AbbVie, Pfizer and MSD. MPS has nothing to disclose. AR reports grants from Amgen, AstraZeneca, Novartis, AbbVie, Pfizer, MSD, Lilly, Boehringer Ingelheim, speaker fees from Amgen, AbbVie and Novartis. ZR reports consulting fees from AbbVie, Pfizer, Janssen, AstraZeneca, Novartis, Boehringer Ingelheim, Eli Lilly and speaker fees from AbbVie, Pfizer, Janssen, AstraZeneca, Novartis, Boehringer Ingelheim, Eli Lilly, SOBI, Lek (Sandoz). AS reports speaker fees from AbbVie, BMC, MSD, Pfizer and Roche. PV reports grants from Pfizer and Galapagos, consulting fees from Galapagos, Gilead, Pfizer, Sidekick Health, speaking fees from Eli Lilly, Galapagos and Roularta. RW has nothing to disclose. JZ reports speaking fees from AbbVie, Sobi, Pfizer and Eli Lilly. DSC reports consulting fees from Medela AG. AF reports grants from AbbVie, Pfizer, Galapagos and Eli Lilly, consulting fees from Eli Lilly, Pfizer, AbbVie, speaker fees from Pfizer, Eli Lilly, AbbVie, MSD and BMS. KL has received consultancy and/or speaker fees from Pfizer, Viatris, Celltrion and Galapagos paid to her institution., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: In this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment., Methods: The study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study., Results: Of the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04-67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months., Conclusion: Our study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

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.

Background/aim: The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19., Materials and Methods: In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews., Results: The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively., Conclusion: This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases., (© TÜBİTAK.)

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., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

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., Competing Interests: A.Y. has received project grant from Roche Pharmaceuticals, Turkey. C.S.B. and T.Y.C. are employees of Pfizer Pharmaceuticals, Istanbul, Turkey. S.A. is an employee and shareholder of Pfizer Inc., Istanbul, Turkey. N.I., K.Y.A., M.A.O., A.T., H.K., I.S., G.C., Y.E., Y.P., H.E.D., T.O., A.C., A.S.S., S.A., E.D.-E., S.S.K., R.P.-S., S.Y., S.G., O.S.-G., and F.O. declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The current study aimed to examine the psychiatric symptoms that can be seen in fibromyalgia (FM) patients, their attitudes toward seeking psychological help, and their concerns about stigma. Besides, it was investigated whether the stigma concerns that they may experience about receiving psychiatric treatment constitute an obstacle for patients to receive psychiatric treatment., Subjects and Methods: This cross-sectional descriptive study was conducted between February and July 2020. Various seeking help were measured with Attitude Towards Seeking Psychological Help Scale-Short Form (ATSPPH-SF), Self-Stigma in the Process of Seeking Psychological Help Scale (SSPSPHS), Intention to Seek Psychological Help Inventory (ISPHI), and Social Stigma Due to Seeking Psychological Help Scale (SSDSPHS). FM symptoms of patients were measured with The Symptom Screening Questionnaire, Revised 90 Items (SCL-90-R). Quality-of-life parameters were measured with Fibromyalgia Impact Questionnaire (FIQ)., Results: Fibromyalgia patients had higher somatization (p=0.001), psychotism (p=0.045) and phobic anxiety (p=0.015) scores than controls. The ATSPPH-SF (p=0.002) and SSPSPHS (p=0.043) scale scores of the FM patients were higher than the controls. There was a significant positive correlation between FIQ and SSPSPHS (r=0.288, p=0.043) and SCL-90 overall (r=0.602, p<0.001) and all subscales scores. Patients with high active psychotic symptom levels had higher FM exposure scale scores and SCL-90 overall scores than those with low active psychotic symptom levels (p<0.001)., Conclusions: The findings of this study showed that fibromyalgia patients have more somatization symptoms than healthy individuals, and as psychiatric symptoms increase in these individuals, their level of being affected by FM increases.

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.

Background: To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-α inhibitor (TNFi)., Methods: AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline., Results: There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1- Q3: 1.3-3.8), and disease duration was 3.5 years (Q1-Q3: 0.7-8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4-5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1-5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6-3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1-2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2-2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses., Discussion: This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate.

Background/aim: Adipose tissue produces several inflammatory mediators. Thus, obesity affects the disease course and the responses to the antirheumatic agents in inflammatory diseases. The aim of the study was to determine whether the body mass index (BMI) is involved in the response to rituximab in rheumatoid arthritis (RA)., Materials and Methods: This multicenter retrospective study included 206 RA patients who received rituximab from the Turkish Biologic (TURKBIO) registry between 2011 and the end of May 2017. Demographic and clinical data including age, sex, disease type, disease duration, and previous or current treatment with disease-modifying antirheumatic drugs (DMARDs) and biological drug durations are stored in the database. Patients with a BMI ≥30 kg/m 2 were classified as obese, and patients with a BMI <30 kg/m 2 were classified as nonobese. Kaplan-Meier survival analysis was performed to estimate the drug survival. The subgroups were compared using the log-rank test., Results: The mean BMI of 206 patients included in the study was 27.05 (17.2-43.4) kg/m 2 . There were 59 (28.6%) patients in the obese group and 147 (71.4%) patients in the nonobese group. The mean age, female percentage, and baseline disease activity score 28 (DAS28) were higher in the obese group than in the nonobese group. However, the ΔDAS28 at both 6 and 12 months were not significantly different between the groups (p = 0.785 and p = 0.512, respectively). Patient pain Visual Analogue Scale (VAS), patient fatigue VAS, and patient global VAS scores were also significantly higher at baseline in the obese group (p = 0.003, p = 0.006, and p = 0.006, respectively). However, no significant difference was found in terms of changes in patient pain VAS, patient fatigue VAS, patient global VAS and physician global VAS scores at 6 and 12 months compared to those at baseline. Rituximab treatment was ongoing for 71.2% of the obese and 63.3% of the nonobese patients (p = 0.279). The median drug survival duration was 77 months in the obese group and 62 months in the nonobese group (p = 0.053). The estimated drug survival rates for rituximab were not statistically significantly different in the obese and nonobese groups. Rituximab-related side effects were also similar between the groups., Conclusion: In obese and nonobese patients with RA, rituximab treatment exhibits similar side effects and similar long-term efficacy. These results suggest that obesity does not alter drug survival for rituximab and response rates, in RA and rituximab may be a favorable treatment agent in patients with RA and obesity., (© TÜBİTAK.)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that causes cartilage and bone damage as well as disability.  AIMS : The aim of this study was to examine the effects of acute aerobic exercise on cytokines such as serum interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α) and irisin, vascular endothelial growth factor(VEGF) and klotho in RA patients.  METHODS: Forty RA patient and 40 healthy volunteers of the same age participated in this study. All participants walked on the treadmill for 30 minutes at 60-80% of maximal heart rate. Blood samples were taken before and immediately after the exercise. Serum levels of IL-6, IL1β, TNF-α and irisin, VEGF and klotho were measured by enzyme-linked immunosorbent analysis.  RESULTS: Baseline levels of inflammatory cytokines, irisin, VEGF and klotho were found to be higher in RA patients compared to the control group. In both groups, there was an increase in serum klotho levels after exercise compared to baseline (p<0.05), while a decrease in IL1β, TNF-α levels were observed. While serum VEGF level decreased in RA group, it increased in the control group(p<0.05). Irisin levels decreased in both groups. IL-6 level did not change in the control group, while it increased in RA group. A single exercise session had an acute anti-inflammatory effect in RA patients., Conclusion: It can be concluded that acute aerobic exercise can be beneficial for patients with RA through cytokine, irisin, klotho and VEGF levels, and also it can be safely implemented to the RA rehabilitation program for additional anti-inflammatory effects. Trial registration ClinicalTrials.gov: NCT04439682., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

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., (© 2022. The Author(s).)

Objectives: This study aimed to evaluate the hepatitis B (HBV) and C (HCV) frequency and clinical characteristics among patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who receive biological treatments., Patients and Methods: The observational study was conducted with patients from the TReasure database, a web-based prospective observational registry collecting data from 17 centers across Türkiye, between December 2017 and June 2021. From this database, 3,147 RA patients (2,502 males, 645 females; median age 56 years; range, 44 to 64 years) and 6,071 SpA patients (2,709 males, 3,362 females; median age 43 years; range, 36 to 52 years) were analyzed in terms of viral hepatitis, patient characteristics, and treatments used., Results: The screening rate for HBV was 97% in RA and 94.2% in SpA patients. Hepatitis B surface antigen (HBsAg) positivity rates were 2.6% and 2%, hepatitis B surface antibody positivity rates were 32.3% and 34%, hepatitis B core antibody positivity rates were 20.3% and 12.5%, HBV DNA (deoxyribonucleic acid) positivity rates were 3.5% and 12.5%, and antibody against HCV positivity rates were 0.8% and 0.3% in RA and SpA patients, respectively. The HBsAg-positive patients were older and had more comorbidities, including hypertension, diabetes, and coronary artery disease. In addition, rheumatoid factor (RF) positivity was more common in HBsAg-positive cases. The most frequently prescribed biologic disease-modifying antirheumatic drugs were adalimumab (28.5%), etanercept (27%), tofacitinib (23.4%), and tocilizumab (21.5%) in the RA group and adalimumab (48.1%), etanercept (31.4%), infliximab (22.6%), and certolizumab (21.1%) in the SpA group. Hepatitis B reactivation was observed in one RA patient during treatment, who received rituximab and prophylaxis with tenofovir., Conclusion: The epidemiological characteristics of patients with rheumatic diseases and viral hepatitis are essential for effective patient management. This study provided the most recent epidemiological characteristics from the prospective TReasure database, one of the comprehensive registries in rheumatology practice., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

Objectives: The study aimed to investigate the variation of brain-derived neurotrophic factor (BDNF) levels following acute exercise in patients with rheumatoid arthritis (RA)., Patients and Methods: This cross-sectional study was conducted with 88 participants (25 males, 63 females; mean age: 45.1±8.3 years; range, 18 to 65 years) between July 2020 and May 2021. Of the participants, 44 were RA patients, and 44 were age-and sex-matched healthy controls. Aerobic exercise was utilized in all participants for a single session. Depression and anxiety levels were evaluated with the Beck Depression Inventory and Hospital Anxiety and Depression Scale. Blood samples were collected from all subjects before and immediately after the intervention., Results: Serum BDNF levels (both baseline and after exercise) were similar in the RA and control groups. Although serum BDNF levels significantly decreased in both groups after aerobic exercise (Wilcoxon rank p<0.05), ΔBDNF levels were significantly higher in the RA group than in the control group (p=0.047). Additionally, ΔBDNF levels were significantly correlated with the Hospital Anxiety and Depression Scale scores in the RA group (p<0.05) but not in the control group., Conclusion: A single bout of exercise may effectively decrease serum BDNF levels in patients with RA and healthy subjects. The long-term effect of exercise on BDNF levels should be investigated in prospective studies., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The coronavirus disease 2019 pandemic has been resulting in increased hospital occupancy rates. Rheumatic patients cannot still reach to hospitals, or they hesitate about going to a hospital even they are able to reach. We aimed to show the effect of the first wave of coronavirus disease 2019 pandemic on the treatment of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or spondyloarthritis., Methods: Patients were divided into three groups as follows: pre-pandemic (Pre-p: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within 6 months before March 11, 2020); post-pandemic A (Post-p A: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the first 6 months after March 11, 2020); post-pandemic B (Post-p B: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the second 6 months)., Results: The number of rheumatoid arthritis patients in the Post-p A and B groups decreased by 51% and 48%, respectively, as compared to the Pre-p group similar rates of reduction were also determined in the number of spondyloarthritis patients. The rates of tofacitinib and abatacept use increased in rheumatoid arthritis patients in Post-p period., Conclusion: The number of rheumatoid arthritis and spondyloarthritis patients starting on biological disease-modifying anti-rheumatic drugs for the first time decreased during the first year of the coronavirus disease 2019 pandemic.

Objective: We aimed to evaluate quality of life (QoL), disease activity, compliance to treatment, patient and physician preferences for route of administration (RoA), status of health and pain in RA patients starting advanced treatments or needing a switch, and the factors associated with patient preferences., Methods: A multicentre, prospective, observational and 1-year follow-up study was conducted, between 2015 and 2020, in adult RA patients using advanced treatments for the first time or needing a switch in their current treatments. All the data collected were entered into electronic case report forms. DAS in 28 joints with ESR [DAS28-4(ESR)], EuroQol 5-Dimensional Questionnaire (EQ-5D), HAQ Disability Index (HAQ-DI), Compliance Questionnaire for Rheumatology (CQR-19), Work Productivity and Activity Impairment Instrument (WPAI) and Patient Global Assessment-Visual Analogue Scale (PGA-VAS) questionnaires were used for longitudinal assessments., Results: Four hundred and fifty-nine patients were enrolled. Three hundred and eight patients (67.1%) attended the final study visit at 12 months and were included for comparative analyses. Irrespective of RoA, the disease activity and QoL improved significantly at 12 months, whereas compliance worsened. At baseline and 12 months, EQ-5D and DAS28-4(ESR) scores were significantly correlated ( P  < 0.001). The WPAI scores changed significantly in favour of better outcomes over 12 months after initiation of advanced treatment or switching ( P  < 0.001). A higher proportion of patients preferred an oral RoA, in comparison to physicians (53.6% vs 31.4%; P  < 0.001). Patient and physician RoA preferences were independent of gender, age, disease duration, advanced treatment type and the EQ-5D-3L, DAS28-4(ESR), HAQ-DI, PGA-VAS and CQR-19 scores at baseline., Conclusion: The oral route was more frequently preferred by patients compared with physicians, although patients' preference rates showed a slight increase towards the end of the treatment, which might be an important factor for RA outcomes. Better control of disease activity and QoL were achieved at 12 months, regardless of RoA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Achilles tendinopathy can be noticed in both acromegaly and ankylosing spondylitis (AS). Acromegaly patients presenting with tendinopathy findings may be confused with AS findings. In this study, sonoelastrographic findings of Achilles tendon are explored in patients with AS and acromegaly., Methods: 25 patients with AS, 30 patients with acromegaly, and 18 healthy controls were enrolled in the study. Achilles tendon was evaluated by sonoelastography in all the study participants., Results: The thickness of Achilles tendon in neutral positions was higher in acromegaly patients than those in AS patients. The sonoelastography measurement of Achilles tendon was increased in acromegaly patients when compared to the control group and AS patients., Conclusion: The thickness of Achilles tendon can increase in patients with acromegaly and AS. However, the sonoelastographic features of Achilles tendon can be similar in patients with AS and acromegaly.

Objective: The aim of this study is to examine the changes in physical activity level, fatigue, depression, and sleep quality in patients with Behçet's disease during the COVID-19 pandemic., Methods: The study was designed as an online questionnaire applied to individuals who are being followed up with the diagnosis of Behçet's disease in the rheumatology department. Data were collected using multiple scales including International Physical Activity Questionnaire (IPAQ), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Pittsburg Sleep Quality Index (PSQI), and Visual Analogue Scale (VAS) to evaluate physical activity level, fatigue, depression, sleep quality, and pain, respectively., Results: Sixteen patients diagnosed with Behçet's disease were included in the study. No statistically significant difference was observed between the IPAQ, FSS, BDI, PSQI, and VAS assessment scores before COVID-19 and during COVID-19 period (P > .05 for all)., Conclusion: Thinking of the negative effects of aggressive clinical symptoms, Behçet's disease patients should be supported in physical activity and psychosocial status.

Objectives: This study aims to define serum levels of netrin-1 and netrin receptors in patients with fibromyalgia (FM) and osteoarthritis (OA)., Patients and Methods: This cross-sectional study was conducted with a total of 150 female participants (mean age: 47.2±16.1 years; range, 18 to 89 years) at Fırat University between June 2016 and December 2016. The participants were evaluated in three groups: the FM group with 50 patients, the OA group with 50 patients, and the control group, which included 50 healthy volunteers. Netrin-1, netrin receptors (DCC, UNC5B, and UNC5D), interleukin (IL)-6, IL-10, and IL-17 levels were analyzed by the enzyme-linked immunosorbent assay from the serum samples of the participants., Results: The level of serum netrin-1 was significantly lower in the FM group than in the control and OA groups (p<0.01 and p<0.001, respectively). However, the difference between patients with OA and healthy controls in terms of netrin-1 was not statistically significant (p>0.05). In addition, serum levels of netrin receptors and cytokines in the FM group were similar to the control group (p>0.05). However, serum DCC, UNC5D, IL-6, and IL-10 levels were higher in the OA group compared to the control group (p<0.001, p<0.05, p<0.01, and p<0.001, respectively)., Conclusion: Serum netrin-1 level is suppressed in FM, which suggests that netrin-1 is influential in FM pathogenesis., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish Society of Physical Medicine and Rehabilitation.)

Objective: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018., Methods: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens., Results: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31., Conclusion: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is important in the process of inflammation and fibrosis. The adenosine 5'-monophosphate-activated protein kinase (AMPK) enzyme can affect JAK/STAT pathway. Tofacitinib is a pan-JAK inhibitör. Metformin activates AMPK enzyme. We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-β cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc). 40 Balb/c female mice were divided into 4 groups: (control, sham (BLM), tofacitinib and metformin). The mice in the tofacitinib group received oral tofacitinib (20 mg/kg/daily) and mice in the metformin group received oral metformin (50 mg/kg/day) for 28 days. At the end of 4th week, all groups of mice were decapitated and tissue samples were taken for analysis. Histopathological analysis of skin tissue was performed, and mRNA expressions of collagen 3A, IL-17 and TGF-β were assessed by real-time PCR and ELISA. Repeated BLM injections had induced dermal fibrosis. Moreover, the tissue levels of collagen 3A, IL-17 and TGF-β were elevated in the BLM group. Tofacitinib and metformin mitigated dermal fibrosis. They reduced dermal thickness and tissue collagen 3A, IL-17 and TGF-β levels. Tofacitinib and metformin demonstrated anti-inflammatory and anti-fibrotic effects in the mouse model of SSc., (© 2022. The Author(s).)

Objective: The knowledge of physicians about complementary and alternative medicine (CAM) applications is limited. However, especially in chronic diseases, patients and their relatives can often refer to CAM applications. Rheumatic diseases are chronic in nature presenting with a wide clinical spectrum. Despite developing treatment options, achieving treatment goals may not always be possible. For this reason, patients seek different treatment and use traditional and complementary medicine. The aim of this study was to investigate causes, consequences, and the frequency of applying to CAM in rheumatic diseases., Methods: Ninety-five patients admitted to the rheumatology outpatient clinic were enrolled in the study. Health assessment questionnaire and short-form-36 were used to determine the quality of life of patients. Anxiety and depression symptoms were screened by the Hospital Anxiety and Depression scale, a questionnaire that was filled-in by the patients themselves. Also, patients were questioned about their place of residence, level of education, diagnosis, CAM modality types, application reasons, and outcomes. Chi-square test was used to analyze categorical data. Parametric data were analyzed using Student t-test, and nonparametric data were analyzed using Mann-Whitney U test., Results: Thirty-two of our patients had applied to CAM modalities (phytotherapy [34.45%], cupping therapy [21.8%], acupuncture [12.5%], hirudotherapy [12.5%], food supplement [12.5%], and ozone treatment [6.25%]). Only 31.3% of the patients informed their doctors about CAM applications. 47.8% of fibromyalgia patients and 29.2% of patients with inflammatory rheumatic diseases had applied to CAM. Gender, working status, income level, smoking, and alcohol habits were not associated with the application to CAM. However, none of the residents of the village, 14.3% of the residents of the district center, and 41.1% of the residents of the city center had applied to CAM modality. The rate of applying to CAM was 18.2% for those who cannot read and write. The application ratio of CAM is over 40% among secondary school, high school, and university graduates., Conclusion: Among patients with rheumatic diseases, application to CAM is quite common. Very few patients inform their physicians about applying to CAM. Contrary to what is presumed, the rate of applying CAM applications is lower among those living in rural areas and with low education levels.

Objective: To compare the clinical features, laboratory findings, and prognosis of Behçet's disease (BD) patients with and without Budd-Chiari syndrome (BCS)., Methods: This multicenter retrospective study investigated 61 (M/F: 41/20) patients with BD, having coexistent BCS, and 169 (M/F:100/69) BD patients as the control group without BCS from 22 different centers of Turkey diagnosed between 1990 and 2017., Results: Of the total 61 BD patients with BCS, the onset of the first symptom and the median age of diagnosis were earlier in contrast to BD patients without BCS (p = 0.005 and p = 0.007). Lower extremity deep vein and inferior vena cava (IVC) thrombosis were more common in patients with BCS (all; p < 0.01) compared to the control group. Mortality was significantly higher in BD-BCS patients with IVC thrombosis than in the controls (p = 0.004). Since most of the cases in our cohort had chronic and silent form of BCS, mortality rate was 14.8%, which was on the lower range of mortality rate reported in literature (14-47%). While all BD-BCS patients received immunosuppressive (IS) agents, only half of them received additional anticoagulant treatments. Among IS agents, interferon treatment was more frequently used in this cohort (19%), compared to other series reported in literature (2.3%)., Conclusion: To our knowledge, this is the largest series of BD patients with BCS. Our patients had earlier disease onset and diagnosis, higher frequency of IVC thrombosis, and higher mortality rate, compared to BD patients without BCS. Mortality was significantly higher in BD-BCS patients with IVC thrombosis compared to controls. Key Points • Mortality rate is higher in BD-associated BCS patients with IVC involvement. • Chronic and silent form of BD-associated BCS has a better prognosis. • The main treatment options are corticosteroids and immunosuppressive agents, whereas anticoagulant treatment remains controversial., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objectives: To understand change in work productivity, activity impairment, quality of life (QoL), and disease activity in patients with psoriatic arthritis (PsA) receiving anti-tumor necrosis factor (anti-TNF) treatment., Method: One hundred twenty patients with PsA receiving anti-TNF therapy were recruited to this noninterventional, observational study. Work disability was assessed via the Work Productivity and Activity Impairment (WPAI) questionnaire and disease activity was calculated via the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) and Disease Activity Index for Psoriatic Arthritis with 28 joints (DAPSA28) score. Patient-reported outcomes (PROs), from visual analog scores and Health Assessment Questionnaire-Disability Index scores, were evaluated to understand the clinical effectiveness at baseline and every 3 months until the month-9 final visit. The American College of Rheumatology (ACR)20/50/70 response criteria were assessed at month 9., Results: A total of 120 patients (females, n = 73) were enrolled in the study. Mean (SD) age and disease duration were 41.6 ± 11.1 years and 6.9 ± 6.5 years, respectively. The most commonly used TNFα inhibitor was adalimumab (42.4%), followed by etanercept (25.8%). All WPAI questionnaire parameters were reduced at the follow-up visits compared with baseline (p < 0.001 for all). PROs and disease activity indicators (DAS28-CRP and DAPSA28) significantly improved during the course of anti-TNF treatments (p < 0.001 for all). Additionally, ACR20/50/70 responses were determined as 86.8%, 63.7%, and 41.8% of patients at the month-9 visit., Conclusions: The real-world data in PsA patients receiving anti-TNF treatment showed improvement in WPAI, QoL, and disease activity over 9 months of treatment., Trial Registration: NCT02028169 Key Points • Psoriatic arthritis (PsA), with debilitating effects on quality of life, occurs mostly in young adults and has negative impacts on employment status and work productivity. • Early PsA diagnosis and treat-to-target treatment strategies aim to reduce pain and joint damage, as well as improve work productivity. • Real-world data on the impact of treatment with anti-tumor necrosis factor (anti-TNF) agents on work productivity in PsA in the literature is scarce. • Our study of real-world data in patients with PsA receiving anti-TNF treatment showed improvement in work productivity, as well as in clinical and patient-reported outcomes., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objective: Rheumatoid arthritis (RA) is a disabling inflammatory disorder. Ginger is used for food and medicine to treat arthralgia, sprains, and muscle aches. Anti-inflammatory effects of ginger have been observed. The aim of our study was to detect the effects of ginger on experimentally induced inflammatory arthritis., Methods: Female Wistar albino rats (n = 21) were randomly separated into three groups (control, arthritis, and arthritis + ginger). Arthritis was generated by an appropriate method using type 2 collagen and Freund's adjuvant (collagen-induced arthritis model). The ginger group was treated starting at the first collagen injection with ginger root extract for 32 days by oral gavage (50 mg/kg/daily). Interleukin (IL)-6, IL-17, tumor necrosis factor-α (TNF-α), sclerostin, dickkopf-related protein-1 (DKK-1), and obestatin serum levels were studied by enzyme-linked immunosorbent assay method. Tissue TNF-α, IL-17, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) levels were detected using the Western blot method., Results: Mean arthritis score and serum levels of TNF-α, IL-6, and IL-17 were significantly decreased in ginger group than in the arthritis group. Increased sclerostin serum level and decreased DKK-1 serum levels were detected in ginger group compared with arthritis group. The decreases of IL-17, TNF-α, COX-2, and NF-κB tissue levels were statistically significant in the ginger group compared with arthritis group. Histopathological evaluation of the ginger group showed a decrease in the inflammation score compared to arthritis group., Conclusion: It can be concluded that ginger has protective properties in the development of inflammatory arthritis. The antiarthritic acts of ginger are related to NF-κB activity and Wnt pathway. Thus, it may be suggested that ginger is a candidate to research in human RA treatment.

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings., Materials and Methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA., Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1β and TNF-α were increased, while dasatinib suppressed their productions from FLSs., Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

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 (6–9 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 [21–73] vs. 44 years [20–79]; 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., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aim: Sjögren’s syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/β-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS., Materials and Methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically., Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group., Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/β-catenin pathway activities may be altered in case of glandular inflammation., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Purpose: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients., Design: Retrospective cohort study., Methods: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded., Results: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both)., Conclusion: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine the real-life efficacy, safety, and drug-retention rates of leflunomide (LEF) or methotrexate (MTX) as a synthetic DMARD used in combination with biological DMARDs for rheumatoid arthritis (RA)., Methods: The TReasure database is a web-based, prospective, observational cohort of RA and spondyloarthritis patients from 17 centres in different regions of Turkey and data entry was enabled since December 2017. Until May 2019, 2556 RA patients on biologic treatment were recorded. Demographic and RA-related data of 1526 patient either received LEF or MTX were compared, efficacy of both drugs compared by RA-disease activity composite indices. Reasons fordrug discontinuation also recorded. Drug retention rates were compared with Kaplan-Meier curves (log-rank test)., Results: Of 2556 RA patients 1526 (59.7%) were receiving concomitant LEF (n=646, 42.3%; median follow up 35 months) or concomitant MTX (n=880, 57.3%; median follow-up 32 months) at the time of initiation to their first bDMARDs. The LEF group were older and had longer disease duration, proportion of females and seropositive patients was higher in this group. In the LEF group, non-anti-TNF agents were used in higher rate. Remission rates, changes in composite indices and rate of comorbidities and adverse events were similar in both groups. The retention rate of LEF + non-anti-TNF b/tsDMARDs was higher compared to MTX + anti-TNF bDMARDs (p=0.002, log-rank). Rates of adverse events were similar in both groups., Conclusions: LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 μL phosphate-buffered saline (PBS), while the mice in other groups received 100 μL (100 μg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses., Objective: In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs., Methods: Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome., Results: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive., Conclusions: Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome., Competing Interests: KT has served as a speaker for Gilead. GH has received grant/research support from Celgene and has served as a speaker for AbbVie, Celgene, Novartis, and UCB Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Esatoglu, Tascilar, Babaoğlu, Bes, Yurttas, Akar, Pehlivan, Akleylek, Tecer, Seyahi, Yuce-Inel, Alpay-Kanitez, Bodakci, Tekgoz, Colak, Bolek, Koca, Kalyoncu, Icacan, Ugurlu, Oz, Hamuryudan, Hatemi and the Turkish Society for Rheumatology COVID-19 Registry Investigators.)

Objectives: This study aims to evaluate the effects of ocrelizumab (OCZ) on familial Mediterranean fever (FMF) attacks in multiple sclerosis (MS) patients with FMF (MS+FMF patients)., Patients and Methods: This retrospective observational study included 11 patients (2 males, 9 females; mean age 46.6±9.2; range, 22 to 55 years) with MS+FMF hospitalized between January 2016 and July 2019. Demographic, clinical, and laboratory parameters and patient reported outcomes were analyzed in patients treated with OCZ for 18 months., Results: Combining OCZ with colchicine in MS+FMF patients significantly reduced the frequency of FMF attacks (p=0.003) and the frequency of joint attacks (p=0.002). Consistent with the clinical improvement, the maximum serum C-reactive protein levels were significantly decreased after combination therapy compared to before combination therapy (p=0.003). MS+FMF patients reported that FMF disease activity improved after OCZ therapy (Visual Analog Scale [VAS] 74±9.6 vs. VAS 46.5±8.1 mm, p=0.003)., Conclusion: Ocrelizumab therapy led to a prominent decrease in the frequency of FMF attacks, alleviated functional impairment, and improved quality of life in MS+FMF patients., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021, Turkish League Against Rheumatism.)

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis., Materials and Methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund’s adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed., Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws., Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis., Competing Interests: The authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: Secukinumab, a new treatment agent, selectively neutralizes interleukin (IL)-17A. It is used in the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. It is known that the agents used in the treatment of rheumatic diseases have effects on hematological parameters. In this study, we aimed to determine whether hematological parameters are affected in secukinumab therapy in patients with AS and PsA., Methods: Thirty-six patients on secukinumab treatment were included in the study by scanning the database of our hospital. Data on patients' age, gender, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), uric acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine values, and additional drug treatments were recorded from our database. The 0- and 6-month values of patients were analyzed., Results: Sixteen males (44.4%) and 20 females (55.6%) were included in our study. The average age was calculated to be 39.8±8.9 years. Of these, 30 patients receiving secukinumab treatment were diagnosed with AS, and 6 patients were diagnosed with PsA. Twenty-three patients (63.9%) were continued with secukinumab treatment at the 6th month. When CBC, glucose, urea, creatine, AST, ALT, ESR, CRP, and uric acid values of the patients at 0 and 6 months were compared, there was no significant difference., Conclusion: In our study, no significant difference was found between 0 and 6 months in terms of CBC, AST, ALT, urea, creatinine, uric acid, glucose, CRP, and ESR levels in patients receiving secukinumab. However, an increase in hemoglobin values was observed in patients who continued the treatment. These results may suggest that secukinumab treatment has no negative effects on hematological parameters.

Objectives: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe., Methods: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients., Results: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients., Conclusion: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Platelet (PLT) indices are predictive in many diseases and conditions. The relationships of these indices with proteinuria and progression of renal disease are not well known. This study aimed to assess PLT indices in patients with primary glomerular nephrotic range proteinuria (PGNRP), with and without chronic kidney disease (CKD), and to compare these indices with those of healthy individuals (His)., Methods: This cross-sectional study was performed from January 2015 to May 2015. HIs (n = 57) and patients with PGNRP (n = 41) were enrolled. PLT indices and blood biochemistry parameters were compared between HIs and patients with PGNRP, as well as between subgroups of patients with PGNRP who had CKD (n = 23) and those who did not have CKD (n = 18)., Results: There were no statistically significant differences in any PLT indices (i.e., platelet number, mean platelet volume, plateletcrit, and platelet distribution width) between HIs and patients with PGNRP, or between the subgroups of patients with PGNRP. However, patients with PGNRP who had CKD exhibited higher median C-reactive protein and mean albumin levels, compared with patients who did not have CKD., Conclusions: Pathological processes in proteinuria and CKD are not associated with PLT indices.