Assessing safety and efficacy of TNFi treatment in late onset ankylosing spondylitis: a TURKBIO registry study.

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.

Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

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.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease?

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.

Is the use of secukinumab after anti-TNF therapy greater than expected for the risk of developing inflammatory bowel disease? / El uso de secukinumab tras la terapia anti-TNF es mayor de lo esperado por el riesgo de desarrollar enfermedad inflamatoria intestinal?

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.(AU)

Objetivo: En este estudio, nuestro objetivo fue presentar datos de la vida real sobre la incidencia de la enfermedad inflamatoria intestinal (EII) entre los pacientes que reciben tratamiento con secukinumab. Métodos: El estudio consistió en 209 pacientes que habían tenido una exposición previa al factor de necrosis antitumoral (TNF) o eran biológicamente naive. Los pacientes con antecedentes preexistentes de EII fueron excluidos del estudio. Resultados: De los 209 pacientes del estudio, 176 (84,3%) tenían espondilitis anquilosante, mientras que 33 (15,7%) tenían artritis psoriásica. 112 (53,6%) pacientes tenían exposición previa a al menos un tratamiento anti-TNF antes de iniciar secukinumab. La EII se desarrolló en 10 (4,8%) de los 209 pacientes. La incidencia de EII entre los pacientes que iniciaron secukinumab como primer agente biológico fue del 1%. Para los pacientes que habían recibido previamente algún tratamiento anti-TNF y posteriormente hicieron la transición a secukinumab, la incidencia de EII fue del 8% (p=0,018, odds ratio (OR): 8,38, IC del 95%: 1,04-67,45). Una media de 3,67 meses (±4,3) después del uso de anti-TNF, mientras que los síntomas de la EII se desarrollaron en el paciente biológicamente naive después de 15 meses. Conclusión: Nuestro estudio observó una incidencia de EII en el 4,8% de los pacientes que usaban secukinumab. Los pacientes que iniciaron secukinumab después de un tratamiento anti-TNF previo mostraron una tasa y un riesgo significativamente mayores de desarrollar EII. El inicio de la EII ocurrió antes en estos pacientes (media de 3,67 meses), mientras que un solo caso de EII mostró una duración más prolongada (15 meses). Se justifican más estudios con un mayor número de pacientes para proporcionar una comprensión más completa de nuestros hallazgos.(AU)

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

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

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

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.

Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

OBJECTIVES: To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). METHODS: The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. RESULTS: Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). CONCLUSIONS: Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

Epidemiological characteristics of hepatitis B and C in patients with inflammatory arthritis: Implications from treasure database.

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.

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

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

The impact of smoking on response to tumor necrosis factor-α inhibitor treatment in patients with ankylosing spondylitis.

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.

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

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

Effects of acute aerobic exercise on brain-derived neurotrophic factor level in rheumatoid arthritis patients.

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.

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

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

Effects of acute aerobic exercise on cytokines, klotho, irisin, and vascular endothelial growth factor responses in rheumatoid arthritis patients.

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-1ß (IL-1ß), 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, IL1ß, 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 IL1ß, 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.

Body mass index does not affect response of rituximab in patients with rheumatoid arthritis: results from the TURKBIO registry.

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/m2 were classified as obese, and patients with a BMI <30 kg/m2 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/m2. 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.

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

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

Prognostic nutritional index as a novel marker for diabetic retinopathy in individuals with type 2 diabetes mellitus.

PURPOSE: In recent years, the prognostic nutritional index (PNI), an easily obtainable nutritional inflammatory marker, has been introduced as an independent prognostic indicator for various types of cancers and cardiovascular diseases. However, its clinical importance in the area of ophthalmology is not well known yet. We aimed to elucidate the association between the PNI and the occurrence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, the PNI was applied to 128 consecutive patients with T2DM. The relationship between the PNI and the occurrence of DR was examined. PNI was calculated as 10× (serum albumin) + 0.005 × (total lymphocyte count). The risk factors for DR were evaluated using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve analysis of PNI for predicting DR was performed. RESULTS: Patients with DR had significantly lower levels of PNI than those without DR (41.20 ± 4.81 and 44.49 ± 3.10, respectively,P< 0.001). Multivariate regression analysis indicated that PNI, together with the duration of diabetes and creatinine, was an independent factor for DR occurrence (odds ratio, 0.885; 95% confidence interval: 0.735-0.971;P= 0.017). ROC curve analysis revealed that the best cutoff value of PNI was 43 (area under the curve: 0.713; sensitivity: 74%; specificity: 64%). CONCLUSION: A lower PNI value is common among T2DM patients with DR and is strongly associated with the occurrence of DR. The PNI might be a useful biomarker for identifying DR to improve the risk stratification and management of T2DM patients.

Serum netrin-1 and netrin receptor levels in fibromyalgia and osteoarthritis.

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 Firat 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.

A real-life analysis of patients with rheumatologic diseases on biological treatments: Data from TURKBIO Registry.

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.