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.

The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.

Salivary and serum levels of neutrophil proteases in periodontitis and rheumatoid arthritis.

OBJECTIVE: The aim was to profile serum and salivary levels of active-matrix metalloproteinase (aMMP)-8, tissue inhibitor MMP (TIMP)-1, aMMP-8/TIMP-1 ratio, total MMP (tMMP)-9, tMMP-9/TIMP-1 ratio, myeloperoxidase (MPO), and human neutrophil elastase (HNE) in periodontitis and rheumatoid arthritis (RA). MATERIALS AND METHODS: Rheumatoid arthritis patients with periodontitis (RA + P, n = 26), periodontally healthy RA patients (RA, n = 23), systemically healthy periodontitis patients (P, n = 24), and controls (C, n = 24) were included. aMMP-8 levels were determined by a time-resolved immunofluorescence assay (IFMA), TIMP-1, tMMP-9, MPO, and HNE levels were measured by enzyme-linked immunosorbent (ELISA) assays. RESULTS: Higher salivary aMMP-8 (p < 0.001), aMMP-8/TIMP-1 ratio (p = 0.043), tMMP-9 (p = 0.011), tMMP-9/TIMP-1 ratio (p = 0.022), MPO (p = 0.026) and HNE (p < 0.001) levels were detected in P relative to the controls. Salivary TIMP-1 was increased in RA patients regardless of periodontal status (RA + P vs. P: p = 0.038; RA vs. C: p = 0.020). Serum neutrophil proteases were increased in RA groups (RA + P, RA) compared to systemically healthy groups (P, C) (p < 0.05). CONCLUSIONS: Serum levels of neutrophil proteases were increased in RA study groups; however rheumatologic status seemingly does not affect salivary levels of these proteins.

Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: results from a multicenter Psoriatic Arthritis Registry (PsART-ID).

BACKGROUND: This study aimed to assess the mortality of PsA before and during the COVID-19 pandemic. METHODS: From the prospective, multicenter PsART-ID (Psoriatic Arthritis Registry-International Database), patients from Turkey were analyzed by linking the registry to the Turkish Cause of Death Registry. The outcome of interest was death from any cause, pre-pandemic (since the onset of registry-March 2014-March 2020), and during the pandemic (March 2020-May 2021). The crude mortality rate and standardized mortality ratio (SMR) were determined. RESULTS: There were 1216 PsA patients with a follow-up of 7500 patient-years. Overall, 46 deaths (26 males) were observed. In the pre-pandemic period, SMR for PsA vs the general population was 0.95 (0.61-1.49), being higher in males [1.56 (0.92-2.63)] than females [0.62 (0.33-1.17)]. The crude mortality rate in PsA doubled during the pandemic (pre-pandemic crude mortality rate: 5.07 vs 10.76 during the pandemic) with a higher increase in females (2.9 vs 8.72) than males (9.07 vs 14.73). CONCLUSION: The mortality in PsA was found similar to the general population in the pre-pandemic era. The mortality rates in PsA doubled during the pandemic. Whether PsA patients have more risk of mortality than the general population due to COVID-19 needs further studies. Key Points • Decrease in mortality in PsA might be expected with the more effective treatment options and better disease control. • A crude mortality rate is comparable to the general population and not increased until the pandemic. • Currently, there is a 2-fold increase in crude mortality rate possibly due to the COVID-19.

Clinical and laboratory factors associated with bamboo spine in patients with axial spondyloarthritis: are there clues for bamboo spine?

OBJECTIVES: To analyse the clinical and laboratory factors associated with bamboo spine. METHODS: Data of patients fulfilling the 2009 ASAS classification criteria for axial spondyloarthritis, registered in the national, multicentre, longitudinal, and observational database of TReasure was analysed. Radiographs were assessed using the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Data of patients with a bamboo spine (Group 1) was compared to data derived from patients with a longstanding disease of at least 15 years but no syndesmophytes (Group 2). RESULTS: Out of the 5060 patients, 1246 had eligible radiographs. There were 111 patients (8.9%) with a bamboo spine. Male sex was more common among patients with bamboo spine. The median BMI of 27.7 (25.8-31.1) in Group1 was higher than the BMI of 25.9 (22.9-29.2) in Group 2 (p<0.001). Hip arthritis, present or documented by a physician, was more common in Group 1 [(58/108 (53.7%) vs. 35/103 (34%), p=0.004]. There was a tendency towards a more prevalent enthesitis in these patients [29.1% (25/86) vs. 15.9%(11/69), p=0.054]. HLA-B27 status did not differ between groups. Smoking was more prevalent in Group 1. Multivariate logistic regression analysis revealed that male sex, body mass index, hip arthritis, and enthesitis are associated with bamboo spine in axSpA. CONCLUSIONS: Bamboo spine was more common in the male sex and associated with a delay in diagnosis, high BMI, hip involvement, and enthesitis. The constellation of increased body weight, hip arthritis, and enthesitis may imply that mechanical stress contributes to radiographic damage in the presence of chronic inflammation.

Case of MOG-IgG-associated disease with ankylosing spondylitis: A rare coexistence.

Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is an inflammatory neurological disease. It progresses with attacks by affecting the optic nerves and spinal cord. Bilateral or recurrent optic neuritis are the most common findings in adult patients. Its association with systemic autoimmune disorders such as Sjögren syndrome, antiphospholipid syndrome, autoimmune thyroiditis, and celiac disease is rare. The first and only case of MOGAD in a patient with ankylosing spondylitis with a history of anti-tumor necrosis factor-alpha (anti-TNF-α) use was reported. Herein, we present the coexistence of MOGAD in a patient with AS who did not have a history of anti-TNF-α therapy.

Evaluation of the frequency and intensity of COVID-19 in patients with ankylosing spondylitis under anti-TNF therapy.

BACKGROUND: Dear Editor, After the coronavirus disease 2019 (COVID-19) pandemic affected the whole world, rheumatologists began to think about how COVID-19 will progress in patients with inflammatory conditions. High cytokine levels play a role in the pathophysiology of COVID-19 infection. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to have a key role in the pathogenesis of chronic immune-mediated diseases. AntiTNF therapy may cause an increase in active tuberculosis, other granulomatous diseases, and serious infections [1]. According to many studies, rheumatological diseases have not been identified as a risk factor for severe COVID-19 infection [2]. Should significantly increased cytokine levels during COVID-19 infection make us consider anticytokine therapies that may be used in the treatment of patients with COVID-19 a risk? We aimed to explore whether the frequency of COVID-19 infection increased, the effect of comorbidities on the frequency of infection, and whether the severity of the disease and need for intensive care support increased in patients who used anti-TNF agents. We performed a retrospective case-control study between March and December 2020 in Sakarya University Training and Research Hospital. Retrospectively, we evaluated whether there was a difference in the frequency and severity of COVID-19 in our patients diagnosed with ankylosing spondylitis (AS), 77 of whom were using anti-TNF and 49 of whom didn't use anti-TNF. Hospitalization and intensive care unit (ICU) requirements were evaluated as endpoints. In the anti-TNF group, patients used adalimumab, etanercept, certolizumab, infliximab, and golimumab. Patients were questioned at an outpatient clinic in person or by phone. Seventy-seven patients with AS using anti-TNF agents (58 males, 19 females) and 49 patients with AS (38 males, 11 females) not using anti-TNF agents were included in the study (p = 0.943). Mean age of patients using antiTNF agents was 41.53 ± 10.38, and mean age of patients not using anti-TNF agents was 42.94 ± 10.86 (p = 0.468). Thirty-three (42.9%) patients were smokers in the antiTNF group, while 23 (46.9%) patients were smokers in the group not using TNFi (p = 0.791). There was 12 pack-year smoking in the anti-TNF group, and 14 pack-year smoking in not using TNFi (p = 0.623). The frequency of diabetes mellitus (DM), hypertension (HT), amiloidosis, familial mediterranean fever (FMF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) was similar in both groups (p = 0.403, p = 0.999, p = 0.521, p = 0.999, p = 0.999, respectively). Six patients using TNFi and 3 patients not using TNFi recovered from COVID-19 infection. However, this result was not statistically significant (p = 0.999). One patient using anti-TNF was hospitalized but with no need for admission to the ICU (p = 0.999). All 9 patients recovering from COVID-19 were male (p = 0.113). There were 2 (22.2%) smokers in the SARS-CoV-2 positive group and 54 (46.2%) smokers in SARS-CoV-2 negative group (p = 0.297). There was 37.5 pack-year smoking in SARS-CoV-2 positive group, and 12 pack-year smoking in SARS-CoV-2 negative group (p = 0.151). Nobody has comorbidities (DM, HT, amiloidosis, FMF, CAD, COPD) in SARS-CoV-2 positive group. There were patients with DM (5.1%), HT (15.4%), amiloidosis (1.7%), FMF (1.7%), CAD (0.9%) and COPD (0.9%) in SARS-CoV-2 negative group (p = 0.999, p = 0.356, p = 0.999, p = 0.999, p = 0.999, p = 0.999, respectively). Having comorbidities was not detected to be associated with frequency of COVID-19. 31 (40.3%) patients were using adalimumab, 25 (32.5%) patients were using etanercept, 13 patients were using (16.9%) certolizumab, 6 (7.8%) patients were using golimumab, and 2 patients (2.6%) were using infliximab in TNF group. Six patients using anti-TNF (2 adalimumab, 1 etanercept, 1 golimumab,2 infliximab) and 3 nonuser patients recovered from COVID-19 (p = 0.999). No statistically significant difference was found between SARS-CoV-2 positive and negative patients in terms of the types of anti TNF they used. Patients were called in March 2020, and they were advised to terminate their anti-TNF therapy, when the COVID-19 pandemic began. Among those who used antiTNF, 2 (33.3%) people who had COVID-19 and 38 (53.5%) people who did not have COVID-19 interrupted treatment (p = 0.419). Anti-TNF users who did not have COVID-19 stopped taking the treatment for an average of 3 months (min 2-max 4 months) starting from March 2020, and the patients who had COVID-19 (p = 0.102) stopped taking the treatment for 1.5 months (min 1-max 2 months). Duration of interrupting TNFi was not significant for the risk of COVID-19. Comorbidities, older age, and the presence of active disease have been associated with worse outcomes in previous studies [3]. In our study, the anti-TNF using and the nonuser groups were similar according to age, sex, and comorbidities. Although comorbidities in COVID-19 are associated with severe disease in the literature, we did not find a significant difference in our study. This result is probably related to our insufficient number of patients. As a result, we found that the use of anti-TNF did not increase the frequency and severity of COVID-19. In a recently published multicenter study, it was stated that the use of biological DMARDs in patients with inflammatory rheumatic diseases was not significantly associated with a worse outcome of COVID-19. But unlike our study, having no comorbidities was associated with a decreased risk of a worse outcome [4]. There are currently studies investigating the therapeutic utility of infliximab and adalimumab in hospitalized COVID-19 patients [5]. The results of these studies are very important. The usability of TNFi in treatment and at which stage of the disease anti-TNF agents can be used are wondered. We will see the course of the disease all over the world after the administration of the COVID-19 vaccines, but we still need more information about effective and safe treatment. RESULTS: The authors declare that there is no conflict of interest. DISCUSSION: The authors did not receive support from any organization for this work.

Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

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.

Budd-Chiari syndrome in Behçet's disease: a retrospective multicenter study.

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.

The First Effect of COVID-19 Pandemic on Starting Biological Disease Modifying Anti-Rheumatic Drugs: Outcomes from the TReasure Real-Life Database.

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.

In the era of disease-modifying antirheumatic drugs, how close are we to treating rheumatoid arthritis without the use of glucocorticoids?

We wanted to see how close we could get to our goal of treating rheumatoid arthritis (RA) without the use of glucocorticoids (GCs) in the disease-modifying antirheumatic drugs (DMARDs) era using real-life data. Established in 2017, the TReasure database is a web-based, prospective, observational cohort for Turkey. As of May 2019, there were 2,690 RA patients recorded as receiving biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) therapy. At the start of the bDMARDs or tsDMARDs, patients with follow-up visits of at least 3 months were registered. At the time of registration and the last visit, doses of GCs were recorded and it was determined if the target dose of ≤ 7.5 mg was achieved. During registration and follow-up, 23.4% of the patients did not receive GCs and 76.5% of the patients received GCs at any time. GCs could be stopped after 59 (25-116) months in 28.4% of these patients, but 71.6% of patients were still using GC. The target GC dose could not be achieved in 18.2% of these patients (n = 352). The rate of continuing to use GC was significantly higher in women, in the elderly, those with rheumatoid factor (RF) positive, with higher Visual Analog Scale (VAS) pain and Disease Activity Score (DAS)-28. The initial GC dose of ≥ 7.5 mg/day was found to be crucial in not reaching the GC target dose (p < 0.001, OR 39.0 (24.1-63.2)). The initial GC dose of ≥ 7.5 mg/day, female gender, age, RF positivity, high DAS28, and VAS pain level were all highly related for GC continuation. Despite the use of DMARDs, our data revealed that we are still far from achieving our goal of treating RA without using steroids.

Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results.

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.

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

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

Ultrasonographic evaluation of femoral cartilage thickness in patients with familial Mediterranean fever.

OBJECTIVES: This study aims to determine femoral cartilage thickness using ultrasonography in familial Mediterranean fever (FMF). PATIENTS AND METHODS: A total of 45 patients (16 males, 29 females; mean age: 38.5±9.1 years; range, 24 to 49 years) with the diagnosis of FMF and 31 healthy individuals (6 males, 25 females; mean age: 37.0±8.7 years; range, 25 to 47 years) between January 2016 and July 2016 were included in this study. Clinical data and demographic characteristics of the patients were recorded. All FMF cases in the study were in remission with colchicine treatment. The thickness of femoral cartilage in both knees were evaluated using ultrasonography. Three measurements (mid-point) were taken from both knees (at the medial/lateral femoral condyles and intercondylar area). RESULTS: Ultrasonographical measurements revealed that cartilage measurements of FMF patients were significantly thinner at both the medial/lateral femoral condyles and intercondylar area on the right knee and at the medial/lateral femoral condyles on the left knee (p<0.001). The cartilage measurements in FMF patients were significantly thinner at the intercondylar area on left knee, compared to those in controls (p=0.023). CONCLUSION: Our study showed decreased femoral cartilage thickness in FMF patients. These findings indicate that even if these patients do not have an attack, they may have subacute and chronic arthritis in their joints, and their femoral cartilage thickness can be affected.

Disease characteristics of psoriatic arthritis patients may differ according to age at psoriasis onset: cross-sectional data from the Psoriatic Arthritis-International Database.

OBJECTIVES: To explore the impact of early versus late-onset psoriasis (PsO) on the disease characteristics of psoriatic arthritis (PsA) in a large-multicentre cohort. METHODS: The data from a multicentre psoriatic arthritis database was analysed. Patients were grouped according to age at psoriasis onset (early onset; <40 years of age, late-onset; >40 years of age) and disease characteristics of the groups were compared by adjusting for BMI and PsA duration, where necessary. RESULTS: At the time of analyses, 1634 patients were recruited [62.8% females; early onset 1108 (67.8%); late-onset, 526 (32.2%)]. The late-onset group was more over-weight [66.8% vs. 86.8%, p<0.001; adjusted for age - aOR 1.55 (1.11-2.20; 95% CI)]. The early onset group had more scalp psoriasis at onset (56.7% vs. 43.0%, p<0.001), whereas extremity lesions were more common in the late-onset group (63.8% vs. 74.2%, p<0.001). Axial disease in males and psoriatic disease family history in females were significantly higher in the early onset group [38.0% vs. 25.4%; p=0.005; adjusted for PsA duration - aOR 1.76 (1.19-2.62; 95% CI) / 39.5% vs. 30.1%; p=0.003; OR 1.51 (1.15-1.99; 95% CI), respectively]. Psoriatic disease activity parameters, patient-physician reported outcomes and HAQ-DI scores were similar in both groups. CONCLUSIONS: Clinical features of PsA may be affected by the age at onset of PsO. Different genetic backgrounds in early and late-onset PsO may be driving the differences in psoriasis and PsA phenotypes.

Biological and targeted-synthetic disease-modifying anti-rheumatic drugs with concomitant methotrexate or leflunomide in rheumatoid arthritis: real-life TReasure prospective data.

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.

PsART-ID inception cohort: clinical characteristics, treatment choices and outcomes of patients with psoriatic arthritis.

OBJECTIVES: Our aim is to understand clinical characteristics, real-life treatment strategies, outcomes of early PsA patients and determine the differences between the inception and established PsA cohorts. METHODS: PsArt-ID (Psoriatic Arthritis- International Database) is a multicentre registry. From that registry, patients with a diagnosis of PsA up to 6 months were classified as the inception cohort (n==388). Two periods were identified for the established cohort: Patients with PsA diagnosis within 5-10 years (n = 328), ≥10 years (n = 326). Demographic, clinical characteristics, treatment strategies, outcomes were determined for the inception cohort and compared with the established cohorts. RESULTS: The mean (s.d.) age of the inception cohort was 44.7 (13.3) and 167/388 (43.0%) of the patients were male. Polyarticular and mono-oligoarticular presentations were comparable in the inception and established cohorts. Axial involvement rate was higher in the cohort of patients with PsA ≥10 years compared with the inception cohort (34.8% vs 27.7%). As well as dactylitis and nail involvement (P = 0.004, P = 0.001 respectively). Both enthesitis, deformity rates were lower in the inception cohort. Overall, 13% of patients in the inception group had a deformity. MTX was the most commonly prescribed treatment for all cohorts with 10.7% of the early PsA patients were given anti-TNF agents after 16 months. CONCLUSION: The real-life experience in PsA patients showed no significant differences in the disease pattern rates except for the axial involvement. The dactylitis, nail involvement rates had increased significantly after 10 years from the diagnosis and the enthesitis, deformity had an increasing trend over time.

Salivary and serum concentrations of monocyte chemoattractant protein-1, macrophage inhibitory factor, and fractalkine in relation to rheumatoid arthritis and periodontitis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), and fractalkine are chemokines that are expressed by a variety of cell types to regulate macrophage inflammatory response. The aim of the study was to examine the effects of periodontitis and rheumatoid arthritis (RA) on their serum and salivary concentrations. METHODS: Adults with either periodontitis (P, n = 21), or with rheumatoid arthritis (RA, n = 23), or with both diseases (RA+P, n = 23) were included in the study. Systemically and periodontally healthy individuals (n = 22) served as controls. Saliva and serum samples were collected from all participants before the medical and periodontal examinations. Salivary and serum MCP-1, MIF, and fractalkine concentrations were measured by the Luminex technique. Total salivary protein levels were determined by the Bradford assay. RESULTS: Salivary MCP-1, MIF, and fractalkine concentrations were elevated in both RA groups (RA+P and RA) in comparison with systemically healthy controls. As related to total salivary protein levels, higher MCP-1 (P = 0.003) and fractalkine (P = 0.045) concentrations were found in controls compared with the P group. In serum, MCP-1 concentrations in the RA+P group were higher (P = 0.003) than those of group P. Elevated serum fractalkine concentrations were observed in both periodontitis groups (RA+P, P = 0.014; and P, P = 0.013) compared with controls. CONCLUSIONS: In RA, MCP-1, MIF, and fractalkine concentrations are elevated in saliva. These chemokines may disrupt oral macrophage responses and potentially take part in the interaction between periodontitis and RA.

Impact of Having Family History of Psoriasis or Psoriatic Arthritis on Psoriatic Disease.

OBJECTIVE: Psoriatic arthritis (PsA) has a genetic background. Approximately 40% of patients with psoriasis or PsA have a family history of psoriasis or PsA, which may affect disease features. The aim of this study was to assess the effects of family history of psoriasis and PsA on disease phenotypes. METHODS: Data from 1,393 patients recruited in the longitudinal, multicenter Psoriatic Arthritis International Database were analyzed. The effects of family history of psoriasis and/or PsA on characteristics of psoriasis and PsA were investigated using logistic regression. RESULTS: A total of 444 patients (31.9%) had a family history of psoriasis and/or PsA. These patients were more frequently women, had earlier onset of psoriasis, more frequent nail disease, enthesitis, and deformities, and less frequently achieved minimal disease activity. Among 444 patients, 335 only had psoriasis in their family, 74 had PsA, and 35 patients were not certain about having PsA and psoriasis in their family, so they were excluded from further analysis. In the multivariate analysis, family history of psoriasis was associated with younger age at onset of psoriasis (odds ratio [OR] 0.976) and presence of enthesitis (OR 1.931), whereas family history of PsA was associated with lower risk of plaque psoriasis (OR 0.417) and higher risk of deformities (OR 2.557). Family history of PsA versus psoriasis showed increased risk of deformities (OR 2.143) and lower risk of plaque psoriasis (OR 0.324). CONCLUSION: Family history of psoriasis and PsA impacts skin phenotypes, musculoskeletal features, and disease severity. The link between family history of psoriasis/PsA and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets.