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.

Assessing the accuracy and completeness of artificial intelligence language models in providing information on methotrexate use.

We aimed to assess Large Language Models (LLMs)-ChatGPT 3.5-4, BARD, and Bing-in their accuracy and completeness when answering Methotrexate (MTX) related questions for treating rheumatoid arthritis. We employed 23 questions from an earlier study related to MTX concerns. These questions were entered into the LLMs, and the responses generated by each model were evaluated by two reviewers using Likert scales to assess accuracy and completeness. The GPT models achieved a 100% correct answer rate, while BARD and Bing scored 73.91%. In terms of accuracy of the outputs (completely correct responses), GPT-4 achieved a score of 100%, GPT 3.5 secured 86.96%, and BARD and Bing each scored 60.87%. BARD produced 17.39% incorrect responses and 8.7% non-responses, while Bing recorded 13.04% incorrect and 13.04% non-responses. The ChatGPT models produced significantly more accurate responses than Bing for the "mechanism of action" category, and GPT-4 model showed significantly higher accuracy than BARD in the "side effects" category. There were no statistically significant differences among the models for the "lifestyle" category. GPT-4 achieved a comprehensive output of 100%, followed by GPT-3.5 at 86.96%, BARD at 60.86%, and Bing at 0%. In the "mechanism of action" category, both ChatGPT models and BARD produced significantly more comprehensive outputs than Bing. For the "side effects" and "lifestyle" categories, the ChatGPT models showed significantly higher completeness than Bing. The GPT models, particularly GPT 4, demonstrated superior performance in providing accurate and comprehensive patient information about MTX use. However, the study also identified inaccuracies and shortcomings in the generated responses.

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.

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.

Clinical features of Behçet's disease and prediction of the use of biologics in 488 cases: a single tertiary center study.

The objectives are to describe the demographic and clinical properties of Behçet's disease (BD) and investigate their relationship with the use of biological agents. Four hundred-eighty-eight patients, (299 (61.3%) males, 189 (38.7%) females), who fulfilled the ISG classification criteria for BD were included, retrospectively. The patient's demographics, disease onset age (DOA), clinical findings of the disease, and the drugs were determined and analyzed statistically. The means of patient age and DOA were 40.7 ± 9.9 and 30.8 ± 8.8 years, respectively. The most common initial findings were oral ulcer (OU)s (30.1%), genital ulcer (GU) (27.5%), ocular involvement (OI) (12.5%), and papulopustular lesion (PPL)s (10.1%). The most common clinical manifestations were OUs (96.9%), PPLs (70.2%), HLA-B51 (64.4%), positive pathergy reaction (26.4%), GU (58.8%), OI (44.7%), erythema nodosum (29.8%), and vascular involvement (VSI) (27.3%). Although, the frequency of GU was higher in females (p = 0.01), PPLs (p = 0.001) and VSI (p = 0.001) were higher in males. Sixty-three (8.9%) patients used a biological agent. Its frequency was higher in younger patients (< 40 years) (p = 0.006), males (p = 0.012) and patients with OI (p = 0.001). Besides, the DOA (p = 0.012) and the current age (p = 0.001) were lower in biological agent users. The possibility of using biological agent was increased in males (OR = 2.2), patients with OI (OR = 2.7) and young patients (OR = 0.9). Mucocutaneous lesions are distinctive features of BD, especially OUs precede other findings. GU was more common in females and PPLs and VSI were in males. The probability of using biologics is higher in males, patients with OI, and young patients.

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.

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.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1ß, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10(-12)), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10(-13)). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10(-15)), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10(-8)). Serum IL-1ß, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1ß and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1ß function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

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.

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.

Isotretinoin-induced sacroiliitis in patients with hidradenitis suppurativa: a case-based review.

Hidradenitis suppurativa (HS) is a chronic, suppurative skin disease characterized by painful nodules, particularly in the axillae and groin. Isotretinoin can be used in the treatment of HS; however, it may paradoxically lead to skin lesions or worsen the existing lesions. Isotretinoin, which is commonly used in the treatment of severe acne, is associated with several side effects, including rheumatic side effects and rarely sacroiliitis. In this study, we discussed two cases who presented with low back pain after isotretinoin was used for the treatment of acne vulgaris. The patients did not have low back pain before isotretinoin use and did not have enthesitis, dactylitis, uveitis, psoriasis, recent infection, trauma, and family history spondylitis. HLA-B27 was negative. Bone-marrow edema was detected at the sacroiliac joint on magnetic resonance imaging. Because of these findings, sacroiliitis related to the drug was considered in our patients and isotretinoin treatments were discontinued. Because the patients' low back pain continued when they administered non-steroidal anti-inflammatory drugs, biological drug treatments were started. Both cases presented had a simultaneous HS lesion. After the treatment, both low back pain and HS lesions regressed. Patients with isotretinoin therapy should be alerted for inflammatory low back pain and HS lesions that may develop. We should note that biologic agents should be considered in the treatment of resistant cases.

The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia

Background/aim: The distribution of Mediterranean fever (MEFV) gene mutations in Turkish familial Mediterranean fever (FMF) patients varies according to geographic area of Turkey. There is a need for highly representative data for Turkish FMF patients. The aim of our study was to investigate the distribution of the common MEFV mutations in Turkish FMF patients in a nationwide, multicenter study. Materials and methods: Data of the 2246 FMF patients, from 15 adult rheumatology clinics located in different parts of the country, were evaluated retrospectively. The following mutations have been tested in all patients: M694V, M680I, M694I, V726A, and E148Q. Results: There were 1719 FMF patients with available genetic testing. According to the genotyping, homozygous M694V, present in 413 patients (24%), was the most common mutation . One hundred and fifty-four (9%) of patients had no detectable mutations. Allele frequencies of common mutations were: M694V (n = 1529, 44.5%), M680I (n = 423, 12.3%), V726A (n = 315, 9.2%), E148Q (n = 214, 1%), and M694I (n = 12, <1%). Conclusion: In this large-scale multicenter study, we provided information about the frequencies of common MEFV gene mutations obtained from adult Turkish FMF patients. Nearly half of the patients were carrying at least one M694V mutations in their alleles.

Methodology of a new inflammatory arthritis registry: TReasure

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

Prolonged Tpeak-Tend interval in anti-Ro52 antibody-positive connective tissue diseases.

Patients with connective tissue diseases (CTDs) may have prolonged corrected QT interval which indicates increased risk for ventricular arrhythmias. However, a more sensitive measure of ventricular repolarization, T-peak-to-end (Tpe) interval, has not been studied in CTDs. We aimed to investigate the relationship between ventricular repolarization abnormalities and anti-Ro52-positivity in subjects with connective tissue diseases (CTDs). We enrolled patients with anti-Ro52-positive CTDs, ANA-positive CTDs, and healthy subjects in this cross-sectional study. We excluded conditions potentially affecting the QT interval. We compared the ECG measures between the groups and performed analyses to define factors associated with ventricular repolarization measures. 15 ANA and anti-Ro52-positive, 39 ANA-positive and anti-Ro52-negative, and 22 healthy subjects were enrolled. None of the subjects had rhythm or conduction disturbances. Corrected QT intervals were similar between the groups. Tpe (84, 77.3, and 69.4 msn, respectively) and QT-dispersion (40, 27.2, and 20.1 msn, respectively) were higher in anti-Ro52-positive subjects compared with the ANA-positive and healthy subjects. Anti-Ro52 titers were correlated with Tpe and QT-dispersion (r = 0.52 and p < 0.001 for each). ANA and anti-Ro52-positivity were independently associated with higher Tpe (OR = 7.7, p = 0.001 and OR = 6.9, p = 0.001, respectively), corrected Tpe (OR = 11.3, p = 0.001 and OR = 8.4, p = 0.003, respectively), QT dispersion (OR = 7, p = 0.008 and OR = 13, p < 0.001, respectively), and QTc dispersion (OR = 9.1, p = 0.001 and OR = 14.1, p < 0.001, respectively). This study provides evidence that ANA positivity, especially when concomitant anti-Ro52-positivity is present, significantly deteriorates ventricular repolarization. The aforementioned ventricular repolarization abnormalities may render these subjects susceptible to serious rhythm or conduction disorders in the setting of predisposing conditions.

Investigation of the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis.

Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.

The IL-33 gene is related to increased susceptibility to systemic sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc.

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study.

OBJECTIVE: The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS: Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS: There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION: In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

The process from symptom onset to rheumatology clinic in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is an inflammatory disease of individuals aged over 50 years. Because of the concomitant malignancy possibility and the high prevalence of constitutional symptoms seen in this condition, patients with classical clinical picture often experience delay in diagnosis and treatment and are exposed to a wide list of laboratory and imaging procedures. In this study, we aimed to explore the adventure these patients experience from symptom onset to rheumatology clinic. A total of 106 PMR patients (84 women, 22 men) mean age 70.1 ± 8 were analyzed retrospectively. The time period from the onset of symptoms and referral to rheumatology specialists was explored. Diagnostic methods applied to these patients, antibiotic use and hospitalization during this period were recorded. The interval between the onset of the symptoms and admission to rheumatology unit was 13 ± 13 months. In this period, abdominal computed tomography (29.2 %), chest computed tomography (21.7 %), cranial magnetic resonance imaging (18.9 %) and whole-body scintigraphy (3.8 %) were applied to the patients. About 30 % of the patients were hospitalized for a mean period of 7 ± 3 days before referral to rheumatology unit, and 30 % of the patients were given antibiotics. In order to reduce the delay in the diagnosis of PMR and prevent unnecessary and expensive diagnostic methods, education of clinicians about the diagnosis of PMR may be beneficial.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies with brucellosis.

Anti-cyclic citrullinated peptide (anti-CCP) was positive in 11.5 % and rheumatoid factor was positive in 8.8 % of the patients with Brucella. After a comparative evaluation, we have found out that there was not a statistical significance concerning the anti-CCP levels between the patients with brucellosis and healthy control.