A rare disease with many faces: A multicenter registry of IgG4-related disease in children.

OBJECTIVES: We aimed to report the characteristics of pediatric IgG4-related disease (IgG4-RD) through a multicentre registry, to assess disease clusters, and to evaluate the performances of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria in this cohort. METHODS: Data of IgG4-RD patients in 13 pediatric rheumatology centers were recorded to a web-based registration system. The diagnosis of IgG4-RD was made according to the 2011 comprehensive diagnostic criteria. RESULTS: Thirty-five children (19 females and 16 males) with IgG4-RD were enrolled. The median age at diagnosis was 13.3 (25p-75p; 9.9-15.2) years. The most common organ involvement was the eye (n = 21, 60%), followed by lymph nodes (n = 12, 34.3%), musculoskeletal system (n = 12, 34.3%), and neurological system (n = 9, 25.7%). We identified three clusters in our study cohort: those with eye involvement (n = 11, 31.4%), those with eye involvement and neurological findings (n = 15, 42.9%), and those with pancreato-hepatobiliary disease and lymph node involvement (n = 9, 25.7%). Serum IgG4 levels were high in 19 out of 28 patients (67.8%). All patients except one received corticosteroid treatment, and azathioprine was the most preferred drug as a steroid-sparing agent. The sensitivities of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were 5.7% and 88.5%, respectively. CONCLUSION: IgG4-RD has a wide variety of clinical manifestations, however in children the most common presentation was orbital involvement. The 2020 RCD criteria had a better performance whereas the 2019 ACR/EULAR classification criteria performed poorly in pediatric patients.

A Canadian vasculitis patient-driven survey to highlight which prednisone-related side effects matter the most.

OBJECTIVES: Although management of vasculitis has evolved over the last decades, glucocorticoids (GC) have remained the cornerstone of treatment. The side effects (SE) of GC are well known by the clinicians; their importance for patients with vasculitis has not been investigated as extensively as in other rheumatological conditions. METHODS: An online questionnaire surveyed between April 29th. to July 31st, 2022 with Vasculitis Foundation Canada about the patient experience and SE of prednisone. The survey included 5 questions about prednisone dose and duration, 21 about specific SE (with a rating of 1-10, and one question each on worst prednisone, and worst vasculitis, SE), and four other questions about knowledge and perception of possible alternatives to prednisone (namely, avacopan). RESULTS: A total of 97 patients (53 GPA/MPA, 44 other vasculitides) completed the survey. Their mean duration of GC use was 62.7±83.7 months, and 49.5% of patients were still on GC (daily dose, 8.4±6.2mg). All the patients reported ≥1 GC-related SE, and 67.0% reported ≥11/19 pre-specified SE of interest. Among ranked SEs, acne was the lowest score, whereas moon face/torso hump had the highest score, just above weight gain, insomnia and decreased quality of life. Around half of the GPA/MPA patients and one-third of the others had heard about avacopan, and 68% of patients (similarly in both groups) stated they would prefer being the first to take a very new medication, such as avacopan, instead of prednisone. CONCLUSIONS: Ranking given to some GC-related SEs may differ between patients and physicians. GC toxicity/SE indexes should reflect this difference.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

Drug retention rate and predictive factors of drug survival for secukinumab in radiographic axial spondyloarthritis.

The drug retention rate has been an important indicator for evaluating the treatment tolerance. Unfortunately, our knowledge of the secukinumab retention rate in radiographic axial spondyloarthritis (r-AxSpA) is limited. The objective of this study was to assess the retention rate of secukinumab and evaluate predictive factors of drug survival based on data from a real-life cohort. We retrospectively assessed 147 r-AxSpA patients between May 2018 and January 2020 from the HUR-BIO database. Secukinumab retention rates were analyzed using the Kaplan-Meier method and Cox proportional hazard model was used for predictors factors. The global retention rate of secukinumab was 55% at 12 months. r-AxSpA patients with obesity had a lower frequency of secukinumab discontinuation (29% vs. 50%, p = 0.013) in comparison r-AxSpA patients without obesity. In multivariate analysis, multiple TNFi usage had a higher risk of secukinumab discontinuation [HR 1.99 (1.09-3.62), p = 0.024]; on the other hand, obesity had a lower risk [HR 0.45 (0.27-0.90), p = 0.008]. Except for not using multiple TNFi, this real-life analysis showed for the first time that obesity is not an adverse risk factor for secukinumab drug retention in r-AxSpA. Secukinumab, which is an interleukin-17A inhibitor, could act via a different pathway than tumor necrosis factor inhibitors (TNFi). The identification of predictive factors such as obesity that may affect the individual drug selection may provide more appropriate biologic treatment strategies for r-AxSpA.

Pulmonary hypertension in Behçet's disease: echocardiographic screening and multidisciplinary approach.

BACKGROUND: Little is known about the prevalence and causes of pulmonary hypertension (PH) in Behçet's disease (BD). This study was conducted to determine the prevalence and causes of PH in BD. METHODS: In this descriptive study, we screened 154 patients with BD for PH using transthoracic echocardiography between February 2017 and October 2017. An estimated systolic pulmonary arterial pressure (sPAP ≥ 40 mmHg) was used as the cutoff value to define PH. Patients with BD were categorized into 5 groups according to organ involvement including mucocutaneous/ articular, ocular, vascular, gastrointestinal, and neurologic involvement. Additional laboratory and imaging results were obtained from hospital file records to determine the causes of PH. RESULTS: PH was detected in 17 (11%) patients. Nine (52.9%) of these patients had group II PH (due to left heart disease), 4 (23.5%) had IV PH (due to pulmonary arterial involvement), and 1 had III PH (due to chronic obstructive lung disease). The frequency of PH was higher in BD patients with vascular involvement than those without (52.9% vs 28.5%; p = 0.04). Among 10 patients with pulmonary artery involvement (PAI) 4 (40%) had PH. Although the vascular BD group had the highest rate of PH, we observed no statistically significant difference in the frequency of PH between the predefined BD subgroups. DISCUSSION: : PH is not rare in patients with BD. The majority of BD patients with PH are in group II or IV PH. Patients with vascularinvolvement carry a higher risk for the development of PH. Monitoring BD patients with PAI should be considered for the development of group IV PH.

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Comprehensive assessment and outcomes of patients with chronic periaortitis.

OBJECTIVES: Chronic periaortitis (CP) is a less known but more frequently diagnosed fibro-inflammatory disorder, but we know little about it and data regarding follow-up and outcome are still very limited. This study aims to identify the clinicopathologic, laboratory, and radiologic features, as well as outcomes of CP patients. METHODS: Patients with CP from HUVAC database were included in the study. CP was diagnosed based on compatible imaging findings and histopathological evaluation (if available), in addition to clinical findings. Demographics, laboratory, clinical, and imaging data were retrospectively reviewed from medical records. RESULTS: A total of 51 (male/female:37/14) patients were included in the study. Median (IQR) age was 63 (53-69) years and follow-up duration was 40 (4-60) months. 32 of the patients were IgG4-related CP. The most common form of CP in our cohort was idiopathic retroperitoneal fibrosis (82%), followed by inflammatory abdominal aortic aneurysms (12%) and peri-aneurysmal retroperitoneal fibrosis (8%). 8 (15.6%) patients had thoracic periaortitis and 16 (31.6%) venous involvement. Cyclophosphamide (CYC) combined with steroids was the most preferred treatment modality (43%), followed by rituximab (RTX) (31.3%). Follow-up imaging was done after a median (IQR) of 7(3-11) months, 30% of the patients were stable and 64.1% showed regression. A total of 18 (35.2%) had been taken off therapy at the last visit. CONCLUSIONS: Idiopathic retroperitoneal fibrosis was the most frequent presentation, whereas 15.6% of patients had thoracic involvement. Venous involvement was also not uncommon. Optimal time for follow-up imaging was determined as 6-9 months. Steroids along with CYC/RTX had a favourable outcome in the treatment of these patients.

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

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

Cognitive Status is Better in Older Adults under Colchicine Treatment: A Case-Control Study.

PURPOSE: We aimed to investigate the effects of colchicine, an important anti-inflammatory agent, on cognitive functions in a geriatric population diagnosed with gout or osteoarthritis by comparing it to non-colchicine users. METHODS: 138 geriatric patients (67 colchicine users and 71 non-users) were enrolled. Within comprehensive geriatric assessment (CGA), cognitive status assessment via Mini-Mental State Examination test (MMSE), Quick Mild Cognitive Impairment Screening test (Qmci), clock drowning test (CDT), and digit span tests were performed. RESULTS: Median age was 68 (65-72), and there were 82 female (59.4%) patients. The scores of CDT, Backward Digit Span Test, MMSE-Total, MMSE-Attention, MMSE-Motor Function, Qmci-Total Score, Qmci-Clock drawing, and Qmci-Logical Memory were significantly higher in the colchicine user group (p < .005), showing better cognitive function. Adjusted model analysis showed that colchicine usage is independently correlated with higher Qmci-Total Score and Qmci-Logical Memory Score (For Qmci total score ß = 7.87 95%CI = 5.48-10.27, p = <0.0001, and for Qmci Logical memory score ß = 3.52, 95%CI = 2.12-4.91, p = <0.0001). CONCLUSION: To the best of our knowledge, this is the first study revealing that colchicine usage is associated with better cognitive performance in older adults. Further investigations with a prospective, larger-sampled and randomized design are needed to show the causal relationship between colchicine and cognition.

Pleuroparenchymal fibroelastosis in systemic sclerosis-associated interstitial lung disease.

BACKGROUND: To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared. RESULTS: PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

Predictors of persistent inflammation in familial Mediterranean fever and association with damage.

OBJECTIVE: Persistent inflammation is an insidious and less studied feature of FMF. We investigated clinical determinants of persistent inflammation and its associations with individual damage items. METHODS: This is a cross-sectional analysis of 917 FMF patients, who fulfilled the Tel Hashomer criteria and had at least 6 months' follow-up. Patients were stratified based on whether they had persistent inflammation. We used logistic regression analysis to investigate independent predictors of persistent inflammation and the associated individual damage items. RESULTS: One hundred and forty-two (15%) patients had persistent inflammation. Active FMF (54%) was the most prominent reason for the persistent inflammation. Spondylarthritis (16%), other inflammatory arthritis (8%) and IBD (2%) were other frequent reasons. Male gender, history of exertional leg pain, inflammatory comorbidities, M694V homozygosity, colchicine resistance, lower education levels and musculoskeletal attack dominance were found to be the independent predictors of persistent inflammation. Earlier disease onset led to a tendency towards persistent inflammation. Patients with persistent inflammation were more likely to suffer damage. There is an increased risk of developing proteinuria, amyloidosis and renal insufficiency. CONCLUSION: We identified, for the first time, the predictors of persistent inflammation in adult FMF patients and related individual damage items of the Autoinflammatory Disease Damage Index. Persistent inflammation is insidious and one of the chief causes of damage; therefore, especially patients with these predictors should be followed up more closely. If detected, underlying inflammatory comorbidities should be assessed meticulously as early detection and proper treatment strategies may favourably impact the natural history of the disease.

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

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

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.

Factors associated with damage in patients with familial Mediterranean fever.

OBJECTIVES: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage. METHODS: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes. RESULTS: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score. CONCLUSIONS: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.

Familial Mediterranean fever is associated with a wide spectrum of inflammatory disorders: results from a large cohort study.

Familial Mediterranean fever (FMF) is characterized by recurrent short-lived/self-limiting inflammatory attacks. Besides these, a substantial number of patients with FMF present with a variety of other inflammatory diseases; however, this issue has not been systematically studied previously. Hence, we aimed to investigate the frequency of inflammatory comorbid diseases in a large FMF cohort. All patients were recruited from "FMF in Central Anatolia (FiCA) Cohort", comprising 971 (mean age 35.3 ± 12 years, 61.5% female) adult subjects. All patients fulfilled Tel Hashomer criteria. Demographic data, FMF disease characteristics, MEFV gene mutations, and comorbid inflammatory diseases were meticulously questioned, and laboratory features and genotype data were retrieved from hospital records. There were comorbid inflammatory diseases in 205 (21.1%) patients. The most common inflammatory disease was spondyloarthritis (12.9%). Other remarkable inflammatory disorders were psoriasis, immunoglobulin A vasculitis/Henoch-Schönlein purpura, Behçet's disease and inflammatory bowel diseases. Cryptogenic organizing pneumonia is a newly defined entity in our cohort which is seemed to be associated with FMF (0.3%). Number of patients with persistent inflammation was higher in those with comorbid diseases (p < 0.001). Our results suggest that FMF is commonly associated with other inflammatory diseases. Therefore, clinicians should be cautious about comorbid inflammatory diseases in FMF patients, particularly in those with persistent inflammation. Identification of pathogenic pathways linking FMF to these diseases warrants further investigations.

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

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

Colchicine intolerance in FMF patients and primary obstacles for optimal dosing

Background/aim: Colchicine is the mainstay of treatment in FMF. However, in daily practice it is not easy to maintain effective colchicine doses in a substantial number of patients due to its side effects. In this study, we aimed to investigate prevalence and risk factors for colchicine side effects that limit optimal drug dosing and cause permanent discontinuation. Materials and methods: All patients were recruited from "FMF in Central Anatolia" (FiCA) cohort, 915 adults with a minimum follow- up time of 6 months during which they had obeyed all treatment instructions. Demographic and anthropometric data, FMF disease characteristics, disease severity, complications, and treatment features were recorded on a web-based registry. Prevalence of colchicine intolerance and characteristics of intolerant patients were analyzed. Results: Effective colchicine doses cannot be maintained in 172 (18.7%) subjects. Main side effects that limit optimal dosing were as follows: diarrhea in 99 (10.8%), elevation in transaminases in 54 (5.9%), leukopenia in 10 (%1.1), renal impairment in 14 (1.3%), myopathy in five (0.5%), and allergic skin reaction in two. Colchicine had to be permanently ceased in 18 (2%) patients because of serious toxicity. Male sex and obesity were found to be associated with liver toxicity, and having a normal body weight was associated with diarrhea. Chronic inflammation and proteinuria were more common in colchicine-intolerant patients, and they had reported more frequent attacks compared to those tolerating optimal doses. Conclusion: Colchicine intolerance is an important problem in daily clinical practice, mainly due to diarrhea and liver toxicity. Suboptimal colchicine dosing is associated with complications.