The value of a repeat MRI examination of the sacroiliac joints following an inconclusive initial examination.

OBJECTIVE: Assess the diagnostic utility of repeat sacroiliac joint (SIJ) magnetic resonance imaging (MRI) examinations following an inconclusive initial examination performed for suspected sacroiliitis. METHOD: Subjects with > 1 SIJ MRI examinations, an inconclusive first scan and at least 6 months interval between scans, were included. All scans were evaluated for the presence of structural/active SIJ lesions as well as any other pathology. Clinical data was extracted from the patients' clinical files, and any missing data was obtained by a telephone interview. Diagnosis and active/structural scores were compared between first and follow-up examinations (t test). RESULTS: Seventy-one subjects were included in the study, 77.4% females, mean age 41.0 ± 15 years, mean time interval between exams 30.4 ± 25.24 months. Twelve subjects performed > 2 scans. In only two subjects (2.81%), both females, MRI diagnosis changed from inconclusive to definite sacroiliitis. None of the subjects with > 2 scans had evidence of sacroiliitis in any of the following MRI examinations. Significant differences were observed between the scores of active SIJ lesion of the first and follow-up MRI (1.51/1.62, p = 0.02) but not for scores of structural lesions (1.22/1.68, p = 0.2). CONCLUSIONS: Repeat SIJ MRI when the first MRI is inconclusive for sacroiliitis is more valuable in ruling out than in securing diagnosis of sacroiliitis. We suggest that when MRI findings are inconclusive, decision-making should be based on clinical data.

No correlation between diffuse idiopathic skeletal hyperostosis and coronary artery disease on computed tomography using two different scoring systems.

BACKGROUND: An association between diffuse idiopathic skeletal hyperostosis (DISH) and a history of coronary artery disease (CAD) was previously reported. PURPOSE: To investigate the association between DISH and CAD as assessed using the coronary artery calcification score (CACS) and the CAD-Reporting and Data System (CAD-RADS) score in patients with symptomatic chest pain. MATERIAL AND METHODS: Consecutive cardiac CT scans performed before and after IV contrast administration were evaluated for CACS (Agatston method), CAD-RADS, and the presence of DISH. The association of DISH with the presence and extent of CACS/CAD-RADS scores was analyzed with and without adjustment for known atherosclerotic risk factors. RESULTS: The study cohort included 268 individuals (157 men, 111 women; median age = 54 years). DISH was present in 65 (24.3%) individuals. CACS was significantly higher in the DISH group compared to the non-DISH group in the univariate analysis (median CACS DISH = 2, range = 0-80.5 vs. median CACS non-DISH = 0, range = 0-11; P < 0.005) but this association did not persist on multivariate analysis. There was a positive trend toward higher CAD-RADS scores in the DISH group (P = 0.03) but after adjustment for age, male sex, and family history, this tendency was not significant. CONCLUSION: No independent association was found between the presence of DISH and CACS and CAD-RADS scores. Our findings suggest a more complex and possibly non-causal relationship between coronary artery disease and DISH.

Osteophytes' position in subjects with DISH and right-sided aorta: verification of the 'aortic pulsation protective effect' theory.

OBJECTIVES: To validate in a large cohort with right-sided aorta the theory that thoracic right-sided flowing osteophytes in DISH results from a 'protective' effect of the pulsating descending left-sided thoracic aorta. METHODS: Chest CTs of patients with DISH and right-sided aorta and controls with DISH and left-sided aorta were evaluated and compared on each intervertebral space (IS) for the location of the aorta (right, left, centre) and the location of the osteophyte relative to the aorta (contralateral, ipsilateral, bilateral). RESULTS: The study and control cohorts included 31 and 35 subjects, respectively (male 22/9 and female 27/8; median age 64.8/65.3 years; P = 0.86). Osteophytes contralateral to the aorta's location were recorded in the majority of ISs in both the study and control groups (47% and 60%, respectively; P > 0.05), while ipsilateral osteophytes were recorded in 6.9% and 7.7%, respectively (P = 0.002). Bilateral osteophytes located to the right and the left of the aorta were significantly more prevalent in the study group compared with the controls (17.2% and 5.4%, respectively; P = 0.04). CONCLUSIONS: Aortic pulsation plays an important role in inhibiting the development of osteophytes and results in the majority of contralateral osteophytes on both right-sided and left-sided aortas. However, since both ipsilateral and bilateral osteophytes were not at all rare in both groups, other parameters, which are yet to be established, probably contribute to the location of osteophytes.

Safety of the BNT162b2 mRNA COVID-19 vaccine in patients with familial Mediterranean fever.

OBJECTIVES: Evidence suggests a possible association between the COVID-19 vaccine and autoimmune disease flares or new onset of various autoinflammatory manifestations, such as pericarditis and myocarditis. The objective of this study was to assess the safety of an mRNA-based BNT162b2 anti-COVID-19 vaccine in individuals with FMF, a prototypic autoinflammatory disease. METHODS: Patients participating in this study fulfilled the criteria for diagnosis of FMF, were older than 18 years and received at least one dose of the vaccine. Data on baseline characteristics, features of FMF, post-vaccination side effects, and disease flares were acquired using electronic medical files and telephone interviews. RESULTS: A total of 273 FMF patients were recruited for the study. >95% were vaccinated with two doses of the vaccine. The rates of local reactions following the first and second vaccine doses were 65.5% and 60%, respectively, and 26% and 50.4%, respectively, for systemic adverse events. These rates are lower than those reported for the general population from real-world and clinical trial settings. Postvaccination FMF activity remained stable in most patients. None of the patients reported an attack of pericarditis or myocarditis, considered the most serious vaccine-associated adverse events. Patients with a more active FMF disease and patients harboring the M694V mutation had a significantly higher rate of post-vaccination systemic side effects and attacks. CONCLUSION: The BNT162b2 mRNA COVID-19 vaccine is safe in patients with FMF. Our results support the administration of this vaccine to FMF patients according to guidelines applicable to the general population.

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features including uveitis, intestinal and lung apical inflammation and psoriasis. Putative associations between AS and neurologic disorders has been relatively overlooked. The purpose of this study is to assess the link between AS and major neurologic disorders and whether treatment with Tumor-Necrosis-Factor inhibitors (TNFi) has an impact on that association. METHODS: A retrospective cross-sectional study was carried out based on the Clalit Health Services (CHS) computerized database. AS patients were compared to age- and gender-matched controls with respect to the proportion of Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. RESULTS: 4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95%Confidence-interval(CI) 1.13-1.87], p = 0.003), epilepsy (OR 2.33 [95%CI 1.75-3.09] p < 0.0001) and PD (OR 2.75 [95%CI 2.04-3.72], p < 0.0001), whereas no statistically significant association was found for MS. Association with PD remained significant in the multivariate analysis (OR 1.49 [95%CI 1.05-2.13],p = 0.027). Within AS patients, the use of TNFi (OR 0.10 [95%CI 0.01-0.74], p = 0.024) were associated with a lowered risk of developing AD. CONCLUSION: AS is positively associated with AD, PD, and epilepsy but not MS. AS patients treated with TNFi have lower rates of AD.

The prevalence of sacroiliitis on abdominal MRI examinations of patients with Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA), a systemic large-vessel vasculitis, was reported to have high incidence of spondyloarthropathy. PURPOSE: To evaluate the prevalence of inflammatory sacroiliitis in patients with TA that underwent abdominal/pelvic magnetic resonance imaging (MRI) examinations as part of their vasculitis work-up. MATERIAL AND METHODS: Consecutive abdominal/pelvic MRI examinations of 34 patients with TA fulfilling the 1990 ACR criteria and 34 age- and gender-matched controls performed between 2008 and 2020 were retrospectively reviewed for the presence sacroiliitis. The presence of active and structural lesions was scored twice (with a one-month interval between reads) by one reader. Structural lesions were also evaluated on computed tomography, when available, and correlated to MRI findings. Clinical data were extracted from the patients' clinical files. MRI scores were compared between the study and control groups and correlated with the clinical data. RESULTS: Sacroiliitis was evident in 11.7% of the TA group examinations compared to 0.3% in the control group (P = 0.6). Participants with TA had significantly more erosions and fat deposition compared to the control group (Study: 0.01/0.03, Control: 0/0, P = 0.03/0.003, respectively). However, mean sacroiliitis score was not significantly different (Study: 1.06, Control: 0.78, P = 0.015). Of the four patients with TA and sacroiliitis, 3 (75%) had a diagnosis of inflammatory bowel disease (IBD). CONCLUSION: Sacroiliitis was detected in 11.7% of abdominal MRI examinations of patients with TA, 75% of which had associated IBD, suggesting that both IBD and sacroiliitis should be routinely screened in the TA population as their presence may influence treatment decisions.

The frequency of sacroiliitis on MRI in subjects over 55 years of age.

OBJECTIVE: To evaluate the frequency of sacroiliitis in older subjects. MATERIALS AND METHODS: Consecutive MRI examinations of the sacroiliac joints (SIJs) performed for suspected sacroiliitis (2005-2019) in patients ≥ 18 years were retrospectively evaluated for the presence of active/structural lesions and were categorized for the presence/absence of sacroiliitis. Clinical and imaging parameters were compared between subjects with sacroiliitis according to age groups < 40 years, 40-55, and > 55 years. Clinical parameters including inflammatory back pain (IBP) and other spondyloarthritis (SpA) features were retrieved from the medical records. RESULTS: A total of 431 patients with SIJs MRI were evaluated: median age, 44 [IQR 35-54]; female:male 267(62%):164(38%). Sacroiliitis was diagnosed in 89 (20.6%) subjects-median age, 41 years [IQR 32-54], 52% females- and was equally prevalent among the different age groups: > 40 years old, 23.6%; 40-55, 20%; and > 55 years old, 17%, p = 0.43, with active/structural lesions equally dispersed. Older patients (> 55) started suffering from back pain at an older age and had a longer delay in diagnosis. Gender distribution, the presence of IBP, and other SpA features were no different in patients < 45 and > 55 years of age. CONCLUSIONS: The frequency of sacroiliitis on SIJs-MRI in subjects > 55 years is similar to its frequency in younger subjects and is associated with the same type and magnitude of active and structural MRI lesions. Clinical parameters such as IBP and additional SpA features are similarly prevalent in older and younger subjects suggesting they suffer from the same disease and differing only in age of presentation.

The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease.

Familial Mediterranean fever (FMF), the most frequent monogenic autoinflammatory disease, is manifested with recurrent and chronic inflammation and amyloid A (AA) amyloidosis, driven by overproduction of interleukin 1 (IL-1) through an activated pyrin inflammasome. Consequently, non-responsiveness to colchicine, the cornerstone of FMF treatment, is nowadays addressed by IL-1- blockers. Each of the two IL-1 blockers currently used in FMF, anakinra and canakinumab, has its own merits for FMF care. Here we focus on anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, and explore the literature by using PubMed regarding the utility of anakinra in certain conditions of FMF. Occasionally we enrich published data with our own experience. To facilitate insights to anakinra role, the paper briefs some clinical, genetic, pathogenetic, and management aspects of FMF. The clinical settings of FMF covered in this review include colchicine resistance, AA amyloidosis, renal transplantation, protracted febrile myalgia, on- demand use, leg pain, arthritis, temporary suspension of colchicine, pediatric patients, and pregnancy and lactation. In many of these instances, either because of safety concerns or a necessity for only transient and short-term use, anakinra, due to its short half-life, is the preferred IL-1 blocker.

Anakinra for colchicine refractory familial Mediterranean fever: a cohort of 44 patients.

OBJECTIVE: FMF is an autoinflammatory disease of genetic origin. Colchicine is the mainstay of treatment for the prevention of attacks and long-term complications but 5-10% of FMF patients are resistant to colchicine therapy. The aim of our study was to investigate the real-life safety and efficacy of anakinra in a cohort of patients with colchicine-resistant FMF. METHODS: In this retrospective study, patients treated with anakinra for colchicine-resistant FMF between 2010 and 2018 were identified using the computerized database of Sheba Medical Center and enrolled in the study. Data from structured clinical files were analysed to evaluate the efficacy and safety outcomes. To assess efficacy, we used the Global Assessment Score (GAS), a measure comprised of three different domains: number of attacks per month, duration of attacks and number of sites involved in the attacks. Reported adverse events were compiled. RESULTS: A total of 44 patients (24 female) were treated with anakinra. Of these patients, 75% were homozygous for the M649V mutation. The mean duration of treatment was 18 months. The GAS decreased significantly from 6.6 (IQR 5.3-7.8) before treatment to 2 (IQR 0-4.2) while on treatment (P < 0.001). During anakinra treatment, six hospitalizations were reported (three due to related adverse effects). In addition, 11 patients suffered from injection site reactions (5 ceased treatment). Twelve patients reported mild side effects. CONCLUSION: Treatment with anakinra is beneficial for the majority of colchicine-resistant FMF patients and is relatively safe.

Effect of interleukin-1 inhibition in a cohort of patients with colchicine-resistant familial Mediterranean fever treated consecutively with anakinra and canakinumab.

OBJECTIVES: To evaluate the efficacy of IL-1 blockers in a cohort of patients with colchicine-resistant familial Mediterranean fever (crFMF) treated consecutively with anakinra and canakinumab. METHODS: Patients with crFMF treated with anakinra and canakinumab in any order were identified using the computerised database of Sheba Medical Centre. Background characteristics of the patients, reason for switching IL-1 inhibitor, and frequency of attacks under colchicine only, anakinra, and canakinumab were extracted from the computerised patient files. Patients were then interviewed for patient-reported outcomes. RESULTS: A total of 46 patients in our clinic were prescribed canakinumab for crFMF after previous anakinra treatment, whereas no patients who switched treatment from canakinumab to anakinra were identified. Of those, 23/46 patients (50%) discontinued anakinra due to inadequate response (11 of them with secondary failure after a good initial response). Frequency of flares was significantly decreased following switch to canakinumab from anakinra treatment (p<0.01). After the switch to canakinumab, the median duration of flares, the severity of pain during a flare, and the patient's global assessment of disease activity were all significantly decreased (p≤0.01), according to the reports from the patients. CONCLUSIONS: Canakinumab is an effective treatment for FMF after failure of anakinra due to any cause.

Rituximab for refractory manifestations of the antiphospholipid syndrome: a multicentre Israeli experience.

OBJECTIVES: The clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and related to anti-phospholipid antibodies (aPL). There is some evidence that B cells are involved in the pathogenesis of this condition. Thus the ability of rituximab (RTX) to deplete B cells makes it an appealing potential therapy for refractory antiphospholipid syndrome (APS). Real world data on RTX treatment of APS are still lacking. This study was conducted to report outcomes of RTX administration in the treatment of different aspects of APS. METHODS: This is a retrospective case series study on APS patients from 3 medical centres in Israel who were treated with RTX during 2010-2019 for refractory manifestations of APS including diffuse alveolar haemorrhage, recurrent thrombosis, cytopenia, neurological and skin manifestations. Medical records were reviewed regarding the clinical indication for RTX treatment, concomitant medications, RTX protocol, aPL status and response to treatment. Outcomes were defined as complete response if full resolution of the "indicated manifestation" was achieved and maintained for at least 12 months, partial response or no response. RESULTS: We identified 40 APS patients who were treated with RTX for refractory manifestations of this condition, of whom, 24 patients (60%) were female with a mean age of 40 years, and 31 patients (78%) were diagnosed with primary APS. A favourable response to RTX was documented in 32 patients (80%) including a complete response in 22 patients (55%). Response to RTX treatment was associated with a rituximab protocol of 375mg/m2 x 4 compared to a fixed dose of 1000 mg x2 (100% vs. 65%; p=0.01). Complete response was associated with a decrease in aPL titres within 4-6 months post treatment, whereas no significant change in aPL titres was observed in patients with partial or no response. CONCLUSIONS: Consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. In this cohort, treatment protocols were associated with outcomes. Although further studies are required to verify our observations, our data support a plausible role for B cell depletion in refractory APS.

Real-world effectiveness of tofacitinib in patients with rheumatoid arthritis: a prospective observational study.

OBJECTIVES: Tofacitinib is an approved treatment for rheumatoid arthritis (RA), but data on its use in the "real-world" are limited. We sought to analyse tofacitinib drug survival in the Israeli registry and compare it to other biologic agents. METHODS: We included RA patients treated with tofacitinib, etanercept, golimumab, tocilizumab, or abatacept between 2010-2019. The primary endpoint was event-free survival (EFS), defined as the time from treatment initiation to a treatment failure event from any cause (i.e., inefficacy or intolerability). EFS was compared between agents using Cox regression and Kaplan-Meier analysis, stratifying patients by treatment line. RESULTS: A total of 964 eligible treatment courses were included (tocilizumab [325], etanercept [284], abatacept [127], tofacitinib [139], and golimumab [109]). In a univariate analysis, EFS with tofacitinib in the complete cohort was similar to etanercept, golimumab, and abatacept but was lower than tocilizumab) 3-year EFS 43% vs. 53%, HR 0.65). In a multivariable analysis, tofacitinib was similar to all other drugs, except for etanercept, which was inferior (HR 1.70); advanced treatment line was also associated with greater risk for failure (HR 1.64). In a univariable analysis stratified by the treatment line, tofacitinib had similar or better drug survival than other agents in the first and second lines. In the third line and beyond, tocilizumab had a higher EFS compared to tofacitinib (HR 0.57). CONLUSIONS: Drug survival with tofacitinib is related to treatment line. Early introduction is associated with similar or better survival than other agents, whereas tocilizumab was superior in the third line or later.

The risk for severe COVID 19 in patients with autoimmune and/or inflammatory diseases: First wave lessons.

Data regarding the risk for severe COVID19 in patients with autoimmune or inflammatory diseases are scarce. To estimate the risk of those patients to develop a more severe COVID19 infection All active patients and those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were identified in a single tertiary center. The charts of those tested positive for COVID19 between 1 March 2020 and 31 May 2020 reviewed including demographics, co-morbidities, and medications. COVID19 outcome of those with dermatologic and/or rheumatologic autoimmune/inflammatory diseases were compared to COVID19 infected matched controls without an autoimmune/inflammatory background. Overall, 974 of 381 268 active patients were tested positive for COVID19, including 35 out of 13 225 with dermatologic and/or rheumatologic autoimmune/inflammatory diseases. No statistically significant difference in severity of COVID19 infection or mortality rate was found. The rate of asymptomatic, mild, moderate, severe/critical and fatal COVID19 infection was 11.4%, 37.1%, 22.8%, 11.4%, and 17.1%, respectively, for the patients with autoimmune diseases and 17.8%, 45.8%, 10.9%, 6.8%, and 18.4%, respectively for the controls . Patients with autoimmune/inflammatory diseases seem not to develop a more severe COVID19 infection than controls.

Autonomic Nervous System Indices in Patients with Systemic Sclerosis without Overt Cardiac Disease.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that may affect the heart and the autonomic nervous system (ANS). There is little knowledge regarding the degree of ANS involvement in SSc patients with unknown cardiac disease. OBJECTIVES: To evaluate cardiac and pupillary autonomic functions in patients before cardiac involvement has emerged. METHODS: The study comprised 19 patients with SSc and 29 healthy controls. Heart rate variability (HRV) analysis for time and frequency domains, as well as deep breathing test and Ewing maneuvers, were performed in all patients. Automated pupillometry for the evaluation of pupillary diameter and pupillary light reflex was completed in 8 SSc patients and 21 controls. RESULTS: Both groups had similar characteristics, except for medications that were more commonly or solely prescribed for SSc patients. Compared with control subjects, the SSc patients had significantly lower HRV parameters of NN50 (15.8 ± 24.4 vs. 33.9 ± 33.1, P = 0.03), pNN50 (4.9 ± 7.4% vs.10.8 ± 10.8%, P = 0.03), and triangular index (11.7 ± 3.4 vs. 15.7 ± 5.8, P = 0.02). Abnormal adaptive responses in heart rate changes were recorded during deep breathing tests and Ewing maneuvers. There was no significant difference in any of the pupillometric indices or other HRV parameters within groups. CONCLUSIONS: SSc patients may manifest cardiac autonomic dysfunction, while their autonomic pupillary function is seemingly spared. The role of certain medications, the significance of differential organ involvement, as well as the prognostic value of our findings should be evaluated in future studies.

The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.

BACKGROUND: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. MATERIALS AND METHODS: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). CONCLUSIONS: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

Enthesopathy of the anterior chest wall joints in patients with diffuse idiopathic skeletal hyperostosis (DISH): a retrospective analysis of computed tomography scans.

PURPOSE: To evaluate and characterize anterior chest wall (ACW) joint's enthesopathy on CT scans in patients with DISH compared with age- and gender-matched control group. MATERIAL AND METHODS: Retrospective evaluation for enthesopathy features of ACW joints-sterno-clavicular (SCJ), manubrio-sternal (MSJ), costo-sternal 1-7 (CSJ)-on chest CT scans of subjects with DISH (Resnick criteria) and of age- and gender-matched control subjects was performed. 183 subjects (DISH: 92, control: 91); male:female: 126:57, average age: 71.7 years (range 50-94) were evaluated. Total enthesopathy scores per subjects and per each joint were compared. RESULTS: Total enthesopathy score of ACW joints was significantly higher among DISH compared to controls (64.03 ± 15.1, 50.47 ± 12.4, p < 0.001). At joint level, SCJ and CSJ enthesopathy, but not MSJ was significantly more prevalent in DISH compared to controls. CONCLUSION: ACW joints' enthesopathy as seen on CT scans, an entity not included in the Resnick classification criteria, is common among DISH subjects. The difference between SCJ and CSJ prevalence compared to MSJ may result from different joint type. ACW joints' enthesopathy may be considered to be included in future modified radiographic criteria for DISH.

A Study of the Efficacy and Safety of Subcutaneous Injections of Tocilizumab in Adults with Rheumatoid Arthritis.

BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.

[IS THERE A CORRELATION BETWEEN CARRIAGE OF AN MEFV MUTATION AND GOUT?]

INTRODUCTION: Gout is an inflammatory condition mediated by Interleukin-1-beta (IL-1ß). A mutation in the MEFV gene (the gene related to Familial Mediterranian fever) may cause an elevation in IL-1ß, and is associated with a variety of inflammatory conditions. Reports in the literature are inconsistent as to whether a mutated MEFV gene is related to the phenotype of gout. OBJECTIVES: To assess whether a carriage state of a mutation in the MEFV gene correlates with the expression and severity of gout. METHODS: A total of 73 patients, 50 with gout and 23 with hyperuricemia were examined for an MEFV mutation. Carriage rate was compared between hyperuricemic and gout patients, and disease activity measures were compared between MEFV mutation carriers and non-carriers. RESULTS: We did not find a statistically significant difference in the carriage rate of an MEFV mutation between gout patients and hyperuricemic patients without gout, nor did we find a correlation between MEFV mutation carriage and gout severity. CONCLUSIONS: Further large-scale studies should be conducted in order to determine a possible correlation between MEFV mutation carriage and gout.

The prevalence and clinical effect of immunogenicity of TNF-α blockers in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the prevalence of immunogenicity of TNF-α blockers in axial spondyloarthritis (SpA) patients and to assess the effect of immunogenicity on drug levels and clinical response. METHPDS: Patients with axial SpA treated with either infliximab (INF), adalimumab (ADA) or etanercept (ETN) were recruited to our observational cross-sectional study. Demographic and clinical data were collected and disease activity scores were assessed. Drug trough levels and anti-drug antibodies were measured in serum samples and collected before the next administration. RESULTS: Thirty-nine patients with axial SpA with a mean age of 46.3±12.7 (10 women) were recruited to the study (14 receiving INF, 16 ADA and 9 ETN). Patients' mean therapy duration was 50.6 months (±46.4) and 6 (15%) of them were using MTX concomitantly with the TNF-α blockers. Anti-drug antibodies were found in 6 (15%) patients (4 with INF and 2 with ADA), all of which had undetectable drug level. No anti-drug antibodies were detected in patients treated with ETN. Immunogenicity was associated with higher BASDAI (Bath Ankylosing Spondylitis Disease Index), ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) and ASDAS-ESR. CONCLUSIONS: Axial SpA patients failure to respond to TNF-α blockers may be at least partially related to immunogenicity. Measurement of anti-drug antibodies and drug levels in these patients may assist in determining further treatment strategies.

Degenerative changes of the thoracic spine do exist in patients with diffuse idiopathic skeletal hyperostosis: a detailed thoracic spine CT analysis.

Background Degenerative intervertebral disease (DID) is an exclusion criterion in the Resnick and Niwayama radiographic classification for diffuse idiopathic skeletal hyperostosis (DISH). However, although DID was previously described in DISH, no systematic computed tomography (CT) analysis has been reported so far. Purpose To assess for the presence and prevalence of such changes on CT examinations of the thoracic spine of individuals with DISH. Material and Methods Intervertebral space (D1-L1) on chest CT examinations of DISH patients was retrospectively evaluated for the presence of DID. Parameters evaluated were disc space height, disc protrusion, subchondral cysts/sclerosis, Schmorl nodes, vacuum phenomenon, and posterior elements including costovertebral and facet joints. Parameters were compared with two age- and gender-matched control groups of individuals whose entire spine CT lacked evidence of DISH (Control 1 individuals < 2 flowing osteophytes, Control 2 individuals < 4 and ≥ 2 flowing osteophytes). Results A total of 158 participants (DISH/Control 1/Control 2 = 54/54/50; 106 men, 52 women; average age = 70.6 years) were evaluated. Average intervertebral disc height was significantly lower in the DISH group compared with both control groups (DISH/Control 1/Control 2 = 4.55/5.13/5.01 mm, P < 0.001). Costovertebral degenerative changes were more prevalent in DISH patients ( P < 0.05) and, except for vacuum phenomenon (more prevalent in controls), other DID changes were as prevalent in DISH as in controls. Conclusion The presence of degenerative intervertebral changes on thoracic CT should not deter from diagnosing DISH. Thus, the radiographic Resnick and Niwayama DISH criteria cannot be directly adapted to CT.