Publications by authors named "Victoria Furer"

38 Publications

CD4 LAG-3 T Cells are Decreased in Active Psoriatic Arthritis Patients and Their Restoration In Vitro is Mediated by TNF Inhibitors.

Clin Exp Immunol 2021 Jul 26. Epub 2021 Jul 26.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte-activation gene (LAG)-3 is one of the regulatory receptors expressed on T cells and in a soluble form. LAG-3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non-MDA), and healthy controls. In cultured in vitro peripheral blood mononuclear cells (PBMCs), LAG-3 expression on CD4 T cells was similar in both MDA PsA patients (7.5 ± 0.9) (n=14) and healthy controls (7.8 ± 0.6) (n=15) but significantly lower in non-MDA PsA patients (3.1 ± 0.3) (n = 13) (p < 0.0001). An inverse correlation between PsA clinical disease activity and %LAG-3 CD4 T cells in vitro was observed: Composite Psoriatic Disease Activity Index r=-0.47, p < 0.02 and Psoriatic Arthritis Disease Activity Score, r=-0.51, p < 0.008. In vitro co-culture of CD4 T cells with anti-TNF or anti-IL-17A had no effect on LAG-3 expression in MDA PsA patients and healthy controls. In non-MDA patients, anti-TNF, but not anti-IL-17A, restored the %CD4 LAG-3 T cells (7.9 ± 0.9 and 3.2 ± 0.4, respectively) (p < 0.0004). Lower soluble LAG-3 levels were found in sera of naïve to biologics PsA patients (n = 39) as compared to healthy controls (n = 35) (p < 0.03). Impaired LAG-3 on CD4 T cells may reflect active PsA disease state. Anti-TNFs have potency to up-regulate the CD4 LAG-3 T cells in vitro.
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http://dx.doi.org/10.1111/cei.13646DOI Listing
July 2021

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

Ann Rheum Dis 2021 Jul 2. Epub 2021 Jul 2.

Rheumatology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objective: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS).

Methods: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores.

Results: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models).

Conclusions: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.
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http://dx.doi.org/10.1136/annrheumdis-2021-220562DOI Listing
July 2021

Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study.

Ann Rheum Dis 2021 Jun 14. Epub 2021 Jun 14.

Rheumatology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Introduction: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.

Methods: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.

Results: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.

Conclusion: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.
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http://dx.doi.org/10.1136/annrheumdis-2021-220647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206170PMC
June 2021

Pustular Psoriasis and Associated Musculoskeletal Disorders.

J Rheumatol Suppl 2021 Jun;97:34-38

P.S. Helliwell, MD, PhD, Professor of Clinical Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Harehills Lane, Leeds, and NIHR Leeds Biomedical Research Centre, Leeds, UK.

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.
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http://dx.doi.org/10.3899/jrheum.201673DOI Listing
June 2021

Relationship between religiosity, spirituality and physical and mental outcomes in fibromyalgia patients.

Clin Exp Rheumatol 2021 May-Jun;39 Suppl 130(3):48-53. Epub 2021 Apr 9.

Sackler School of Medicine, Tel Aviv University, and Internal Medicine H, Tel Aviv Sourasky Medical Centre, Israel.

Objectives: The coping mechanisms utilised by patients with the fibromyalgia syndrome (FM) pose a crucial focus of treatment. Previous research points to the positive effects of religiosity and spirituality (R/S) as tools for coping with illness. The role of these factors in coping with chronic pain in FM has not previously been studied. The aim of this study was to evaluate the link between R/S and FM outcomes.

Methods: Fifty-five FM patients (ACR criteria) attending a tertiary rheumatology clinic completed a packet of questionnaires assessing demographic data, levels of religiosity and spirituality (SpREUK) and locus of control (LOC). These variables were then individually assessed for influence on FM outcome measures, using the Fibromyalgia Impact Questionnaire (FIQ), the SF-36, and the Beck Depression Index (BDI).

Results: A high score on SpREUK I (search for meaningful support) was negatively correlated with the Role-Physical (p=0.032) and Role-Emotional (p<0.005) scales on SF-36. Secular patients scored higher on SF-36 domains of "Role limitation due to emotional health" and "General health" (p<0.05). Employment demonstrated a positive correlation with the FIQ (p<0.01), the BDI (p<0.001), and the SF-36 (p<0.05). Physical activity correlated positively with BDI scores (p=0.012) and better scores on SF-36: energy/fatigue (p=0.024), social-functioning (p=0.014) and physical-functioning (p<0.01). No significant correlation was found between LOC (internal versus external) and FM outcomes. No significant correlation was found between SpREUK domains and the BDI.

Conclusions: FM patients do not appear to benefit from high levels of R/S. Physicians should be aware of the impact of R/S on well-being in this population.
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June 2021

Herpes zoster following BNT162b2 mRNA Covid-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series.

Rheumatology (Oxford) 2021 Apr 12. Epub 2021 Apr 12.

Rheumatology.

Objectives: As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness to reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD.

Methods: The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two Rheumatology Departments in Israel.

Results: The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: rheumatoid arthritis (n = 4), Sjogren's syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in 5 cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects.

Conclusion: Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.
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http://dx.doi.org/10.1093/rheumatology/keab345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083327PMC
April 2021

Prevalence of COVID-19 and seroprevalence to SARS-CoV-2 in a rheumatologic patient population from a tertiary referral clinic in Israel.

Intern Med J 2021 05 12;51(5):682-690. Epub 2021 May 12.

Rheumatology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Background: It is unclear if the prevalence of COVID-19 in rheumatologic patients is similar to that of the general population. There are no reports of seroprevalence of SARS-CoV-2 in these patients.

Aims: To investigate prevalence of COVID-19 cases and seroprevalence among rheumatologic patients and the risk factors for infection.

Methods: A cross-sectional study in a rheumatologic population. An online questionnaire was sent on 31 April 2020. Blood samples from 20% sample of patients were drawn for SARS-CoV-2 antibodies. Patients were divided based on autoimmune (AI) diagnosis. Prevalence of COVID-19 by nasopharyngeal swab and by serology (seroprevalence) was compared to national data. Risk factors for infection of SARS-CoV-2 were assessed.

Results: The study group included 1204 patients, 74.5% had an AI diagnosis. The prevalence of COVID-19 was 0.16% in the rheumatologic patient population and 0.22% in the AI group, which was not different from prevalence in Israel on 4 May 2020 (0.18%, P = 0.912 and P = 0.759 respectively). Serologic tests were performed in 242 patients, of which five were found positive pointing to a seroprevalence of 2.07%. Exposure to a known COVID-19 patient was the only significant risk factor for being positive by swab or by serology. AI diagnosis, immunosuppression, corticosteroid, hydroxychloroquine did not influence the risk.

Conclusions: The prevalence of COVID-19 in a population of rheumatologic patients was similar to that of the general population. Mild/asymptomatic cases may be prevalent according to serologic tests. The major risk factor for infection is exposure to a known case of COVID-19, and immunosuppression did not play a role in the risk of infection.
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http://dx.doi.org/10.1111/imj.15202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251200PMC
May 2021

Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis patients.

Rheumatology (Oxford) 2021 Mar 17. Epub 2021 Mar 17.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objective: To report the discrepancies and agreements between ultrasound (US), magnetic resonance imaging (MRI) and radiography of the hand in psoriatic arthritis (PsA), and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA.

Methods: All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK).

Results: The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared to MRI (P < 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85%-96%, PABAK=0.70-0.92), flexor tenosynovitis (93%-98%, PABAK=0.87-0.96), and extensor paratenonitis (95%-98%, PABAK=0.90-0.97). Agreement between US, MRI and radiography was 96%-98% (PABAK=0.92-0.97) for erosions and 71%-93% (PABAK=0.47-0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5-0.86) and extensor paratenonitis (0.63-0.85) than for flexor tenosynovitis (0.1-0.75), while the specificity was high for each pathology (0.89-0.98).

Conclusion: There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.
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http://dx.doi.org/10.1093/rheumatology/keab272DOI Listing
March 2021

Pustular Psoriasis and Associated Musculoskeletal Disorders.

J Rheumatol 2021 Mar 15. Epub 2021 Mar 15.

As part of the supplement series GRAPPA 2020, this report was reviewed internally and approved by the Guest Editors for integrity, accuracy, and consistency with scientific and ethical standards. K. Callis Duffin, MD, MS, Department of Dermatology, University of Utah, Salt Lake City, Utah, USA; H. Bachelez, MD, PhD, Department of Dermatology, Hôpital Saint-Louis, AP-HP, and Laboratory of Genetic Skin Diseases, Imagine Institute, Université de Paris, Paris, France; P.J. Mease, MD, Rheumatology Research, Swedish Medical Center/ Providence St. Joseph Health and University of Washington School of Medicine, Seattle, Washington, USA; C. Rosen, Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada; A. Garg, MD, Chair, Department of Dermatology, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA; E. Zudak, BFA, Vice President, Strategic Partnerships, WCG Trifecta, Indianapolis, Indiana, USA; O. Elkayam, MD, V. Furer, MD, Rheumatology Department, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; J.F. Merola, MD, MMSc, Harvard Medical School, Brigham and Women's Hospital, Department of Dermatology and Department of Medicine, Division of Rheumatology and Immunology, Boston, Massachusetts, USA; J. Chau, GRAPPA Patient Research Partner, Hong Kong; M. Kishimoto, MD, Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan; P.S. Helliwell, MD, PhD, Professor of Clinical Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Harehills Lane, Leeds, and NIHR Leeds Biomedical Research Centre, Leeds, UK. KCD received grants/is an investigator for Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Bristol Myers Squibb, Stiefel, Novartis, Pfizer, Sienna, UCB, Regeneron, Boehringer Ingelheim; is on the speakers bureau for Novartis (nonpromotional only); and is a consultant/on the advisory board for Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Bristol Myers Squibb, Stiefel, Novartis, Pfizer, Sienna, UCB, Ortho Dermatologic, and Boehringer Ingelheim. PJM received research grants, consultation fees, and/or speaker honoraria from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB. AG received grants/is an investigator for the National Psoriasis Foundation, UCB, Incyte; and is a consultant/on the advisory board for AbbVie, Amgen, Asana Biosciences, Bristol Myers Squibb, Boehringer Ingelheim, Incyte, Janssen, Pfizer, UCB, and Viela Biosciences. JFM is consultant and/or investigator for Merck, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres, and Leo Pharma. MK receives consulting fees and/or honoraria from AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma. OE receives consulting fees or honoraria from AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Roche, Pfizer, Boehringer Ingelheim, and Novartis. This paper does not require institutional review board approval. Address correspondence to Dr. K. Callis Duffin, University of Utah, 4A330 Dermatology, SOM, 30 North 1900 East, Salt Lake City, UT 84132, USA. Email:

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement. Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.
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http://dx.doi.org/10.3899/jrheum.201673DOI Listing
March 2021

T cell functions of psoriatic arthritis patients are regulated differently by TNF, IL-17A and IL-6 receptor blockades in vitro.

Clin Exp Rheumatol 2021 Feb 25. Epub 2021 Feb 25.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Objectives: The impact of biologics used in PsA management on T cells is unknown. This study evaluated the effect of tumour necrosis factor-alpha (TNFα), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in PsA patients and healthy controls peripheral blood mononuclear cells (PBMCs).

Methods: A total of 111 PsA patients and 32 healthy controls were recruited. PBMCs were co-cultured in presence of the biologics. T cell activation and proliferation were analysed by flow cytometry and cytokines in supernatants were measured by ELISA. The effect of biologics on lymphocyte proliferation was determined in response to phytohemagglutinin (PHA).

Results: Activated CD4+CD25+ T cells were significantly reduced by adalimumab (ADA) in PsA patients as compared to medium, ixekizumab (IXE), and tocilizumab (TCZ), while in healthy controls, ADA reduced the activated CD4+CD25+ T cells non-significantly. Elevated TNFα and IL-1β levels were produced in supernatants of PsA patients as compared to healthy controls. TNFα, IL-17A, IL-1β, and MMP-3 levels were reduced by ADA compared to medium (p<0.0001, p<0.0004, p<0.04, p<0.04, respectively). IXE reduced IL-17A (p<0.0001) but not the other cytokines. ADA had higher susceptibility to inhibit PHA-induced proliferation in both PsA patients and healthy controls (p<0.03) as compared to IXE and TCZ.

Conclusions: Both TNF and IL-17A blockers are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.
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February 2021

Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases.

RMD Open 2021 02;7(1)

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

In view of the COVID-19 pandemic, there is an unmet clinical need for the guidelines on vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). This position paper summarises the current data on COVID-19 infection in patients with AIIRD and development of vaccines against COVID-19, discusses the aspects of efficacy and safety of vaccination, and proposes preliminary considerations on vaccination against COVID-19 in patients with AIIRD, mainly based on the expert opinion and knowledge on the use of other vaccines in this population of patients.
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http://dx.doi.org/10.1136/rmdopen-2021-001594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907831PMC
February 2021

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

J Rheumatol 2021 Jul 15;48(7):1014-1021. Epub 2021 Jan 15.

V. Furer, MD, D. Levartovsky, MD, J. Wollman, MD, I. Wigler, MD, D. Paran, MD, I. Kaufman, MD, O. Elalouf, MD, S. Borok, MD, M. Anouk, MD, H. Sarbagil-Maman, MD, M. Berman, MD, A. Polachek, MD, O. Elkayam, MD, Department of Rheumatology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv.

Objective: To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs).

Methods: This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis.

Results: Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively.

Conclusion: The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.
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http://dx.doi.org/10.3899/jrheum.200961DOI Listing
July 2021

Dermal Filler Injections in Patients With Autoimmune and Inflammatory Rheumatic Diseases-The Patients' Perspective.

Dermatol Surg 2020 Dec 15;Publish Ahead of Print. Epub 2020 Dec 15.

Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Background: Injecting dermal fillers in patients with autoimmune inflammatory rheumatic diseases (AIIRDs) is controversial.

Objective: To evaluate the attitudes of patients with AIIRDs regarding the use of dermal fillers and the side effects of those who underwent them.

Methods: Patients with AIIRDs who attended a rheumatology outpatient clinic between 2016 and 2018 filled in a questionnaire about their attitudes toward dermal filler injections. The questionnaire evaluated information received from professionals and the factors that influenced their decision of whether or not to undergo the procedures.

Results: Overall, 194 patients with AIIRDs (mean age 56.5 ± 14.0, 99% women) responded. Forty-two of them had previously undergone the injections and intended to repeat them (Group A), 37 had not received filler injections but intended to do so (Group B), and 114 who had never undergone them did not intend to undergo them. The major motivation for undergoing filler injections was social. Patients treated with dermal fillers refrained from informing their rheumatologist about their injections. They were, however, highly satisfied with the procedure and reported negligible side effects.

Conclusion: The use of dermal fillers was apparently safe and well received by patients with AIIRDs. Physicians' recommendations to refrain from injecting them with dermal fillers should be reconsidered and evaluated in clinical studies.
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http://dx.doi.org/10.1097/DSS.0000000000002888DOI Listing
December 2020

The Diagnosis and Treatment of Adult Patients with SAPHO Syndrome: Controversies Revealed in a Multidisciplinary International Survey of Physicians.

Rheumatol Ther 2020 Dec 24;7(4):883-891. Epub 2020 Sep 24.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Introduction: This study aimed to investigate the current practice in the diagnosis and treatment of SAPHO syndrome among the international rheumatology and dermatology communities.

Methods: We conducted an electronic survey among the members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the Japan Spondyloarthritis, and Israeli Societies of Rheumatology.

Results: A total of 78 physicians participated in the survey: rheumatologists (83%, n = 65), dermatologists (11.5%, n = 9), and orthopedics (3.8%, n = 3). SAPHO was considered a subtype of spondyloarthritis by 48.7% (n = 38), a subtype of psoriatic arthritis by 19.2% (n = 15), a separate entity by 25.6% (n = 20), and a subtype of reactive arthritis by 6.4% (n = 5). Palmoplantar pustulosis was the most prevalent cutaneous manifestation (n = 44, 56.4%) and anterior chest pain-the most prevalent osteoarticular manifestation (n = 66, 84.6%). The majority (84.6%, n = 66) voted for the update of the present diagnostic criteria by Khan 1994. Magnetic resonance imaging was considered the preferred imaging modality for the diagnosis of SAPHO by 41% (n = 32). Conduction of bone biopsy for diagnosis of non-infectious osteitis was supported only by 10.3% (n = 8). Patient-reported outcomes were considered the most appropriate measure for the assessment of disease activity by 47.4% (n = 37). The treatment approach was overall similar among the rheumatology and dermatology communities, including non-steroidal anti-inflammatory drugs, bisphosphonates, conventional disease-modifying anti-inflammatory drugs, and biologics.

Conclusions: Our study underlines the controversy on diagnosis and treatment of SAPHO syndrome among specialists in rheumatology and dermatology and emphasizes an unmet need for update and validation of diagnostic criteria and treatment approach.
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http://dx.doi.org/10.1007/s40744-020-00235-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695776PMC
December 2020

Low-Dose Colchicine after Myocardial Infarction.

N Engl J Med 2020 04;382(17):1666-1667

Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

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http://dx.doi.org/10.1056/NEJMc2001194DOI Listing
April 2020

Immunogenicity and safety of vaccination against seasonal influenza vaccine in patients with psoriatic arthritis treated with secukinumab.

Vaccine 2020 01 22;38(4):847-851. Epub 2019 Nov 22.

Department of Rheumatology, Tel Aviv Medical Center, Israel; The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Objective: To assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) patients treated with secukinumab versus healthy controls (HC).

Methods: PsA patients administered secukinumab for ≥3 months and HC received the Sanofi Pasteur vaccine composed of 3 antigens (H3N3, H1N1, and B) and underwent clinical and laboratory assessments on the day of vaccination and 4-6 weeks later. Immunogenicity of the vaccine was evaluated by hemagglutination inhibition assay against those 3 antigens. Responders to each antigen were defined by a 4-fold increase in the antigen titer or by seroconversion in patients whose baseline level was <1/40.

Results: Thirty-two consecutive PsA patients treated with secukinumab for ≥3 months comprised the study group, 10 of whom received concomitant conventional synthetic disease-modifying drugs, mostly methotrexate. There were 17 age- and gender-matched HC (median age 48.5 years, 6 females). The geometric mean titers of each antigen increased significantly in both groups. The number of responders in each group was similar for H3N2 and H1N1, and significantly higher for B/Brisbane in the PsA group. The proportion of patients with a seroprotective level (a titer >1/40) was high and similar in both groups. There was no correlation between the response rate and age, gender, or selected parameters of disease activity (tender/swollen joint counts, Leeds enthesitis index, physician and patient global assessment, psoriasis area severity index, and C-reactive protein). No disease exacerbation was observed following the vaccination. No serious adverse effects were observed in both groups during the study period.

Conclusion: Secukinumab treatment does not affect the humoral response to influenza vaccine of patients with PsA.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.081DOI Listing
January 2020

Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD.

RMD Open 2019 19;5(2):e001041. Epub 2019 Sep 19.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objectives: The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available.

Methods: A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate.

Results: Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively.

Conclusion: Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.
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http://dx.doi.org/10.1136/rmdopen-2019-001041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803008PMC
April 2020

Prevalence of high-sensitivity cardiac troponin T in real-life cohorts of psoriatic arthritis and general population: a cross-sectional study.

Rheumatol Int 2020 Mar 23;40(3):437-444. Epub 2019 Oct 23.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann St, Tel Aviv, Israel.

Patients with psoriatic arthritis (PsA) are at increased risk of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) is a novel biomarker of CVD. The objective of this study is to determine the prevalence of circulating hs-cTnT in patients with PsA compared to the general population and to characterize a PsA subset with detectable hs-cTnT. A cross-sectional analysis of serum hs-cTnT levels was performed in 116 consecutive patients with PsA and the Tel-Aviv Medical Center Inflammatory Survey cohort of the general population (n = 6052) as a control group. The level and prevalence of hs-cTnT (ng/L) were similar in the entire study population: 4.94 ± 4.4, 30.2% in PsA, 5.17 ± 6.7, 34.2% and 5.38 ± 4.3, 37.9% in unmatched and matched control groups according to age, gender and cardiovascular risk factors, respectively. Factors associated with detectable hs-cTnT in PsA included male gender (p = 0.002), age (p = 0.007), hypertension (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.001). Axial disease, present in 25% of patients with PsA, was significantly associated with detectable hs-cTnT (p = 0.004). This association remained significant after adjusting for age, gender and traditional cardiovascular risk factors. No correlation between hs-cTnT levels and disease characteristics, PsA activity indices, C-reactive protein levels, or treatments for PsA was found. In summary, serum hs-cTnT was detectable in about the third of the PsA and control cohorts. In PsA, axial disease was significantly associated with detectable hs-TnT, warranting a particular attention to cardiovascular risk assessment in this sub-group. The role of hs-cTnT as a biomarker for CVD in PsA should be further investigated in prospective studies.
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http://dx.doi.org/10.1007/s00296-019-04461-yDOI Listing
March 2020

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations.

RMD Open 2019 9;5(2):e001035. Epub 2019 Sep 9.

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Aim: To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations.

Methods: An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018).

Results: While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved.

Conclusion: Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.
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http://dx.doi.org/10.1136/rmdopen-2019-001035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744079PMC
April 2020

2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.

Ann Rheum Dis 2020 01 14;79(1):39-52. Epub 2019 Aug 14.

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
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http://dx.doi.org/10.1136/annrheumdis-2019-215882DOI Listing
January 2020

Elevated Levels of Eotaxin-2 in Serum of Fibromyalgia Patients.

Pain Res Manag 2018 13;2018:7257681. Epub 2018 May 13.

Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. . 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. . The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), =0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. . Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS.
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http://dx.doi.org/10.1155/2018/7257681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971249PMC
December 2018

GRAPPA Trainees Symposium 2017: A Report from the GRAPPA 2017 Annual Meeting.

J Rheumatol Suppl 2018 Jun;94:4-10

From the Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York; Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, New York, USA; Department of Dermatology, Division of Dermatology and Venereology, Geneva University Hospital; Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Amsterdam, the Netherlands, a trainees symposium was held. Rheumatology and dermatology trainees engaged in psoriasis or psoriatic arthritis research presented their work. This report briefly reviews 6 oral presentations and 25 posters presented at the meeting.
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http://dx.doi.org/10.3899/jrheum.180130DOI Listing
June 2018

Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment.

Curr Med Res Opin 2018 10 23;34(10):1777-1783. Epub 2018 Mar 23.

a Rheumatology Department, Tel-Aviv Medical Center and the Sackler School of Medicine , Tel-Aviv University , Israel.

Objectives: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers.

Methods: A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data.

Results: The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity - 100%, specificity - 75%) The statistical power obtained in the prospective study was .9.

Conclusion: The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.
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http://dx.doi.org/10.1080/03007995.2018.1443581DOI Listing
October 2018

The Effect of the Presence of Fibromyalgia on Common Clinical Disease Activity Indices in Patients with Psoriatic Arthritis: A Cross-sectional Study.

J Rheumatol 2016 09 1;43(9):1749-54. Epub 2016 Jun 1.

From the departments of Rheumatology and Dermatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.S. Brikman, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; V. Furer, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; J. Wollman, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; S. Borok, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; H. Matz, MD, Department of Dermatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; A. Polachek, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; O. Elalouf, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; A. Sharabi, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; I. Kaufman, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; D. Paran, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University; O. Elkayam, MD, Department of Rheumatology, Tel Aviv Sourasky Medical Center, the Sackler Faculty of Medicine, Tel Aviv University.

Objective: To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA).

Methods: Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores.

Results: The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 ± 1.92 and 27.53 ± 19.23, respectively) than in patients with PsA only (4.25 ± 3.14 and 12.82 ± 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM.

Conclusion: Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment.
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http://dx.doi.org/10.3899/jrheum.151491DOI Listing
September 2016

Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs.

Semin Arthritis Rheum 2014 Feb 5;43(4):489-97. Epub 2013 Sep 5.

Clinical Trials Unit, Division of Rheumatology, New York University School of Medicine, New York, NY.

Objective: There is little information comparing the potential risk of cancer across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus of most contemporary pharmacoepidemiologic studies of cancer.

Methods: We conducted a comparative effectiveness study with cancer as the outcome. A large observational cohort of RA was followed up from 2001 to 2010. Reports of any cancer prompted a confirmation process that included adjudication of the primary cancer records. We used a propensity score (PS) with relevant covariates and cohort trimming to improve the balance between DMARD cohorts. Cox proportional hazard regression models were constructed to estimate the risk of cancer with various DMARDs, all compared with methotrexate.

Results: We identified 6806 DMARD courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408 abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05-0.65) and TNF antagonists (HR 0.29, 95% CI 0.05-0.65) were associated with a reduced adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI 0.40-5.97) and rituximab (HR 0.42, 95% CI 0.07-2.60) were similar in risk of cancer with methotrexate. These results were robust to sensitivity analyses. After controlling for DMARD exposures, risk factors for cancer included male gender, age, and alcohol consumption.

Conclusions: Cancer risk was elevated for methotrexate users compared with nbDMARDs and TNF antagonists.
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http://dx.doi.org/10.1016/j.semarthrit.2013.08.003DOI Listing
February 2014

Malignancy validation in a United States registry of rheumatoid arthritis patients.

BMC Musculoskelet Disord 2012 May 31;13:85. Epub 2012 May 31.

Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA.

Background: Physician reporting is commonly used to ascertain adverse events or outcomes measured in epidemiologic studies. However, little is known on the accuracy of physician reported malignancies compared to pertinent medical record review in large cohort studies.

Methods: The Consortium of Rheumatology Researchers of North America (CORRONA) registry gathers physician-completed questionnaires for rheumatoid arthritis (RA) patients, including request for information on incident malignancies, approximately every three months. For incident malignancies reported from October 1st, 2001, through December 31st, 2007, we retrospectively requested completion of a Targeted Adverse Event (TAE) form for additional information as well as primary source documents to adjudicate the malignancy reports. CORRONA has employed a prospective request for source documentation for these events since 2008. We classified each malignancy as definite, probable, possible, or not a malignancy.

Results: From 20,837 RA patients enrolled in CORRONA, 461 incident malignancies were initially reported on physician questionnaires. After review of returned source documents with adjudication, 234 were deemed definite, 69 probable, 101 possible, and 57 not an incident malignancy. The positive predictive value (PPV) of initial physician report of a malignancy versus "definite or probable" malignancy based on adjudication was 0.66 (95% CI 0.61 - 0.70). The PPV was 0.68 (95% CI 0.63 - 0.72) when the subsequent TAE form also confirmed the presence of malignancy. When possible malignancies were included, the PPV of physician-reported malignancies without a subsequent TAE form increased to 0.86 (0.83 - 0.89), and with a subsequent TAE form, 0.89 (0.85-0.91).

Conclusion: Twelve percent of initial physician reports of incident malignancy could not be confirmed with review of source documents. The most common reason for lack of confirmation was inability to obtain documents or insufficient data in source materials. These results suggest that timely collection of relevant medical records and an adjudication process are required to improve the accuracy of cancer reporting in epidemiologic studies.
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http://dx.doi.org/10.1186/1471-2474-13-85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403943PMC
May 2012

Polydactyly in a patient with a cardiovascular anomaly.

J Clin Rheumatol 2012 Jan;18(1):54-5

Division of Rheumatology, Department of Medicine, NYU Langone Medical Center-Hospital for Joint Diseases, New York, NY 10003, USA.

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http://dx.doi.org/10.1097/RHU.0b013e31823efff9DOI Listing
January 2012

Cardiovascular safety of biologic therapies for the treatment of RA.

Nat Rev Rheumatol 2011 Nov 15;8(1):13-21. Epub 2011 Nov 15.

Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, Suite 1410, New York, NY 10003, USA. [email protected] nyumc.org

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.
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http://dx.doi.org/10.1038/nrrheum.2011.168DOI Listing
November 2011

Noninvasive cardiovascular imaging in rheumatoid arthritis: current modalities and the emerging role of magnetic resonance and positron emission tomography imaging.

Semin Arthritis Rheum 2012 Apr 13;41(5):676-88. Epub 2011 Oct 13.

Division of Rheumatology, New York University Hospital for Joint Diseases, New York, New York 10003, USA.

Objectives: Rheumatoid arthritis (RA) is associated with premature atherosclerosis and increased prevalence of cardiovascular disease. The objective of this review is to summarize current and emerging imaging modalities for the evaluation of subclinical atherosclerosis in RA, with an emphasis on potential application of novel modalities, high-resolution magnetic resonance imaging and positron emission tomography, as screening tools for early cardiovascular disease risk stratification.

Methods: A PubMed literature search was undertaken using the search terms "rheumatoid arthritis" AND "cardiovascular disease" OR "atherosclerosis" OR "plaque" and including all relevant terms for imaging modalities.

Results: Two noninvasive imaging modalities have been widely adopted for direct visualization of arterial wall: carotid ultrasonography and cardiac computed tomography. Published studies in the RA population using these 2 modalities are reviewed. Novel cardiovascular imaging modalities are described, with an emphasis on high-resolution magnetic resonance imaging and positron emission tomography. Emerging research tools in vascular imaging, including dynamic and cardiac stress perfusion contrast-enhanced magnetic resonance imaging, are presented. The incremental imaging capabilities to characterize plaque composition and vessel wall inflammation as well myocardial abnormalities and published studies are systematically reviewed.

Conclusions: An increasing number of cardiovascular imaging modalities with improved characterization of features associated with plaque vulnerability have been developed. Given the heightened cardiovascular risk profile of the RA population, these novel imaging modalities offer promise for risk stratification and drug safety evaluation.
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http://dx.doi.org/10.1016/j.semarthrit.2011.08.007DOI Listing
April 2012

Absence of leukocytosis in bacteraemic pneumococcal pneumonia.

Prim Care Respir J 2011 Sep;20(3):276-81

Department of Internal Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.

Background: Evaluation of patients with respiratory symptoms in primary care medicine is often based on peripheral WBC count that dictates the extent of diagnostic investigation. A normal WBC count may result in a limited investigation, often omitting chest radiography.

Aims: To determine the extent to which patients hospitalised with bacteraemic pneumococcal pneumonia have no leukocytosis at presentation.

Methods: A retrospective analysis was performed of patients with bacteraemic community-acquired pneumococcal pneumonia from 2000 to 2007 in a community care academic medical centre. Records were reviewed for symptoms, signs, and laboratory data including pneumococcal serotypes, chest radiographs on admission, and outcome.

Results: 21% of the patients presented with a normal WBC count (16.7% of the children and 25.6% of the adults). Among this population with a normal WBC count at presentation, 90% of the adults and 70% of the children developed leukocytosis within a few days after admission.

Conclusions: In this study, in as many as one-fifth of all the patients with bacteraemic pneumococcal pneumonia, there was no leukocytosis at presentation. We therefore suggest that every patient with clinically suspected pneumonia should undergo chest radiography even if the WBC count is normal.
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http://dx.doi.org/10.4104/pcrj.2011.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549842PMC
September 2011
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