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N Kappelmann, G Lewis, R Dantzer, P B Jones, G M Khandaker
Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials...
October 18, 2016: Molecular Psychiatry
Emire Seyahi
PURPOSE OF REVIEW: Takayasu arteritis has long been considered as an uncommon disease, rather specific to the Far-East; however recent surveys show that the disease can be seen in all ethnicities around the world with increasing prevalence rates. Nowadays, it would not be fair to consider Takayasu arteritis as a rare disease. RECENT FINDINGS: Although involvement of the thoracic aorta and its branches was more common among females, males had a tendency toward limited involvement of the abdominal aorta and its branches...
September 29, 2016: Current Opinion in Rheumatology
Alan Kivitz, Thomas Wallace, Ewa Olech, Michael Borofsky, Jenny Devenport, Jinglan Pei, Margaret Michalska
INTRODUCTION: To assess the long-term safety and efficacy of subcutaneous tocilizumab (TCZ-SC) in US patients with rheumatoid arthritis (RA) who rolled over from the two global phase 3 studies, SUMMACTA (NCT01194414) and BREVACTA (NCT1232569), into this open-label, single-arm, phase 3b study. METHODS: Patients continued to receive TCZ-SC 162 mg weekly or every other week or switched from intravenous TCZ to TCZ-SC 162 mg qw for up to 84 weeks. The primary endpoint was the proportion of patients with serious adverse events (SAEs)...
September 24, 2016: Rheumatol Ther
Sharareh Monemi, Erhan Berber, Khaled Sarsour, Jianmei Wang, Kathy Lampl, Kamal Bharucha, Attila Pethoe-Schramm
INTRODUCTION: The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA). METHODS: Reporting rates of GIP events were estimated from three distinct patient data sets: a TCZ-IV RA clinical trial all-exposure population, a global TCZ postmarketing safety database population, and a US healthcare claims database population of patients with RA, including patients who received TCZ, anti-tumor necrosis factor (aTNF) agents, or abatacept...
July 15, 2016: Rheumatol Ther
Dimitrios A Pappas, Ani John, Jeffrey R Curtis, George W Reed, Chitra Karki, Robert Magner, Joel M Kremer, Ashwini Shewade, Jeffrey D Greenberg
INTRODUCTION: In the United States, the recommended starting dose of intravenous tocilizumab (TCZ) is 4 mg/kg every 4 weeks, with an increase to 8 mg/kg based on clinical response for patients with moderate to severe rheumatoid arthritis; however, data on how TCZ dose is escalated in real life are missing. The objective of this analysis was to describe patterns of early intravenous TCZ dose escalation in a real-world setting using data from the Corrona registry. METHODS: All patients enrolled in the comparative effectiveness substudy (CERTAIN) nested within Corrona who initiated TCZ and completed 3- and 6-month study visits were eligible for inclusion...
June 2016: Rheumatol Ther
Paul Welsh, Katie Tuckwell, Iain B McInnes, Naveed Sattar
BACKGROUND AND AIMS: Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients. METHODS: A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial...
October 8, 2016: Atherosclerosis
Kazuhiko Kotani, Michiaki Miyamoto, Hitoshi Ando
Rheumatoid arthritis (RA) is a chronic inflammatory disease with a potential cardiovascular (CV) risk. Flow-mediated vasodilation (FMD) is an ultrasonic method to evaluate endothelial function. RA is a contributor to endothelial dysfunction, a CV risk. Relevant insights on the improvement of the CV outcomes in RA patients may be obtained by a systematic review of trials that investigated the effects of RA treatment on FMD in RA patients. This review found that treatments with antirheumatic drugs and some non-antirheumatic drugs could improve the FMD in RA patients...
October 13, 2016: Current Vascular Pharmacology
Natalia Cabrera, Agnes Duquesne, Marine Desjonquères, Jean-Paul Larbre, Jean-Christophe Lega, Nicole Fabien, Alexandre Belot
Arthritis is one of the main manifestations of mixed connective tissue disease (MCTD) and overlap syndrome in children and can be responsible for functional disability. We report on 2 children with arthritis that were dramatically improved by a treatment with interleukin-6 (IL-6) blockers in the context of connective tissue disease. However, in both cases, other systemic autoimmune symptoms were not modified by the treatment and autoantibodies tend to increase, suggesting a differential effect of IL-6 inhibition on articular inflammation and systemic autoimmunity...
2016: RMD Open
Yuichiro Matsuoka, Hideki Nakayama, Ryoji Yoshida, Akiyuki Hirosue, Masashi Nagata, Takuya Tanaka, Kenta Kawahara, Junki Sakata, Hidetaka Arita, Hikaru Nakashima, Satoru Shinriki, Daiki Fukuma, Hidenao Ogi, Akimitsu Hiraki, Masanori Shinohara, Ryo Toya, Ryuji Murakami
BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. METHODS: Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro...
October 13, 2016: British Journal of Cancer
Andrea Picchianti Diamanti, Milica Markovic, Giuseppe Argento, Simonetta Giovagnoli, Alberto Ricci, Bruno Laganà, Raffaele D'Amelio
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that can present different extrarticular manifestations involving heart, lungs and kidneys. In recent years there has been a growing awareness of the central role played by the lungs in the onset and progression of RA. In particular interstitial lung disease (ILD) is a common pulmonary manifestation that may be related to the inflammatory process itself, infectious complications and to the treatments used. Management of patients with ILD/RA is still a challenge for clinicians, both synthetic [mainly methotrexate (MTX), leflunomide] and biologic immunosuppressors [mainly anti-tumor necrosis factor (TNF)α] have in fact been related to the onset or worsening of lung diseases with conflicting data...
October 12, 2016: Therapeutic Advances in Respiratory Disease
Vanesa Calvo-Río, Ricardo Blanco, Montserrat Santos-Gómez, David Díaz-Valle, Esperanza Pato, Javier Loricera, María C González-Vela, Rosalía Demetrio-Pablo, José L Hernández, Miguel A González-Gay
PURPOSE: To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR). METHODS: Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy. RESULTS: Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab...
October 11, 2016: Ocular Immunology and Inflammation
Rafael Alfonso-Cristancho, Nigel Armstrong, Ramesh Arjunji, Rob Riemsma, Gill Worthy, Rita Ganguly, Jos Kleijnen
Our aim was to establish the comparative effectiveness of rheumatoid arthritis (RA) biologics, using a systematic review and network meta-analysis. The systematic review used randomized controlled trials (RCTs) in adults with RA who failed treatment with conventional disease-modifying agents for rheumatoid disease (cDMARDs). We compared the effectiveness of abatacept, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, and rituximab to tocilizumab, a recent biologic with a different mechanism of action (anti-IL-6 receptor)...
October 10, 2016: Clinical Rheumatology
Eun Bong Lee, Nikki Daskalakis, Christine Xu, Anne Paccaly, Barry Miller, Roy Fleischmann, Inga Bodrug, Alan Kivitz
INTRODUCTION: Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction...
October 8, 2016: Clinical Pharmacokinetics
Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Giacomo Maria Guidelli, Enrico Selvi, Maurizio Acampa, Franco Laghi-Pasini
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease primarily affecting synovial joints and is characterized by persistent high-grade systemic inflammation. Proinflammatory cytokines, particularly interleukin-6 (IL-6), are of crucial importance in the pathogenesis of the disease, driving both joint inflammation and extra-articular comorbidities. Tocilizumab, a humanized IL-6 receptor-inhibiting monoclonal antibody, has been the first, and, to date, the only, IL-6 inhibitor approved for the treatment of RA...
2016: Drug Design, Development and Therapy
Yuan An, Tian Liu, Dongyi He, Lijun Wu, Juan Li, Yi Liu, Liqi Bi, Bin Zhou, Changsong Lin, Lan He, Xiangyuan Liu, Xiaofeng Li, Niansheng Yang, Zhuoli Zhang, Hui Song, Wei Wei, Jing Liu, Yu Bi, Zhanguo Li
The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10...
October 5, 2016: Clinical Rheumatology
Ömer Karadağ, Timuçin Kaşifoğlu, Birol Özer, Sabahattin Kaymakoğlu, Yeşim Kuş, Murat İnanç, Gökhan Keser, Sedat Kiraz
Biological drugs (tumor necrosis factor inhibitors, rituximab, tocilizumab, abatacept, and tofacitinib) are important treatment alternatives in rheumatology, particularly for resistant patients. However, they may cause hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation; for instance, HBV reactivation may occur in a patient who is an inactive hepatitis B surface antigen (HBsAg) carrier or who has resolved HBV infection. Therefore, the screening of patients before biological treatment and the application of a prophylactic treatment, particularly with respect to latent HBV infections, are recommended when necessary...
March 2016: Eur J Rheumatol
Mark Wunderlich, Courtney Stockman, Mahima Devarajan, Navin Ravishankar, Christina Sexton, Ashish R Kumar, Benjamin Mizukawa, James C Mulloy
Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6...
September 22, 2016: JCI Insight
Vanesa Calvo-Río, Montserrat Santos-Gómez, Inmaculada Calvo, Ma Isabel González-Fernández, Berta López Montesinos, Marina Mesquida, Alfredo Adán, María Victoria Hernández, Olga Maíz, Antonio Atanes, Beatriz Bravo, Consuelo Modesto, Gisela Díaz-Cordovés, Natalia Palmou-Fontana, Javier Loricera, M C González-Vela, Rosalía Demetrio-Pablo, J L Hernández, Miguel A González-Gay, Ricardo Blanco
OBJECTIVE: To assess the efficacy of Tocilizumab (TCZ) for Juvenile Idiopathic Arthritis (JIA)-associated uveitis. METHODS: Multicenter study of patients with JIA-associated uveitis refractory to conventional immunosuppressive drugs and anti-TNFα agents. RESULTS: We assessed 25 (21 women) patients (47 affected eyes); mean age 18.5±8.3 years. Uveitis was bilateral in 22. Cystoid macular edema (CME) was present in 9 patients. Ocular sequelae found at TCZ onset included: cataracts (13), glaucoma (7), synechiae (10), band keratopathy (12), maculopathy (9), and amblyopia (5)...
October 1, 2016: Arthritis & Rheumatology
Satoshi Suzuki, Souichiro Nakano, Seiichiro Ando, Ran Matsudaira, Yoshinori Kanai, Kenjiro Yamanaka, Yoshinari Takasaki
Anemia often develops in rheumatoid arthritis (RA) patients. In the present study, we examined the association between the therapeutic effectiveness of the biologic agent tocilizumab (TCZ) and potential predictors of therapeutic effectiveness. We focused on the amelioration of anemia of chronic inflammation through the mechanism of direct inhibition of Interleukin (IL)-6 receptor-mediated signals by TCZ. Serum hepcidin-25, which is expressed in an IL-6 dependent manner and is a major cause of anemia of chronic inflammation, was measured in 10 RA patients, before and after administration of TCZ...
September 17, 2016: Revista Brasileira de Reumatologia
Eri Watanabe, Hitoshi Sugawara, Takeshi Yamashita, Akira Ishii, Aya Oda, Chihiro Terai
We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia...
2016: Case Reports in Medicine
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