Effects of anti-TNF biologic drugs on uveitis severity in Beh?et patients: systematic review and Meta-analysis

INTRODUCTION

Beh?et’s disease (BD) was first discovered by Hulusi Beh?et

. The geographical distribution of BD is related to the Silk Road rout. The disease is widespread in Middle Eastern,Far Eastern and Mediterranean countries such as Iran, Turkey,Tunisia, China, and Japan

. The highest incidence of BD is in Turkey (80 to 370 patients per 100 000 population). The prevalence of the disease in Japan is about 13.5 per 100 000 and in Iran 80 per 100 000

. It is a vasculitis associated with oral and genital ulcers, skin lesions and ocular involvement

.Ocular involvement is in the form of recurrent non-granulomatous uveitis that can affect the anterior and posterior chambers of the eye. Uveitis is usually bilateral

. However, the intestine and the central nervous system can also be affected

.

Management and treatment of BD is a serious challenge due to different clinical aspects. Therefore, treatment should be proportional to the patient’s condition and severity of clinical symptoms

. Colchicine and non-steroidal anti-inflammatory drugs are often used to treat joint and mucosal involvement.However, more aggressive methods and immune suppressive agents are needed to treat severe symptoms such as uveitis,retinal vasculitis, neurological and gastrointestinal involvement

.Current treatment focuses on reducing inflammation and controlling the immune system. For severe manifestation of the disease, high dose corticosteroids are used

.

第一，在招投標(biāo)階段，招標(biāo)單位要保證招標(biāo)程序合法公平，盡量選擇信譽度高、技術(shù)過硬、有實力且報價相對較低的建設(shè)施工單位，嚴(yán)禁通過不合理方式獲取工程承包權(quán)及濫用私權(quán)行為的出現(xiàn)。第二，在工程建設(shè)過程中，承包商要結(jié)合施工合同的各項條款，采取科學(xué)有效的施工進度管理措施，加強對分包事項等的監(jiān)督管理，同時監(jiān)理方要充分體現(xiàn)出自身的監(jiān)督職能作用，強化管理與控制，確保工程建設(shè)的順利開展。第三，在竣工驗收階段，要根據(jù)合同約定的工程數(shù)量與質(zhì)量，并結(jié)合相關(guān)標(biāo)準(zhǔn)進行驗收，確保工程質(zhì)量的合格，防止因質(zhì)量不合格出現(xiàn)返工，甚至安全危險因素等，進而影響工程按期交付使用情況的發(fā)生。

BD patients have high levels of proinflammatory cytokines such as IL-1, IL-2, IL-6, tumor necrosis factor (TNF-α), IL-12,IL-17, IL-18, and IL-23R

. TNF-α is an inflammatory cytokine that plays a role in homeostasis and immune response and in fact, it plays a major role in autoimmune diseases pathogenesis

. This cytokine is encoded in the class 3 region of the HLA complex adjacent to HLA-B

. TNF-α is secreted by many types of cells such as macrophages,monocytes and lymphocytes

. Anti-TNF drugs are a group of medications that suppresses the physiologic response to

隨著油田企業(yè)業(yè)務(wù)的開展，檔案資料的內(nèi)容也逐漸增加，給檔案管理工作帶來了更高的難度。此外，對于油田企業(yè)的檔案來說，不僅僅需要做好保存工作，而且要挖掘檔案的潛在價值，為當(dāng)前工作更高質(zhì)量、更高效率地開展提供必要的借鑒。而這些工作的開展，都離不開一套完善的檔案信息化管理制度。由于油田企業(yè)對于檔案管理工作重視不足，配套的信息化管理制度也沒有建立起來。有些企業(yè)即便是有檔案信息化數(shù)據(jù)運行管理制度，在實際工作中沒有嚴(yán)格執(zhí)行，管理制度形同虛設(shè)，檔案管理人員工作中存在較大的隨意性。

TNF-α. The medications in this class include infliximab,etanercept, adalimumab, certolizumab pegol and golimumab.Infliximab, adalimumab, and golimumab are monoclonal antibodies against TNF-α. Etanercept is a soluble, divalent TNF-α receptor that binds to TNF-α to prevent it from binding to its receptor on the cell. Certolizumab pegol is the antigenbinding fragment (Fab’) of a humanized monoclonal antibody that has been conjugated to polyethylene glycol. Induction of antibodies against TNF is largely dependent on its structure,chimeric drugs have a higher capacity to stimulate the immune system than human drugs

.

The essential purposes in the management of patients with Beh?et’s uveitis are fast elimination of visual inflammation,avoidance of recurrent attacks, getting of whole remission,and maintenance of vision. Corticosteroids are generally used for the treatment of episodes of inflammation; however, their long-term use is associated with unacceptable side effects.Relapses are normal in the setting of steroid mono-therapy,and conventional immunosuppressive drugs have usually been used for long-term treatment

.

The combination of azathioprine and cyclosporine is more impressive than is immunotherapy with either factor, or combination therapy is used as a severe immunosuppressive regimen for the treatment of patients with severe Beh?et’s uveitis

. In addition, we did not find any studies comparing infliximab with steroids. However, in some studies, infliximab was compared with cyclosporine, and the results showed that following the use of infliximab, the conditions of ocular inflammation were greatly reduced

.

Anti-TNF drugs that has been approved for treatment of rheumatoid arthritis, Crohn’s disease, and ankylosing spondylitis and has been used for the treatment of uveitis in BD with promising results

. In general, anti-TNFs such as infliximab have been used to treatment uveitis, and anti-TNFs such as etanercept have been used to treat skin lesions

. Some studies have suggested that long-term use of biologic drugs can lead to infection in some patients. However, some other studies have shown that no side effects lead to infection of the skin, soft tissues and joints

. In some other studies, it has been reported to cause cancer in people who have taken these drugs for a long time. But in general, none has been proven

.However, due to inconsistent results of the present studies and the lack of systematic study, this study is intended to evaluate the therapeutic effects of anti-TNF agents in BD patients with ocular involvement.

MATERIALS AND METHODS

After determining the search keywords,including Beh?et’s disease, Beh?et’s syndrome, adamantiades-Beh?et’s disease, anti-TNF agents and uveitis, they were searched both using MeSH keywords and freely in the databases of MEDLINE, Scopus, CINHAL, Psycoinfo,Cochrane Library, Proquest. Iranmedex, SID, IranDoc, Magiran databases were also searched for information in Persian. In addition to the above databases, the list of selected study resources as well as related conferences was searched manually.

早白堊世華北克拉通東部進入破壞峰期，淺部地質(zhì)以伸展活動為特征，廣泛出現(xiàn)斷陷盆地，而深部過程以巖石圈轉(zhuǎn)型與減薄為特征，主要表現(xiàn)形式為巖漿活動[18]。……