Emerging drugs for uveitis

Abstract

Importance of the Field Uveitis is a challenging disease covering both infectious and noninfectious conditions. The current treatment strategies are hampered by the paucity of randomized controlled trials (RCTs) and few trials comparing efficacy of different agents. Areas Covered in this Review This review describes the current and future treatments of uveitis. A literature search was performed in PUBMED from 1965 to 2010 on drugs treating ocular inflammation with emphasis placed on more recent, larger studies. What the Reader Will Gain Readers should gain a basic understanding of current treatment strategies beginning with corticosteroids and transitioning to steroid sparing agents. Steroid sparing agents include the antimetabolites which include methotrexate, azathioprine, and mycophenolate mofetil; the calcineurin inhibitors which include cyclosporine, tacrolimus; alkylating agents which include cyclophosphamide and chlorambucil; and biologics which include the TNF-α inhibitors infliximab, adalimumab, and etanercept; daclizumab, interferon α2a, and rituximab. Take Home Message Newer agents are typically formulated from existing drugs or developed based on new advances in immunology. Future treatment will require a better understanding of the mechanisms involved in autoimmune diseases and better delivery systems in order to provide targeted treatment with minimal side effects.

Modern Opportunities in Uveitis Treatment

“…Основные группы иммуносупрессивных препаратов представлены анкилирующими агентами, антиметабо-литами, ингибиторами Т-клеток и так называемыми био-логическими модуляторами иммунного ответа (biologic response modifiers или BRMs) [27,28,29].…”

“…К группе ингибиторов Т-клеток относят кальцинев-риновые ингибиторы циклоспорин и такролимус, ко-торые нарушают дифференцировку и пролиферацию Т-клеток [27,28,30].…”

“…Провоспалительные цитокины выполняют ключевую роль в возникновении и поддер-жании как острого, так и хронического воспаления [28,[33][34][35]. Одним из важнейших медиаторов воспаления и апоптоза является TNF-α (tumor necrosis factor-α -фак-тор некроза опухоли-α).…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…Examples of steroid antiinflammatory include prednisone and fluocinolone (Callanan et al 2008; The Multicenter Uveitis Steroid Treatment Trial Research et al 2011), and immunosuppressive agents include methotrexate, mycophenolate, azathioprine, and cyclosporine. In some cases, immune-specific biological response modifiers such as rituximab, abatacept, daclizumab, and the TNF-α inhibitors, infliximab and adalimumab, are also used (Larson et al 2011;Nussenblatt et al 1999;). Prednisone, a mixture of glucocorticoid and mineralocorticoid, would likely bind to both intracellular glucocorticoid (GR) and mineralocorticoid receptor (MR) complexes and control gene transcription via direct and indirect mechanisms.…”

“…While methotrexate is most commonly administered orally, it can also be given via subcutaneous or intravitreal injections. When given orally, up to 35% of the dose is metabolized by intestinal flora prior to absorption; however, when parenterally administered, it is fully absorbed (Gangaputra et al 2009;Larson et al 2011). Gangaputra and colleagues retrospectively reviewed the records of 384 patients identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Study and found no significant difference in the effectiveness of subcutaneous versus oral routes of administration (Gangaputra et al 2009).…”