Efficacy of TNF-α antagonist and other immunomodulators in the treatment of patients with ophthalmologic manifestations of Behcet's disease and HLA B51 positive vasculitis

Abstract

Bacground/Aim. Behcet's disease is genetically conditioned, immune-mediated multisystem occlusive vasculitis of small blood vessels, espesially venules, of unknown etiology. The aim of this study was to analyze the clinical features, disease activity and therapy of the patients with ophthalmologic manifestation of Behcet's disease. Methods. In this study symptoms and signs of the disease were analyzed both prospectively and retrospectively during the active manifestation of the disease. The diagnosis was reached according to the International Criteria for Behcet's Disease (2006). The treatment effects were evaluated based on the presence of the best corrected visual acuity and the inflammation of the vitreous humour before and after the application of our therapeutic method. The applied therapeutic modality consisted of the primary application of corticosteroid therapy in the active stage of the disease complemented with the choice of drugs from the immunosuppressive group. In this study there drugs were cyclosporine or methotrexate. A treatment refractory patients with poor vision prognosis were treated with a third drug, the biological preparation infliximab, a tumor necrosis factor-alpha (TNF-?) antagonist. Results. The mean age of 11 patients with ophthalmologic manifestation of Behcet's disease was 50.6 years. HLA B-5(51) was positive in 81% of the patients while 36% of the patients had positive pathergy test. Changes in affected eyes included vitritis (100%), posterior uveitis (45%), panuveitis (54%), retinal vasculitis (54%), cystoid macular edema (54%), and cystoid degeneration (18%). Increased intraocular pressure was observed in 27% of the patients. There was no statistically significant variation in disease activity parameters in any of the patients (p > 0.05). A statistically significant improvement in visual acuity (p < 0.05) and a high statistically significant decrease of inflammation of the worst affected eyes (p = 0.001) were detected. Conclusion. Our therapeutic method is useful for producing the optimal therapeutic plan for the acute - chronic stage of the difficult ophtamological manifestation of Behcet's desease as well as the prevention of relapse. However the high cost of the therapy and the potential complications should be taken into consideration when prescribing this therapy, especially a TNF-? antagonist.Uvod/Cilj. Behcetova bolest je genetski uslovljen, imunoloski posredovan multisistemski okluzivni vaskulitis malih krvnih sudova, posebno venula, nepoznate etiologije. Cilj rada bio je analiza elemenata klinicke slike, aktivnosti oboljenja kao i terapije bolesnika sa oftalmoloskom manifestacijom Behcetove bolesti. Metode. Ovom prospektivno-retrospektivnom studijom obuhvaceno je 11 bolesnika iz dva oftalmoloska klinicka centra, kojima je dijagnoza Behcetove bolesti postavljenja na osnovu Internacionalnih kriterijuma za Behcetovu bolest iz 2006 godine. Simptomi i znaci oboljenja ispitivani su prospektivno i retrospektivno u vreme aktivne manifestacije bolesti. Efekat terapije procenjivan je pracenjem najbolje korigovane vidne ostrine i inflamacije u staklastom telu pre i posle primene terapijskog modaliteta. Primenjena terapija sastojala se od primarne kortikosteroidne terapije u aktivnoj fazi bolesti koja je dopunjavana drugim lekom izbora iz grupe imunosupresiva. U nasem slucaju to je bio ciklosporin ili metotreksat. Refrakterni slucajevi sa losom vidnom prognozom leceni su i trecim lekom, bioloskim preparatom infliksimabom, TNF-? antagonistom. Rezultati. Prosecna starost 11 bolesnika sa Behcetovom bolesti bila je 50,6 godina. HLA B-5(51) tip bio je pozitivan kod 81% bolesnika, a pathergy test kod 36% bolesnika. Promene na oku bile su u vidu vitritsa (100%), zadnjeg uveitisa (45%), panuveitisa (54%), vaskulitisa retine (54%), cistoidnog edema makule (54%), cistoidne degeneracije makule (18%). Povisen intraokularni pritisak imalo je 27% bolesnika. Parametri aktivnosti bolesti nisu pokazali statisticki znacajno odstupanje kod ispitivanih bolesnika (p > 0,05). Uoceno je statisticki znacajno poboljsanje vidne ostrine (p < 0,05) losijeg oka nakon terapije. Takodje, utvrdjeno je statisticki visokoznacajno smanjenje inflamacije u losijem oku u ispitivanoj grupi bolesnika (p = 0,001). Zakljucak. Utvrdjeno je statisticki znacajno poboljsanje vidne ostrine i smanjenje inflamacije kod ispitivanih bolesnika primenom terapijskog protokola na bazi kortikosteroida, ciklosporina (metotreksata) ili TNF-? antagoniste. Visoka cena terapije i potencijalne komplikacije predstavljaju ogranicavajuce faktore za propisivanje TNF-? antagoniste.