Bahar Artım Esen

Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: an open-label pilot study.

Objective Uveitis and retinal vasculitis are sight-threatening manifestations of Behçets disease with limited treatment options. This pilot study aimed to evaluate the safety, pharmacokinetics and clinical activity of XOMA 052 (gevokizumab), a recombinant humanised anti-interleukin 1β antibody, in Behçets disease patients with uveitis. Methods Patients with acute posterior or panuveitis, and/or retinal vasculitis, resistant to azathioprine and/or ciclosporin, and receiving 10 mg/day or less of prednisolone, were enrolled into the 98-day study. Immunosuppressive agents were discontinued at baseline. Patients received a single infusion of XOMA 052 (0.3 mg/kg). The safety and uveitis status and pharmacokinetics of XOMA 052 were evaluated. Results Seven patients enrolled and completed the study. No treatment-related adverse event was observed. XOMA 052 treatment was associated with rapid and durable clinical response in all patients. Complete resolution of intraocular inflammation was achieved in 4–21 days (median 14 days), with a median duration of response of 49 days (range 21–97 days); one patient remained exacerbation free throughout the study. Conclusions Well tolerated, XOMA 052 resulted in a rapid onset and sustained reduction in intraocular inflammation in patients with resistant uveitis and retinal vasculitis. Moreover, the effect was observed despite discontinuation of immunosuppressive agents and without the need to increase corticosteroid dosages.

SAT0489 Assesment of persistent organ damage according to imacs (INTERNATIONAL MYOSITIS ASSESMENT AND CLINICAL STUDIES) myositis damage index in 92 patients with idiopathic inflammatory myositis

Background Number of work regarding long term organ damage caused by idiopathic inflamatory myopathies (IIM) and risk factors associated with organ damage have been undrstudied and never reported from Turkey; recently a new tool as developed fort that purpose. Objectives In this study we aimed to evaluate by long term organ damage and risk factors, associated with these prospectively in IIM patients. Methods IIM patients (n=110) who has been followed up for at least six month by our clinic and fulfilling Bohan and Peter criteria were recruited. Demographic data, clinical and serological features, treatment and final clinical tatus was recorded. IMACS Miyositis Damage Index (MDI) was determined twice in 92 patients (71% female) at the time of diagnosis from the records and at the at last clinical visit prospectively. Results Mean age of the 92 patients during the diagnosis was 46±14.7. Out of 92 patients 69% had dermatomyositis, 23% had polymyositis, 8% had necrotizing autoimmune myopathy and inclusion body myositis. Mean follow up was 82 months. Frequencies of disphagia, respiratuary muscle involvement and intertstitial lung disease were 29;5;34% respectively. Twenty-one percent of the patients had associated malignancy. The mean daily prednisolone dosage and total amount was 7.5 mg/day and 9000 mgs. Mortality was 13%. Initial mean MDI at the time of diagnosis was 1.6±3.0 (range, 0–14) and the last DMI score recorded was 6.1±4.7 (range, 0–21). After the last assessment the proportion of patients without damage was 8% and whose score was 4 were 37%. The last DMI score was significantly higher than the first DMI score (p<0.001). The last DMI in females and patients with calcinosis were significantly high (p=0.002; p=0.007). The last DMI score and disease duration were weakly corelated (r=0.35 p=0.001). A moderately significant correlation was found between the last DMI score, the duration of glucocorticoid use and the total dose used (r=0.48 p<0.001; r=0.45 p<0.001). Conclusions Our long term follow up data showed that persistent organ damage assessed by DMI and mortality were high in patients with IIM and over half of patients developed severe damage. Organ damage was detected in some patients at presentation and DMI scores were significantly increased during the follow up. DMI scores were found high in females and in patients with calcinosis. There were significant correlation between disease duration, the duration of glucocorticoid use, the total dose used and DMI scores. Current treatments and strategies have been insufficient at improving the prognosis of patients with IIM and new treatment strategies and drugs are needed. Disclosure of Interest None declared

FRI0479 Efficacy of Colchicine and IL-1 Inhibitors in Amyloidosis Associated with Familial Mediterranean Fever: A Retrospective Analysis

Background Familial Mediterranean fever (FMF), the most common form of hereditary autoinflammatory diseases, is associated with increased risk for secondary (AA) amyloidosis Objectives We herein aimed to investigate the features of FMF patients with amyloidosis with respect to their responses to current therapies Methods We enrolled FMF patients with amyloidosis who were regularly followed-up for at least 6 months between 1978 and 2015 into the study. Starting times for colchicine, anakinra or canakinumab and treatment responses were noted. Proteinuria (spot urine protein/creatinine ratio) and C-reactive protein (CRP) levels were measured in every three months of follow-up. Partial response was defined as ≥50% decrease in baseline proteinuria accompanied by a normal serum creatinine level, whereas complete response was defined as <0.3 gr/d baseline proteinuria and stable serum creatinine. Correlations between treatment responders and continuously elevated or normalized CRP levels were tested by using a chi-square test Results We identified 79 FMF patients with documented secondary amyloidosis, and all were on colchicine treatment. Their demographic features are shown in Table 1. Mean time to diagnosis after the first symptom was 10 years. Patients were evaluated for partial and complete response after mean follow-up period of 66±85 months. Response to colchicine was observed in 30/65 patients [partial response in 19 (29%), complete response in 11 (17%)]; and 54% was non-responder to colchicine. Anakinra was added to treatment in 22 patients with inadequate response to colchicine, which resulted in partial response in 12, and complete response in 2. Eight patients with partial response to colchicine also received anakinra for better control of attacks and/or elevated acute phase response, and a complete response was achieved in 3 patients. In 3 patients, anakinra was switched to canakinumab because of local injection site reaction (1 patient) and persistence of proteinuria (2 patients). Among those, two patients had partial response, and another underwent hemodialysis due to progressive kidney failure. No significant association was observed between normalized CRP levels and response to treatment with respect to proteinuria and creatinine levels (colchicine; p=0.67, anakinra/canakinumab;p=0.82). No serious infection requiring hospitalization was detected in association with IL-1 blockade.Table 1. Demographic features of FMF patients with amyloidosis Male/Female 40/39 Age of onset (mean ± SD, range) 16±12 (2–68) Age of diagnosis (mean ± SD, range) 27±13 (7–70) Family history of FMF 47% Disease follow-up duration (mo) 66±85 (6–480) Time to diagnosis (mo) 121±136 (2–576) Family history of amyloidosis (%) 18% Arthritis at presentation (%) 60% MEFV variations (n=46) M694V, 68% V726A, 10% M680I, 15% Others, 7% IL-1 inhibitors n (%) 43 (54%) Patients on hemodialysis 7 (9%) Renal Transplantation n (%) 17 (21%) High CRP levels in attack-free periods n (%) 31 (39%) Conclusions Amyloidosis still remains as an important complication of FMF, and a satisfactory response to colchicine could be observed in an important proportion of patients. Treatment with IL-1 inhibitors seems to be an effective and safe option for those patients with an inadequate response to colchicine Disclosure of Interest None declared