BackgroundTocilizumab (TCZ) is a humanized anti-IL-6 receptor-blocking monoclonal antibody used for the treatment of rheumatoid arthritis (RA), idiopathic juvenile arthritis (IJA) and off-label in Adult Onset Still Disease (AOSD). The development of anti-TCZ antibodies could reduce treatment efficacy or induce treatment failure.ObjectivesTo analyse TCZ serum levels and antidrug antibodies (ADA) in a cohort of RA, IJA and AOSD patients treated with TCZ, and to evaluate its relationship with Disease Activity Score using a 28-joint count (DAS28), C-reactive protein (CRP) levels and the presence of combined treatment with glucocorticoids or DMARDs.MethodsCross-section study including all patients undergoing chronic treatment with TCZ in a tertiary academic hospital. Referral area: 850,000 inhabitants. Twenty-two patients were included. TCZ serum and ADA levels were measured by ELISA (Theradiag) at baseline (before infusion), 15 days and 30 days after infusion.ResultsTwenty-two patients were studied: 18 RA, 3 IJA and 1 AOSD, 81.8% female; mean age and mean disease duration: 54.2 (±13) and 15.5 (±12) years respectively; 73% of the RA patients were positive for anti-CCP and 70% for rheumatoid factor, mean DAS28-CRP at day 0 and 30: 2.9 and 2.6 respectively. Fifteen patients were treated with TCZ for more than 1 year (range 12-58 months), 19 were treated with TCZ at 8 mg/kg, 2 at 6mg/kg, and one at 5mg/kg every 4 weeks due to low disease activity. Thirteen patients received TCZ in monotherapy, 9 received DMARDs combined treatment, 10 with glucocorticoids (mean dose 4mg/day, range 2-10mg). TCZ serum levels were at baseline: 1.2- 61.7 μg/ml, 15 days: <1-130.1 μg/ml and 30 days: <1-97.1 μg/ml. No patient showed presence of ADA. No correlation was found with DAS28-CRP, but there was inversely relation between CRP and TCZ serum levels (p=ns). The mean CRP levels were 14.4, 64.2 and 17.6 mg/dL at day 0, 15 and 30. TCZ Serum levels were higher in patients with combined therapy with DMARDs than those with monotherapy at day 15 and 30 (p=ns, 71 vs 55 μg/mL/23 vs 12 μg/mL, respectively). Patients treated without glucocorticoids had high levels of TCZ (68.62 vs 59.96 μg/mL at day 15 and 20.2 vs 13.68 μg/mL at day 30, p=ns)ConclusionsLevels of TZC were heterogeneous. Our patients showed no presence of ADA, this data suggest that TCZ has a low immunogenic potential. No correlation was found in disease activity and TCZ serum levels, but we found a relation with CRP levels. Patients with DAMRDs or without glucocorticoids showed higher levels of TCZ. We did not find correlation between combined treatment with DMARDs or glucocorticoids and levels of TCZ. Our study was limited due to a low sample size; we cannot exclude the correlation between TCZ and DAS28-CRP in a higher sample of patients.ReferencesDougados M, Kissel K, Conaghan PG et al. Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment strategies in rheumatoid arthritis: the ACT-RAY study. Ann Rheum Dis. 2014;73(5):803-9Van Herwaarden N, Herfke...

Objectives To describe the clinical characteristics, treatment and outcome of patients diagnosed with pyogenic septic arthritis. Methods Design: retrospective (1984-2012). Location: University hospital. Referial area: 800,000 inhabitants. The medical records of patients with pyogenic arthritis were reviewed. Inclusion criteria: isolation of bacteria in joint fluid or blood. Patients with soft tissue infection, prosthetic, fungal and mycobacterial septic arthritis were excluded. Results One hundred one patients were selected: 66 males and 35 females. Mean age: 54.5 ± 21.2 years. The following risk factors were identified: alcoholism (24), cirrhosis (12), diabetes mellitus (18), chronic renal failure (17), neutropenia (6), immunosuppression (10), HIV (10), AIDS (5), parenteral drug addiction (12), cancer (6), RA (4) and microcrystalline arthritis (17). Seventeen patients had undergone joint manipulation prior to the onset of the infection: 9 arthrocentesis with corticosteroids injection, 6 arthrocentesis and 2 arthroscopies. The pattern of join involvement was monoarticular in 72 patients (71.3%): knee 38 (36.8%), and shoulder and ankle 8 (8%) respectively. Polyarticular involvement was found in 29 patients (28.7%). Fifty nine patients 58.4% had fever. Cellulitis was observed in 17 cases (17%). The mean time between onset of symptoms and diagnosis was 7.9 ± 8.2 days. Mean hospital stay was 30.4 ± 28 days. Blood cultures were positive in 40 cases (39.7%) and in 85% of them the same microorganism was isolated in joint fluid. Septic arthritis was caused by gram positive in 79%, gram negative 19% and 2% were polymicrobial. The most common were: S. aureus methicillin sensitive (45), S. aureus methicillin resistant (MRSA in 5 cases since 2008), S. agalactiae (6), S. pyogenes (3), S. pneumoniae (9), E.Coli (9), P.aeuriginosa (3), Enterobacter cloacae (2) and Salmonella (2). Acute phase reactants were increased: ESR: 89.5 ± 29.6 mm/1sth and C-reactive protein 162 ± 122 mg/dl. The mean leukocyte count of joint fluid was 65,602 ± 62477/mm3. Synovial glucose was decreased in 50% of patients. Mean duration of intravenous antibiotic therapy: 3 weeks. Thirty-four patients (33.6%) required surgical treatment. Three patients required a second arthrotomy. Complications were: septic shock (20), pneumonia (6), reflex sympathetic dystrophy (2), osteonecrosis (2), endocarditis (3), respiratory distress (1). Most of the cases evolved favorably. Fifteen cases resulted in death (15%): 8 cases had monoarticular involvement and 7, polyarticular involvement. The causative organisms were: S. Aureus (10 cases), MRSA (3 cases), Pneumococcal (1 case) and polymicrobial (1 case of S.aureus more E.Coli). Conclusions S. aureus is the most common pathogen isolated. Furthermore MARSA is an emerging microorganism. Hematogenous spread and polyarticular involvement are poor prognostic factors. Prolonged antibiotic therapy and surgical debridement are essential for proper healing. Disclosure of Interest None Declared

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