Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis.

Objective: Few studies have investigated the efficacy of subcutaneous tocilizumab (TCZ-SC) on ultrasound-detected inflammation. This study aimed to explore the clinical efficacy of TCZ-SC treatment in rheumatoid arthritis (RA) patients and to evaluate the response by ultrasound compared to Composite Disease Activity Scores (CDAS).Method: This open-label, single-arm study enrolled RA patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs initiating TCZ-SC 162 mg once weekly for 24 weeks, with clinical assessments at baseline, 2, 4, 8, 12, 16, 20, and 24 weeks. Ultrasound examinations [semi-quantitative score (0-3) of 36 joints and four tendons] were performed at baseline, 4, 12, and 24 weeks. CDAS and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) response, and sum scores of ultrasound grey scale/Doppler were calculated. Changes during follow-up were explored by the Mann-Whitney test and correlations by Spearman's rho.Results: In total, 133 patients (mean ± sd age 55.9 ± 12.0 years) were assessed clinically and 110 patients were also examined with ultrasound. All clinical and ultrasound scores decreased significantly after 4 weeks (p < 0.001). At 24 weeks there was EULAR good response in 87.7% and ACR 70% response in 47.4%. Ultrasound scores had no or low correlations with patient-reported outcomes. At 24 weeks, CDAS remission was achieved in 27.4-83.5% and a sum score Doppler of 0 was found in 53.3%.Conclusions: Clinical and ultrasound scores decreased rapidly. Ultrasound scores were not associated with patient-reported variables. Half of the patients reached ultrasound remission, while there were large discrepancies in the percentage of patients reaching remission based on different CDAS.Trial registration: Study ML28691, registered 28 January 2014, ClinicalTrials.gov identifier: NCT02046616.

Low frequency of septic arthritis after arthrocentesis and intra-articular glucocorticoid injection.

Objective: The aim of this study was to evaluate the risk of septic arthritis (SA) in patients who received an intra-articular (IA) glucocorticoid (GC) injection and to describe the characteristics of these patients. Methods: All patients undergoing IA procedures at the orthopaedic and rheumatological departments on the Danish island of Funen from January 2006 to December 2013 were identified in the central database and included by register extraction. Patients who developed a clinically inflamed joint and positive synovial fluid culture within 14 days after IA GC injection were considered as having SA. Retrospectively, data on age, gender, affected joint location, bacterial agent, pre-existing inflammatory disorder, and death within 30 days were extracted from the patient files. According to local recommendations, a non-touch sterile technique was used for IA procedures. Patients were informed about the risk of SA and advised to seek medical attention on suspicion of infection or lack of improvement. Results: In total, 22 370 IA procedures were performed. Among these, 14 118 GC injections and 8252 arthrocenteses were undertaken. Only 11 patients were diagnosed with SA (0.08%, 95% confidence interval 0.03-0.12). Risk factors for SA were male gender, age, and pre-existing joint disease. Conclusion: We found a low frequency of SA subsequent to IA GC injections. Older patients with pre-existing joint disease are at higher risk of developing SA.

Prognostic factors associated with mortality in patients with septic arthritis: a descriptive cohort study.

OBJECTIVES: To evaluate the 30-day mortality rate of septic arthritis (SA) in adults in Funen, central Denmark, and to explore whether, at the time of SA presentation, risk factors for the 30-day mortality rate could be revealed. Our secondary objective was to describe the microbiological aetiologies, systemic signs of inflammation, and co-morbidity. METHOD: A descriptive study identifying patients with SA from central Denmark, during the period 2006-2013, by the use of joint fluid culture data retrieved from the electronic database at the Department of Clinical Microbiology, Odense University Hospital. Patients with a positive joint fluid culture were considered eligible and their medical records were examined. RESULTS: We identified 215 patients with SA, mean age 64.8 years. At presentation, mean C-reactive protein (CRP) was 204 mg/L, mean white blood cell count (WBC) 11.9 × 109/L, and mean body temperature 37.6°C. A total of 101 patients (47%) had a prosthetic joint, 46 (21%) had an inflammatory joint disease, and 24 (11%) had diabetes mellitus (DM). Staphylococcus aureus was the most common pathogen (104 patients, 48.4%). The 30-day mortality rate was 9.3% and the significant risk factor for death was liver disease at time of presentation [odds ratio (OR) 40.40, 95% confidence interval (CI) 5.38-303]. The other factors tested such as age > 65 years, elevated temperature, rheumatoid arthritis (RA), prostheses, and diabetes mellitus (DM) did not reach statistical significance. CONCLUSIONS: In our sample of patients with SA, we found a 30-day mortality rate in almost one in 10 adults. Among possible explanations, our study indicates that liver disease is a clinically relevant risk factor.

Doubling the single-dose infusion rate of tocilizumab in rheumatoid arthritis is safe and efficacious.

OBJECTIVES: To investigate the impact of enhanced infusion rate of tocilizumab on the occurrence of infusion reactions, overall safety, and efficacy in rheumatoid arthritis (RA). METHOD: We conducted a 24-week multicentre, open-label, randomized parallel group study comparing adverse event (AE) and effect profiles following tocilizumab IV 8 mg/kg every 4 weeks over 31 min vs. standard 60-min infusions in patients with RA and an inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARDs) and/or tumour necrosis factor (TNF)-α inhibitors. RESULTS: A total of 47 patients were enrolled in the study and randomized to fast infusions (n = 25) and controls (n = 22). Incidences of infusion reactions were similar between the two groups, neither of them leading to withdrawal. Likewise, the incidence of additional AEs did not differ between the treatment arms. Two serious adverse events (SAEs) were reported, in the control group. Four patients withdrew due to AEs, two from each arm. Efficacy at week 24 was comparable between groups. CONCLUSIONS: In RA, monthly tocilizumab infusions of 8 mg/kg provided over 31 or 60 min during 24 weeks did not differ concerning safety or efficacy.