AB1172 Does ultrasound-scored synovitis depend on the pharmacokinetics of intravenous infliximab in patients with rheumatoid arthritis?. (12th June 2018) - Ishchenko, A.
Abstract : Background: Musculoskeletal ultrasound (US) was developed more than four decades ago and gradually made its way to daily rheumatological practice. This dynamic, non-irradiating and relatively inexpensive technique allows detection of synovitis/tenosynovitis as well as quantification of joint inflammation. However, several external factors, such as, joint position, machine settings, sonographer expertise and certain medications can influence the results of the US examination. Objectives: The aim of this study was to investigate whether the pharmacokinetics of intravenous ( i.v. ) infliximab (IFX) influences the grade of US detected synovitis, measured by gray-scale (GS) and colour Doppler (CD) in rheumatoid arthritis (RA) patients. Methods: Inclusion criteria were RA patients with at least one swollen joint, being treated with i.v. IFX, who had neither, changes in DMARD therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory and US assessment at three time points: at trough, peak plasma drug concentration and at mid-cycle. US assessments were performed blindly to the clinical and laboratory data. Twenty-four joints were assessed for the presence and grade (0–3) of GS synovitis and synovial CD signal: elbows, wrists, 2nd-5th metacarpophalangeal (MCP) joints, knees, ankles, 2nd-5th metatarsophalangeal (MTP) joints. A global OMERACT-EULAR synovitis score (GLOESS) as well as the sum of GS and CD scores were calculated for the 24-joint set, for the 12-joint set (Naredo score) and for wrists-MCP-ankles-MTP joints. Several disease activity scores (DAS) [28-joint DAS (DAS28-CRP), Simplified Disease Activity Index (SDAI)] and health assessment questionnaire (HAQ) were assessed in all patients. Trough plasma IFX concentrations were available in 20 patients. Results: Twenty-two RA patients were prospectively recruited from the biologic therapy unit of our hospital. Two thirds of patients were female and mean age was 61 years. The majority of them had long-standing seropositive RA and over 90% had radiographic damage. The median of IFX treatment duration was 9 years. There were no significant differences between the GS, CD and GLOESS scores at IFX peak time and trough time. US-joint count, GS, CD and GLOESS scores did not significantly differ between peak time and trough time. Patients with long-lasting RA treated with IFX had relatively stable US-detected synovitis and slightly lower clinical scores at 4 weeks after IFX administration as compared to baseline. The DAS28CRP, 28 and 44 swollen joint counts did not correlate with trough serum IFX concentrations. US scores (GS and GLOESS) significantly correlate with trough serum IFX concentrations (Spearman correlation coefficient, r=−0.55, p=0.01, n=20). Patients with low trough IFX levels, especially ≤1 µg/ml, had higher US joint count as well as US scores (p<0.01). Reference: [1] US-scored synovitis is not significantly influenced by pharmacokinetics of IFX in RA patients. US examination can be conducted independently of time of IFX administration i.e. before or after IFX administration in clinical trials. Although there was no correlation with clinical scores, low trough IFX concentration correlated with the degree of US-detected synovitis. Disclosure of Interest: None declared