IntroductionThe aim of this study was to assess a novel approach for the quantification of finger joint space narrowing and joint destruction in patients with rheumatoid arthritis (RA) focusing on the peripheral hand articulations.MethodsA total of 280 patients with verified RA underwent computerized semi-automated measurements of joint space distance at the finger articulations based on radiographs. The Z-Score, which can differentiate between joint space alterations caused by RA versus age/gender-related changes, was calculated as a comparative parameter. The severity of joint space narrowing was also quantified by the Sharp Score. Sensitivity and specificity of the Z-Score (based on joint space widths differentiated for each peripheral finger joint) were evaluated to reveal the potential for the occurrence of erosions. Additionally, the potential of the Z-Score regarding the differentiation of therapeutic effects on joint space widths in patients under a therapy of methotrexate versus leflunomide was performed.ResultsThe Z-Scores of finger articulations in patients with RA were generally decreased. Metacarpal-phalangeal (MCP) joint articulations showed a continuous significant decline of -1.65 ± 0.30 standard deviations dependent on the Sharp Score. The proximal-interphalangeal joints also revealed a significant reduction of the Z-Score (-0.96 ± 0.31 standard deviations). The sensitivity and specificity of MCP joint space distance for the detection of erosions were 85.4% versus 55.2%. The Sharp Score for joint space narrowing was not able to detect different treatments, whereas an accentuated stabilization of joint space narrowing could be identified for the Z-Score of the MCP joints in patients treated with leflunomide and methotrexate.ConclusionThe Z-Scoring method based on computer-aided analysis of joint space widths was able to reliably quantify severity-dependent joint space narrowing in RA patients. In the future, calculation of a Z-Score based on gender-specific and age-specific reference data shows the potential for a surrogate marker of RA progression that comprehends the early identification of patients with RA, and in particular those with erosive course of the disease, enabling a timely therapeutic strategy for cartilage protection.

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (≤1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of ≤5.1) was 71.9% at week 12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28 ≤ 2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies.

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Background The reduction of finger joint space width in patients with rheumatoid arthritis (RA) is associated with joint damage and physical function loss of the finger joints which results in physical disability. Objectives The Z-Score is a new computer based technique to measure joint space reduction on hand radiographs in RA in a gender- and age-independent way. The aim of this study was to quantify longitudinal changes of joint space width by the Z-Score in comparison to the Sharp joint space narrowing score. Methods 94 RA-patients (68 women and 26 men) participating at the LEMERADIX REGISTER (Retrospective Comparison of Leflunomide and Methotrexate in Rheumatoid Arthritis by Digital Radiogrammetry (DXR) and Computer-aided Joint Space Analysis (CAJSA)) as a prospectively planned, comparative, multicenter retrospective study were included. 53 patients were treated with 15 mg methotrexate per week and 41 patients were treated with 10 mg leflunomide per day over an observation period of 1.8 years. Hand radiographs were acquired at baseline and after 1.8 years. The quantification of finger joint space width of the metacarpal-phalangeal articulations (MCP) was performed by the Z-score using the computer-assisted joint space analysis (Version 1.3.6; Sectra; Sweden) and the Sharp joint space narrowing score. Results For both treatment arms (leflunomide and methotrexate) no significant changes of the Sharp Erosion Score and Sharp joint space narrowing score were observed over the observation period of 1.8 years. The median Sharp joint space narrowing score of the first and second measurement was 1. For the methotrexate treated patients the Z-Score (MCP total) decreased (-0.13 SD) from 0.08 SD (initial measurement) to -0.05 SD (second measurement). Regarding, the leflunomide-group the Z-Score (MCP total) was not significantly reduced (-0.03 SD) from 0.16 SD (initial measurement) to 0.13 SD (second measurement). Conclusions In this longitudinal head to head comparison based on the LEMERADIX-Register the conventional scoring of the finger joint space width by the Sharp joint space narrowing score revealed no change of the median joint space width. The automatically quantification of the joint space width using the Z-Score was able to detect changes of finger joint space width in patient groups with different treatment arms. Consequently, the automatic quantification of finger joint space width by the Z-Score is a sensitive technique for the quantification of joint space reduction and treatment effects. Disclosure of Interest A. Pfeil Speakers bureau: speaker’s fees from sanofi-aventis, J. Böttcher Speakers bureau: speaker’s fees from sanofi-aventis, K. Bornholdt Employee of: full-time employee of Sanofi-Aventis Deutschland GmbH, Germany, P. Oelzner: None Declared, G. Wolf: None Declared

in a linear manner with increasing dose [AUC t (mg-h/mL; mean 6 SD) for 0.15 mg/kg: 1260 6 254, 0.5 mg/kg: 4264 6 462, 1.0 mg/kg: 7818 6 652, 2.0 mg/kg: 15313 6 8478]. Mean t 1/2 ranged from 15.0 to 28.1 days. Bapineuzumab clearance was similar across dose groups (range: 0.12 -0.17 mL/h/kg). Plasma Aß x-40 levels increased with increasing doses of bapineuzumab (Fig. 2). No anti-bapineuzumab antibodies were found in any of the samples tested. Conclusions: Bapineuzumab was generally safe and well tolerated at doses of 0.15 mg/kg, 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg in Japanese patients with mild to moderate AD. The pharmacokinetic profile of bapineuzumab in Japanese patients is consistent with that observed in other studies with non-Japanese patients.