Alternative for anti-TNF antibodies for arthritis treatment.

Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α remain refractory or become nonresponder to these treatments. In this context, there is a need for new or complementary therapeutic strategies. In this study, we investigated in vitro and in vivo anti-inflammatory potentialities of an anti-TNF-α triplex-forming oligonucleotide (TFO), as judged from effects on two rat arthritis models. The inhibitory activity of this TFO on articular cells (synoviocytes and chondrocytes) was verified and compared to that of small interfering RNA (siRNA) in vitro. The use of the anti-TNF-α TFO as a preventive and local treatment in both acute and chronic arthritis models significantly reduced disease development. Furthermore, the TFO efficiently blocked synovitis and cartilage and bone destruction in the joints. The results presented here provide the first evidence that gene targeting by anti-TNF-α TFO modulates arthritis in vivo, thus providing proof-of-concept that it could be used as therapeutic tool for TNF-α-dependent inflammatory disorders.

Does joint effusion influence the clinical response to a single Hylan GF-20 injection for hip osteoarthritis?

OBJECTIVE: To evaluate the influence of a joint effusion on the clinical response to a single injection of Hylan GF-20 for hip osteoarthritis. METHOD: We prospectively included patients scheduled for intraarticular Hylan GF-20 injection to treat hip osteoarthritis. Disease severity was assessed based on the Kellgren-Lawrence radiological grade. Ultrasonography was performed to look for a joint effusion. The pain score on a visual analog scale, Lequesne algofunctional index, and WOMAC scores were recorded at baseline and 1, 3, and 6 months postinjection. The proportions of patients who met OARSI response criteria and who achieved Patient Acceptable Symptom State (PASS) thresholds were determined in the overall population and in the groups with and without a joint effusion at baseline. RESULTS: Of 55 included patients, 24 (44%) had an effusion at baseline. The baseline Lequesne index was significantly higher in the group with an effusion (11.9+/-3.6 versus 8.4+/-4.5) (p=0.003). The proportions of OARSI responders in the overall population were 31.8%, 39.4%, and 14.8% after 1, 3, and 6 months, respectively. The proportions of patients who achieved the PASS for pain and function were 52.4% and 50.0% after 1 month, 67.7% and 54.5% after 3 months, and 60.0% and 50.0% after 6 months, respectively. Presence of an effusion at baseline had no effect on any of the clinical response parameters. CONCLUSION: Presence of a joint effusion is associated with worse pain and functional impairment at baseline but has no influence on the clinical response to Hylan GF-20 in patients with hip osteoarthritis.

A particular form of septic arthritis: septic arthritis of facet joint.

Only about 40 cases of septic arthritis of the facet joints have been reported to date. We report 6 new cases including 2 at the cervical spine, which is rarely involved. Mean age was 61.5 years; there were 5 men and 1 woman. Spinal pain and stiffness, fever, and asthenia were the presenting manifestations. Laboratory tests consistently showed inflammation. Among classical risk factors for infection, only noninsulin-dependent diabetes was noted, in a single patient. Mean time to the diagnosis was 42 days. Discitis, a far more common condition, was considered initially, and early radiographs were of limited diagnostic assistance. Radionuclide bone scans identified the site of the infection and served to look for other foci. Magnetic resonance imaging was effective in confirming the diagnosis at an early stage and in looking for local spread (muscles, epidural space, and disk). L3-L4 was involved in 3 patients, C4-C5 in 2, and L4-L5 in 1. Direct inoculation during mesotherapy sessions was the cause in 1 patient. Cultures of blood and needle biopsy samples were positive in all 6 cases; Staphylococcus aureus was the causative agent in 3 patients. The risk of local and systemic complications governs the prognosis of facet joint infection. Of our 6 patients, 4 experienced complications: there was 1 case each of discitis, epidural infection, endocarditis, and septic arthritis of the acromioclavicular joint. Fatal multiple organ dysfunction occurred in 1 patient. In the other 5 patients, antimicrobial therapy and protection from weight-bearing for 3 months ensured a favorable outcome.

Inflammatory and structural evaluation in spondyloarthritis: magnetic resonance imaging analysis of axial and peripheral involvement.

OBJECTIVE: To determine the magnetic resonance imaging (MRI) criteria of most value in the assessment of patients with spondyloarthropathy (SpA) with axial or peripheral involvement. METHODS: Fat suppressed (FS)-T2 and pre- and postinjection FS-T1 images were obtained in the most symptomatic region (axial or peripheral) of patients requiring tumor necrosis factor-a blockers. Thirty-eight MRI (21 axial and 17 peripheral) were blindly scored at synovial (S) and entheseal (E) sites by 2 experienced observers screening for 7 inflammatory and 7 structural predefined criteria, which were evaluated for frequency (N) and intra- and interobserver reproducibility. RESULTS: In peripheral regions, synovitis (S; N = 69.4%), ligament inflammation (E; N = 39.7%), bone marrow edema (S; N = 22.1%; E; N = 15%), and tenosynovitis (S; N = 21%) were recorded with good to excellent intraobserver reproducibility [intraclass correlation coefficient (ICC) 0.49-0.93] and moderate to good interobserver reproducibility (ICC 0.49-0.66). With regard to structural criteria, erosions (S; N = 17.1%) and enthesophytes (E; N = 13.9%) exhibited good to excellent intraobserver (ICC 0.71-0.85) and moderate interobserver reproducibility (ICC 0.54-0.49); the reproducibility of fat inflation (N = 1.4%) was good (ICC 0.76-0.78). In axial regions, no inflammatory criteria achieved good interobserver reproducibility. However, fat inflation (S; N = 86%), chondral lesions (S; N = 85.8%), enthesophytes (E; N = 76.7%), fusion (S; N = 41.2%), and erosions (S; N = 25.1%) showed excellent intraobserver reproducibility (ICC 0.81-0.98), and moderate to excellent interobserver reproducibility (ICC 0.50-0.96). CONCLUSION: In terms of intra- and interobserver reproducibility, MRI is a reliable tool with which to assess synovitis, bone edema, ligament inflammation, tenosynovitis, erosion, enthesophytes, and fat inflation in patients with peripheral involvement. In those with axial involvement, inflammatory criteria lack interobserver reproducibility, but chondral lesions, erosion, fat inflation, fusion, and enthesophytes are relevant.

Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity.

OBJECTIVE: To determine the magnetic resonance imaging (MRI), macroscopic, and microscopic characteristics of synovial membrane inflammation, to study the relationship between disease severity and the degree of synovial inflammation on MRI and on macroscopic and microscopic examination, and to look for colocalization of chondral lesions and synovial inflammation. METHODS: Thirty-nine patients with knee osteoarthritis (OA) were classified into 2 groups according to the severity of cartilage lesions as revealed by chondroscopy. Group 1 (n = 14) had mild cartilage lesion(s) without exposure of subchondral bone. Group 2 (n = 25) had severe cartilage lesion(s) with focal or diffuse exposure of subchondral bone. Synovitis was evaluated on T1-weighted MRI sequences according to the degree of synovial thickening on a 4-point scale (ranging from 0 to 3) in 5 regions of interest. Synovial membrane was macroscopically scored, and biopsies were performed on the 5 preselected sites for histologic scoring. RESULTS: The mean +/- SD synovial thickening score on MRI was 1.55 +/- 0.90, with no significant difference between groups 1 and 2. Intra- and interobserver reproducibility of the total synovial score was excellent, and interobserver reproducibility of the MRI grade was good. Synovitis was diffuse and associated with chondral lesions only in the medial femorotibial compartment (r = 0.49, P = 0.001). The degree of synovial thickening on MRI correlated with qualitative macroscopic analysis (r(s) = 0.58, P < 0.001) and with microscopic features (synovial lining cells [r(s) = 0.23, P < 0.007], surface fibrin deposition [r(s) = 0.12, P < 0.01], fibrosis [r(s) = 0.31, P < 0.006], edema [r(s) = 0.17, P = 0.07], congestion [r(s) = 0.30, P < 0.005], and infiltration [r(s) = 0.46, P < 0.0001]). Fibrin and infiltration parameters were more severe in end-stage disease (P = 0.009 and P = 0.02, respectively). CONCLUSION: Synovitis may be present from the onset of OA and may be evaluated on MRI. MRI evaluation of synovitis could be used to classify OA patients in clinical trials and could help to identify those who could benefit from synovium-targeted therapy.