Efficacy of anti-TNF in patients with spondyloarthritis in absence of any imaging sign.

OBJECTIVE: Some clinical pictures satisfy spondyloarthritis criteria without any detected imaging signs and the question sometimes arises in clinical daily practice if biologics should be started. Our aim was to evaluate anti-TNF efficacy in patients with clinical but not imaging (radiographic, CT-scan, MRI) signs of spondyloarthritis. METHODS: This retrospective study concerned patients with axial spondyloarthritis fulfilling European Spondyloarthritis Study Group (ESSG) criteria, treated with anti-TNF after failure of conventional therapies. Therapeutic responses, rated according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)-50% or 20 mm and ASAS-20 or -40 definitions, were evaluated after 12 months. Factors associated with those responses were also sought. Propensity score was used to check thereafter whether there were interactions with some baseline variables. RESULTS: Among 385 patients included, 257 with imaging signs had significantly more frequent therapeutic responses (P=0.0005). About 40% of the spondyloarthritis patients without imaging signs responded to anti-TNF. The response rate was significantly higher in HLA-B27 carriers with initial imaging signs (P=0.028). Furthermore, responders were younger at biotherapy onset, with lower Bath Ankylosing Spondylitis Functional Index (BASFI) and pain visual analog scale score, and higher C-reactive protein (CRP), compared to non-responders. After weighted calculation, the prediction of response to TNF-blockers was quite similar in both groups. CONCLUSION: The percentage of patients with exclusively clinical signs who responded to anti-TNF was far from negligible. Regardless the HLA-B27 status, having imaging signs of spondyloarthritis does not provide a superiority of response to anti-TNF compared to the absence of imaging sign. The absence of any imaging sign in patients with spondyloarthritis should therefore not lead to the exclusion of anti-TNF therapy.

Synovium CD20 expression is a potential new predictor of bone erosion progression in very-early arthritis treated by sequential DMARDs monotherapy -- a pilot study from the VErA cohort.

OBJECTIVE: Because available biomarkers (rheumatoid factors [RF], anti-cyclic citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to predict rheumatoid arthritis (RA) structural damage, to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s). METHOD: The study was conducted on 18 prospectively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve, VErA cohort patients with very-early arthritis (median duration: 4months). Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes, anti-CCP2, osteoprotegerin, receptor activator of nuclear κB-ligand [RANK-L] and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global inflammation index) for a metacarpophalangeal joint-synovium biopsy. Baseline and 3-year hand-and-foot X-rays were graded with the van der Heijde-modified-Sharp score; the judgment criterion was its progression during follow-up. Pearson's product moment correlation statistics were used to test for association between paired samples. RESULTS: A baseline, a significant relationship was found between erosive damage and markers of B-cell activation, notably the synovium CD20 expression (r=0.68; P=0.0001). Quantified by the modified-Sharp erosion score variation, the 3-year structural damage progression was significantly correlated with: serum levels of RF-IgG (r=0.75; P=0.0003), -IgM (r=0.69; P=0.001), anti-CCP2 (r=0.53; P=0.02) and RANK-L (r=0.61; P=0.007); synovium CD20 expression (r=0.70; P=0.001). CONCLUSION: This analysis of the prognostic value of a large panel of synovium markers in a limited sample of prospectively followed, well-documented patients suggested that both synovial CD20 and serum RANK-L levels might be new predictors of structural damage progression in very-early RA.

A 3 mg/kg starting dose of infliximab in active spondyloarthritis resistant to conventional treatments is efficient, safe and lowers costs.

OBJECTIVE: We assessed the efficacy, tolerance and cost of a 3 mg/kg starting dose of infliximab for ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: We retrospectively followed-up 45 biologic-naive consecutive patients (11 with axial AS, 24 with axial and peripheral [mixed] AS and 10 with PsA) who were treated between 2002 and 2005 with a 3 mg/kg dose of infliximab after failure of conventional therapies. The following variables were recorded: visual analog scale (VAS) scores of patient's global (G) and pain (P) assessment, duration of early morning stiffness (EMS), disease activity (BASDAI) and functional disability (BASFI). Treatment responses were assessed at 6 and 12 months using the AS assessment score (ASAS)-20% and -40% criteria and BASDAI-50. RESULTS: Baseline characteristics of the 29 men and 16 women were (median [range]): G-VAS, 70 [13-100]; P-VAS, 70 [13-100]; EMS, 60 [0-180] minutes; BASDAI, 64.4 [23.9-100]; BASFI, 57.2 [3.5-98.5]. All manifestations regressed significantly (p<0.0001) for 39 (86.7%) and 24 (53.5%) patients at 6 and 12 months, respectively; 26 (57.8%) had achieved ASAS-20 responses at 6 months that persisted at 1 year for 20 (44.4%); 19 (42.2%) and 12 (26.7%) satisfied BASDAI 50 criteria at 6 and 12 months, respectively. Interestingly, almost 30% still received low-dose infliximab after 4 years of follow-up. CONCLUSION: An initial dose of 3 mg/kg of infliximab significantly attenuated AS and PsA manifestations in>40% of the patients, making use of this dose highly advantageous in terms of safety and 33% lower cost.

[Anti-TNF alpha in the treatment of rheumatoid arthritis and ankylosing spondylitis]. / Anti-TNF alpha dans le traitement de la polyarthrite rhumatoïde et de la spondylarthrite ankylosante.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are, with psoriatic arthritis, the most frequent rheumatic diseases. A better understanding of pathophysiology of these diseases had led to the development of new treatments refered as to biologic agents and, among them, TNF blocking agents have a major role. The knowledge of these drugs in terms of mechanisms of action, indications and potentials side effects has to be known to improve the efficacy/tolerance balance. Although these 3 anti-TNFalpha agents are currently used, new TNF blocking agents are under evaluation and should increase the number of drugs available within the next months.