Haibel, H. et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 58, 1981-1991

Charité Medical University Hospital, Campus Benjamin Franklin, Berlin, Germany.
Arthritis & Rheumatology (Impact Factor: 7.76). 07/2008; 58(7):1981-91. DOI: 10.1002/art.23606
Source: PubMed


To evaluate the efficacy and safety of the tumor necrosis factor (TNF) antagonist adalimumab in patients with axial spondylarthritis (SpA) without radiographically defined sacroiliitis refractory to conventional treatment.
Patients with active axial SpA (n = 46) were randomized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension that continued up to week 52. The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria, including 2 of the following 3 criteria: inflammatory back pain, HLA-B27 positivity, or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging, in the absence of radiographic evidence of sacroiliitis. The primary end point was a 40% response according to the improvement criteria of the Assessment of SpondyloArthritis international Society (ASAS40).
All 46 patients (22 receiving adalimumab and 24 receiving placebo) completed the 12-week trial; 38 patients completed the extension period to week 52. At week 12, an ASAS40 response was achieved by 54.5% of the adalimumab-treated patients, as compared with 12.5% of the placebo-treated patients (P = 0.004). After switching to adalimumab, a similar degree of efficacy was also achieved by the patients who were initially treated with placebo. Efficacy was maintained in all patients until week 52. Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response. Serious adverse events occurred in 5 patients, none of which was related to the study drug.
Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis.

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Available from: Joachim Listing, Oct 10, 2014
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    • "Clinical trials have shown efficacy of anti-TNFα agents in inflammatory back pain classified as nonradiologic axial SpA in patients who had magnetic resonance imaging (MRI) findings of sacroiliitis, with partial remission rates of greater than 50%. This response rate was better than that seen in patients with established ankylosing spondylitis.33 "
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    ABSTRACT: The axial spondyloarthropathies are a group of chronic inflammatory diseases that predominantly affect the axial joints. This group includes ankylosing spondylitis and nonradiographic axial spondyloarthropathy. While the pathogenesis of axial spondyloarthropathies is not clear, immunologically active tissues primarily include the entheses, ie, the areas where ligaments, tendons, and joint capsules attach to bone and to the annulus fibrosis at the vertebrae. One of the major mediators of the immune response in this group of diseases is tumor necrosis factor-alpha (TNFα). Blockade of TNFα results in reduced vascularity and inflammatory cell infiltration in the synovial tissues of affected joints. Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNFα monoclonal antibody. CZP has unique properties that differ from other available TNFα inhibitors by virtue of its lack of an Fc region, which minimizes potential Fc-mediated effects, and its PEGylation, which improves drug pharmacokinetics and bioavailability. It has been shown in clinical trials that CZP improves patient outcomes and reduces inflammation in the sacroiliac joints and spine in both ankylosing spondylitis and nonradiographic axial spondyloarthropathies. These data support CZP as a treatment option for axial spondyloarthropathies.
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    • "Similar or even higher response rates were recently found in patients with nr-axSpA [5,6]. Younger age, shorter symptom duration or elevated C-reactive protein (CRP) values were found to be predictive of a Bath ankylosing spondylitis disease activity index (BASDAI)-50 response or an assessment of the SpondyloArthritis International Society (ASAS)-40 [5,7-9] response to TNF-blockers [5,10]. "
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    ABSTRACT: The aim of this study was to investigate the influence of symptom duration on treatment response and on the correlation between improvements in patient reported outcomes (PRO) and objective inflammation in patients with axial spondylarthritis (SpA) treated with etanercept (ETA) or adalimumab (ADA). Data from 112 patients with axial SpA originally enrolled in two randomized controlled clinical trials were pooled and analyzed after one year of treatment with ETA (n = 66) or ADA (n = 46). Patients with <4 years and ≥4 years of disease were compared for improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP) and magnetic resonance imaging (MRI) score for sacroiliac joints (SIJ). Patients with <4 years of disease showed a significantly better improvement than longer diseased patients in BASDAI (3.2 (95% confidence interval (CI): 2.7 to 3.7) vs. 1.7 (1.1 to 2.2)), BASFI, BASMI and ASDAS (1.6 (1.4 to 1.8) vs. 0.9 (0.7 to 1.1)). The change in BASDAI showed a significant correlation with the change in SIJ score (Spearman’s rank correlation coefficient (rho) = 0.37, P = 0.01) and the change in CRP (rho = 0.45, P = 0.001) in patients with <4 years of disease. For long diseased patients this correlation was poor and did not achieve statistical significance (rho = 0.13, P = 0.46; rho = 0.22, P = 0.13 respectively). The low correlation between change of PROs and change of objective signs of inflammation seen in axial SpA patients with longer symptom duration treated with tumor necrosis factor-blocker seems to indicate that inflammation is not the only cause of the patients’ symptoms, while inflammation seems to be the major cause in short diseased patients. Trial registration Clinical NCT00844142 (Trial 1); NCT00235105 (Trial 2)
    Full-text · Article · Jan 2014 · Arthritis research & therapy
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    • "Anti-TNF agents are effective in adults with early axial inflammation that is detectable by MRI but not by radiographs.56 Once sacroiliitis has developed and damage is detectable on radiographs, DMARDs and anti-TNF agents may help symptomatically, but they do not inhibit progression of axial structural damage.57–60 "
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    ABSTRACT: Juvenile idiopathic arthritis (JIA) is a chronic, inflammatory disease of unknown etiology. The enthesitis-related arthritis (ERA) JIA category describes a clinically heterogeneous group of children including some who have predominately enthesitis, enthesitis and arthritis, juvenile ankylosing spondylitis, or inflammatory bowel disease-associated arthropathy. ERA accounts for 10%-20% of JIA. Common clinical manifestations of ERA include arthritis, enthesitis, and acute anterior uveitis. Axial disease is also common in children with established ERA. Treatment regimens for ERA, many of them based on adults with rheumatoid arthritis and ankylosing spondylitis, include the use of nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologic agents either individually or in combination.
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