Clinical and Imaging Efficacy of Infliximab in HLA-B27-Positive Patients With Magnetic Resonance Imaging-Determined Early Sacroiliitis

University of Leeds, Leeds, UK.
Arthritis & Rheumatology (Impact Factor: 7.76). 04/2009; 60(4):946-54. DOI: 10.1002/art.24408
Source: PubMed


To evaluate the efficacy of infliximab in HLA-B27-positive patients with magnetic resonance imaging (MRI)-determined early sacroiliitis, using both clinical and MRI assessments.
Forty patients with recent-onset inflammatory back pain, as assessed by the Calin criteria, HLA-B27 positivity, clinical disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain and morning stiffness, and magnetic resonance imaging (MRI)-determined sacroiliac joint bone edema were randomized in a double-blind manner to receive infliximab 5 mg/kg or placebo at 0, 2, 6, and 12 weeks. MRI scans were performed at baseline and 16 weeks and scored by 2 observers (blinded to both the order of the scans and to treatment group), using the Leeds scoring system. Clinical assessments included the BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL) instrument, the ASsessment in Ankylosing Spondylitis International Working Group criteria (ASAS) for improvement, and markers of inflammation.
The mean reduction in the total MRI score from week 0 to week 16 was significantly greater in infliximab-treated patients compared with placebo-treated patients (P = 0.033). On average, significantly more lesions resolved in the infliximab group (P < 0.001), while significantly more new lesions developed in the placebo group (P = 0.004). Significantly greater improvement in the infliximab group versus the placebo group was also observed for changes from week 0 to week 16 in the BASDAI (P = 0.002), BASFI (P = 0.004), and ASQoL (P = 0.007) scores. Responses according to the ASAS criteria for 40% improvement, the ASAS criteria for 20% improvement in 5 of 6 domains, and ASAS partial remission were achieved by 61%, 44%, and 56% of infliximab-treated patients, respectively. Infliximab was well tolerated, and no serious adverse events were observed.
Infliximab was an effective therapy for early sacroiliitis, providing a reduction in disease activity by week 16. This study is the first to show that infliximab is effective for reducing clinical and imaging evidence of disease activity in patients with MRI-determined early axial spondylarthritis.

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Available from: Paul Emery, Sep 23, 2014
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    • "The effects of etanercept therapy in this study are similar to findings in adult spondyloarthropathy where anti-TNF therapy improves inflammatory lesions but does not improve structural damage in the SI joint. [26] The reason for persistent or worsening erosions after therapy is unclear. Therapy may have no effect or a slower effect on structural damage. "
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    ABSTRACT: Background Magnetic resonance imaging (MRI) is often used to diagnose and monitor treatment effects of juvenile spondyloarthropathy (SpA). Our objective was to describe MRI findings in juvenile SpA and determine predictors of active sacroiliitis and response to treatment. Methods Children who had MRI of the sacroiliac (SI) joints and were referred to the pediatric rheumatology clinic from 2009 to 2012 were retrospectively studied. The clinical parameters, laboratory studies and findings on MRI were collected and a composite score ratio (CR) was calculated for both SI joints on each MRI study based on a semi-quantitative scale that included evaluation of bone marrow edema (BME), synovial enhancement (SE), and erosions (ER). The findings on MRI were correlated with clinical and laboratory values. Results 50 subjects who underwent 76 MRI for suspected or known SpA were included in the study. Sacroiliitis was seen in 48 MRIs in 32 subjects. Of the subjects with sacroiliitis, mean age ± standard deviation was 13.7 ± 2.6 years, 71% were male and 41% were HLA B27 positive. SE without BME was seen in 31% cases of sacroiliitis. In subjects with sacroiliitis, 79% also had hip arthritis and 41% had enthesitis of the pelvic region on MRI. In 38% of subjects with sacroiliitis, physical exam was not indicative of sacroiliitis or hip arthritis. Longitudinal data were available for 13 subjects. Sacroiliitis on MRI improved in 9 subjects with the greatest improvement in MRI composite score ratio after initiation of etanercept therapy. CR improvement was due to improvement of BME and SE components, while the ER score remained the same or worsened in all but 1 subject. Conclusion History, physical exam or laboratory data may not predict sacroiliitis in children. Magnetic resonance imaging plays a valuable role in the initial evaluation and later treatment monitoring of children with spondyloarthropathy. Synovial enhancement is significantly reduced after treatment, and unlike adults, synovial enhancement may be detected without accompanying bone marrow edema, which suggests gadolinium contrast may be an important component in the assessment of children with spondyloarthropathy.
    Full-text · Article · Jul 2014 · Pediatric Rheumatology
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    • "In the INFAST trial, 40 to 48% of patients who received early infliximab treatment remained in drug-free remission 6 months after stopping their infliximab [15]. In the Barkham and colleagues study mentioned above of infliximab in early axSpA, after only four infusions 33% (four of 12) of patients remained symptom free 5 years after treatment, whereas 100% (13 of 13) of patients initially randomized to placebo were still requiring TNFi therapy [6,16]. The definition of flare varies between studies, and standardization of this definition as well as other issues relating to trial design would enable better conclusions to be drawn. "
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    ABSTRACT: The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.
    Full-text · Article · May 2014 · Arthritis Research & Therapy
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    • "Although these subgroups were of small size these results suggest a cutoff of around 4 years can be used to identify a window of opportunity for early therapy regarding a good treatment response to TNF-blockers. Indeed, symptom duration of less than 3 years [6,16] or less than 5 years [13] have been associated with a clinical remission rate of about 50% in axSpA patients treated with TNF-blockers, and a cutoff of 5 years of symptoms differentiated good and bad responders in an nr-axSpA trial with ADA [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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