Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter, randomized, double‐blind, placebo‐controlled study

Lambert, Robert G.; Salonen, David; Rahman, Proton; Inman, Robert D.; Wong, Robert; Einstein, Steven; Thomson, G. T. D.; Beaulieu, André; Choquette, D.; Maksymowych, Walter P.

doi:10.1002/art.23044

Cited by 238 publications

(147 citation statements)

References 22 publications

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“…Dougados et al (14) performed a double-blind randomized controlled trial in 215 patients with nonradiographic axial SpA, in which a decrease in SPARCC score of the SI joints of 46.9% (3.8 units) in patients treated with etanercept was observed versus a decrease of 10.9% (0.8 units) in placebo-treated patients at week 12. In a randomized controlled trial of adalimumab in 82 predominantly male AS patients, a significant decrease of 52.9% (9.3 units) in SPARCC scores of the SI joints was observed in adalimumab-treated patients after 12 weeks of therapy, whereas a decrease of only 12.7% (1.3 units) was observed in placebo-treated patients (15). In the Ability-1 Trial of adalimumab in nonradiographic axial SpA, a mean decrease of 62.7% (3.2 units) in SPARCC score for the SI joint was reported, while the placebo responses showed a decrease of 12.8% (0.6 units) (16).…”

Section: Discussionmentioning

confidence: 97%

Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints

Varkas

Jans

Cypers

et al. 2016

Arthritis & Rheumatology

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Objective. To evaluate the early effect of full-dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA).Methods. A single-center, 6-week study of a cohort of consecutive patients with clinically suspected axial SpA was conducted. A total of 117 patients were screened. Forty patients who were diagnosed as having axial SpA and had presented with a positive MRI of the SI joints as defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria were considered for a followup MRI after 6 weeks of an optimal dose of NSAIDs. Twenty patients completed the study. Disease activity was monitored by determining the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score every 2 weeks and the Bath Ankylosing Spondylitis Functional Index score at baseline and week 6. NSAID intake was assessed by the ASAS NSAID index. Primary end points were improvement in bone marrow edema of the SI joints on MRI and BASDAI response at week 6.Results. Approximately one-third of eligible patients newly diagnosed as having axial SpA were unable to continue the full-dose NSAID schedule. The median NSAID index was 97% in patients who completed the study. There was a reduction of 1.1 units (10.5%) in mean SpondyloarthritisResearch Consortium of Canada (SPARCC) scores at week 6 in comparison to baseline (P 5 0.032). Overall, only 30% of the patients (6 of 20) had a minimal clinically important difference of ‡2.5 in SPARCC score. However, 80% of the patients displayed high-intensity lesions on STIR images at baseline, which decreased significantly at week 6 (P 5 0.011). There was a significant decrease in the relative intensity of the region of interest (P 5 0.007) and a mean decrease of 0.6 in the BASDAI score per 2 weeks of therapy (P 5 0.001). Only 29.4% of the patients met the BASDAI criteria for 50% improvement (BASDAI50) at week 6.Conclusion. Our findings indicate a high level of dropout among patients receiving full-dose NSAID therapy in daily practice. In those who tolerated NSAID therapy, there was no clinically relevant decrease in SPARCC scores and low BASDAI50 response. However, we found a decrease in signal intensity of bone marrow edema of the SI joints as an early response to 6 weeks of optimal NSAID therapy in patients newly presenting with axial SpA.

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Section: Discussionmentioning

confidence: 97%

Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints

Varkas

Jans

Cypers

et al. 2016

Arthritis & Rheumatology

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“…In a randomized controlled trial of patients with longstanding AS, evaluation of changes in the SPARCC MRI scores of the spine and SI joints demonstrated a significant reduction in inflammation following treatment with the TNF-α inhibitor adalimumab versus placebo at Week 12 12 . These results indicate that changes in BME can be detected using the SPARCC MRI indices as early as 12 weeks after initiation of effective therapy.…”

Section: Rheumatologymentioning

confidence: 99%

Defining the Minimally Important Change for the SpondyloArthritis Research Consortium of Canada Spine and Sacroiliac Joint Magnetic Resonance Imaging Indices for Ankylosing Spondylitis

Maksymowych¹,

Lambert²,

Brown³

et al. 2012

J Rheumatol

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Objective.To define the minimally important change (MIC) in the SpondyloArthritis Research Consortium of Canada (SPARCC) spine and sacroiliac (SI) joint magnetic resonance imaging (MRI) indices in patients with ankylosing spondylitis.Methods.MRI scans were performed during a placebo-controlled trial of adalimumab (no. NCT00195819). Two independent readers, blinded to treatment and sequence, determined SPARCC scores for the spine and SI joints and a global evaluation of change (GEC; “much worse,” “worse,” “no change,” “better,” or “much better”; categories other than “no change” were pooled together as “change”) between baseline–Week 12, baseline–Week 52, and Weeks 12–52. Mean absolute changes in SPARCC scores (95% CI) were calculated for each interval, treatment group, and GEC. Receiver-operating characteristic (ROC) curves were used to identify the MIC. Relationships of MIC to clinical responses were examined.Results.Reader agreement on GEC evaluations was > 70%. Changes in SPARCC scores were generally comparable between time intervals and treatment groups for “change” and “no change” categories and were combined for each category; change in score was significantly associated with GEC of “change” (area under ROC curves: spine 0.839; SI joints 0.960). ROC curves peaked at values of 5.0 for the spine and 2.5 for SI joints. Placebo-treated patients achieving > 2.5 unit improvement in SI joint score had significantly better clinical responses than placebo-treated patients who did not achieve such improvement. MRI and clinical responses were uncoupled in adalimumab-treated patients.Conclusion.We propose that changes of 5.0 for the spine and 2.5 for SI joints define the MIC for the SPARCC MRI indices.

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“…The former are thought to evolve into Romanus lesions and the latter are thought to reflect spondylodiscitis. It has been shown that the severity of the MRI changes correlates with the histopathologic grading of inflammation (7), and reductions in active inflammatory lesions are readily visible on MRI within a few weeks following initiation of anti-TNF treatment (8)(9)(10).…”

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confidence: 99%

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Chiowchanwisawakit

Lambert

Conner‐Spady

et al. 2011

Arthritis & Rheumatism

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Objective. Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte.Methods. MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n ‫؍‬ 38) and an observational cohort (n ‫؍‬ 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n ‫؍‬ 36) or anti-TNF therapy (n ‫؍‬ 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings.Results. New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either Conclusion. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.A hallmark of ankylosing spondylitis (AS) is the development of new bone in the spine, which typically leads to ankylosis across the disc spaces. Bone proliferation typically starts at the vertebral rim and grows in the direction of the anulus fibrosus, parallel to the vertebral axis. Ossification may extend across the vertical length of the anulus and becomes visible on radiographs as a syndesmophyte.Until recently, it was hypothesized that ankylosis occurred in response to inflammation and following a reparative process that included cartilage metaplasia. However, data from animal models of spondylarthritis (SpA), principally ankylosing enthesitis, directly challenged this hypothesis by demonstrating that anti-tumor necrosis factor ␣ (anti-TNF␣) therapy did not prevent the development of ankylosis (1). An alternative hypothesis was then proposed whereby pathogenetic factors such as altered gene expression, biomechanical factors, and bacteria trigger the concomitant expression of inflammation and new bone formation, which then proceed

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Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter, randomized, double‐blind, placebo‐controlled study

Cited by 238 publications

References 22 publications

Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints

Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints

Defining the Minimally Important Change for the SpondyloArthritis Research Consortium of Canada Spine and Sacroiliac Joint Magnetic Resonance Imaging Indices for Ankylosing Spondylitis

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

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