Recent advances in ankylosing spondylitis: understanding the disease and management

Garcia-Montoya, Leticia; Gul, Hanna; Emery, Paul

doi:10.12688/f1000research.14956.1

Cited by 99 publications

(89 citation statements)

References 102 publications

(98 reference statements)

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“…IL-17 can therefore both promote bone formation in areas of inflammation and also, in action with TNF, bone destruction. 56 These findings have resulted in the development of targeted therapies aimed at inhibiting these inflammatory cytokines. However, although the clinical efficacy of biologic treatment has been established in patients with axSpA, [16][17][18] their impact on spinal radiographic progression has proven more difficult to establish.…”

Section: Discussionmentioning

confidence: 99%

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

Baraliakos

Gensler

D’Angelo³

et al. 2020

Therapeutic Advances in Musculoskeletal

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We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion. Bias was assessed using the methodological index for nonrandomized studies (MINORS) tool. Among the 322 studies identified in the literature search, 23 (11 OLEs and 12 cohort studies) met the eligibility criteria and were selected for inclusion. Most studies reported mSASSS progression in patients with AS receiving tumor necrosis factor inhibitor (TNFi) treatment. One study reported mSASSS progression in patients with AS treated with secukinumab, an interleukin-17A inhibitor. The mean (range) MINORS score was 11.3 (7-15) for the 15 noncomparative studies and 15 (12-22) for the 8 comparative studies. Although results of the individual studies were variable, mSASSS progression in patients with AS was generally minimal and slow with long-term TNFi therapy. Moreover, odds ratios for the likelihood of mSASSS progression with/without TNFi favoured TNFi therapy in several of the cohort studies. The rate of mSASSS progression following continuous secukinumab treatment was low and remained stable over 4 years. Of two studies reporting progression in patients with nr-axSpA treated with TNFis, one showed no mSASSS progression; however, the lack of control limited comparative conclusions.

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Section: Discussionmentioning

confidence: 99%

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

Baraliakos

Gensler

D’Angelo³

et al. 2020

Therapeutic Advances in Musculoskeletal

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“…The second hypothesis, the “unfolded protein response”, suggests that HLA-B*27 tends to fold slowly and often misfolds. The misfolded HLA-B*27 molecules accumulate in the endoplasmic reticulum (ER), where they induce a stress response that leads to an unfolded protein response (UPR) and autophagy [ 22 , 23 , 24 ]. The upregulation of UPR genes subsequently activates the production of pro-inflammatory cytokines such as IL-17, IL-23, and IFN-γ [ 23 ].…”

Section: Models Of Spa Pathogenesis: Hypothesesmentioning

confidence: 99%

“…According to this hypothesis, HLA-B*27 heavy chains homodimerize at the cell surface, where they act as pro-inflammatory ligands for humoral or cell-mediated autoimmune responses [ 14 , 22 ]. These homodimers are capable of binding to certain killer cell immunoglobulin-like receptors (KIRs), which are expressed on natural killer cells and T cells, and this leads to the upregulation of the pro-inflammatory cytokine IL-17 [ 24 ].…”

Section: Models Of Spa Pathogenesis: Hypothesesmentioning

confidence: 99%

Understanding the Pathogenesis of Spondyloarthritis

Sharip

Kunz

2020

Biomolecules

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Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

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“…Ankylosing spondylitis is a chronic, immune-mediated, inflammatory condition within the family of spondyloarthritis (SpA) with several shared clinical, genetic, and immunologic features [1]. Active ankylosing spondylitis is characterized by inflammation at the sacroiliac joint and insertion sites of tendons and ligaments (i.e., enthesitis), as well as increased risk of fusion of the sacroiliac joint and spine [2,3]. Patients experience severe back pain, spinal stiffness, and reduced spinal mobility, which may lead to severe deformity (i.e., bamboo spine) in some.…”

Section: Introductionmentioning

confidence: 99%

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis

Deodhar

Chakravarty

Cameron³

et al. 2020

Clin Rheumatol

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Objective To compare the relative efficacy of current and investigational biologic and oral small molecule (OSM) treatments for active ankylosing spondylitis (AS). Methods A systematic literature review was conducted to identify all phase 2/3 randomized trials of interest in patients with AS. Outcomes assessed were ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) and C-reactive protein (CRP) at weeks 12-16. Bayesian network meta-analyses were conducted for outcomes using a random effects model. Baseline-risk adjustment was also conducted to account for differences in placebo response across studies. Surface Under the Cumulative Ranking curve (SUCRA) values are reported, reflecting the relative probability that intervention was the best of all interventions. Results The investigational agent tofacitinib 5 mg was the top-ranked treatment (SUCRA, 93%) for ASAS20 response, followed by intravenous (IV) golimumab 2 mg/kg (90%). Golimumab IV 2 mg/kg and infliximab 5 mg/kg were the top two ranked treatments for change from baseline in BASFI (golimumab IV, 81%; infliximab, 80%) and change from baseline in CRP (infliximab, 90%; golimumab IV, 82%). Conclusions Two approved therapies (golimumab IV, infliximab) and one investigational product ranked highest for efficacy in AS. Key Points • Although golimumab IV, infliximab, and tofacitinib ranked highest for efficacy in AS, differences in efficacy between approved and investigational therapies were not statistically significant.

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Recent advances in ankylosing spondylitis: understanding the disease and management

Cited by 99 publications

References 102 publications

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

Understanding the Pathogenesis of Spondyloarthritis

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis

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