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International Journal of Nanomedicine 2019Ankylosing spondylitis (AS) is a complex disease characterized by inflammation and ankylosis primarily at the cartilage-bone interface. The disease is more common in... (Review)
Review
Ankylosing spondylitis (AS) is a complex disease characterized by inflammation and ankylosis primarily at the cartilage-bone interface. The disease is more common in young males and risk factors include both genetic and environmental. While the pathogenesis of AS is not completely understood, it is thought to be an immune-mediated disease involving inflammatory cellular infiltrates, and human leukocyte antigen-B27. Currently, there is no specific diagnostic technique available for this disease; therefore conventional diagnostic approaches such as clinical symptoms, laboratory tests and imaging techniques are used. There are various review papers that have been published on conventional treatment approaches, and in this review work, we focus on the more promising nanomedicine-based treatment modalities to move this field forward.
Topics: Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Female; Humans; Hydrogels; Liposomes; Male; Nanomedicine; Nanoparticles; Physical Therapy Modalities; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha
PubMed: 31806960
DOI: 10.2147/IJN.S216199 -
Current Opinion in Rheumatology Jul 2023For almost a decade, treat-to-target (T2T) has been advocated as a management strategy for axial spondyloarthritis (axSpA), despite a lack of trial evidence. Recently,... (Review)
Review
PURPOSE OF REVIEW
For almost a decade, treat-to-target (T2T) has been advocated as a management strategy for axial spondyloarthritis (axSpA), despite a lack of trial evidence. Recently, the first and only published T2T trial in axSpA did not meet its primary endpoint. The purpose of this review is to discuss whether we should continue with a T2T approach in axSpA and to describe some experiences with T2T in clinical practice.
RECENT FINDINGS
The trial showed no superiority of T2T compared with usual care; however, several secondary trial outcomes and the health economic analysis actually favoured T2T, and there are conceivable reasons for the negative trial results. Furthermore, several knowledge gaps related to an optimal T2T approach in axSpA were identified. In clinical practice, a T2T approach was applied to only a limited extent, possibly because of several challenges.
SUMMARY
Despite one negative trial, it is too early to abandon T2T in axSpA. Not only more evidence from clinical trials but also research on the optimal target and management of all facets of axSpA, are highly needed. For successful implementation of T2T in clinical practice, it is important that barriers and facilitators to application are identified and subsequently addressed.
Topics: Humans; Spondylarthritis; Axial Spondyloarthritis
PubMed: 37071063
DOI: 10.1097/BOR.0000000000000941 -
Current Opinion in Rheumatology Jul 2021Axial spondyloarthritis (axSpA) affects 0.5-1% of the population in many regions of the world. This review summarizes the challenges in medical education around axSpA... (Review)
Review
PURPOSE OF REVIEW
Axial spondyloarthritis (axSpA) affects 0.5-1% of the population in many regions of the world. This review summarizes the challenges in medical education around axSpA with attention to evidence around delayed diagnosis, clinician familiarity with typical axSpA features, such as inflammatory back pain and adherence to accepted management principles.
RECENT FINDINGS
Clinicians who commonly manage patients with chronic back pain or other typical axSpA features are not consistently aware of the concept of inflammatory back pain and common extra-spinal manifestations. Further, clinicians may not be familiar with the nonradiographic spectrum of axSpA. Management of patients with possible axSpA does not consistently follow principles that would establish an axSpA diagnosis, and diagnosis of axSpA remains delayed by 6-7 years on average, with evidence suggesting management disparities on the basis of sex and race in some cases. Referral recommendations have increased the probability of axSpA diagnosis up to about 40% and, may complement educational efforts in axSpA.
SUMMARY
Educational efforts in axSpA should focus on providing front-line clinicians with a better understanding of inflammatory back pain, the nonradiographic form of axSpA, and accepted principles in axSpA management.
Topics: Humans; Pain; Referral and Consultation; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 33973547
DOI: 10.1097/BOR.0000000000000806 -
F1000Research 2020Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that predominantly affects the axial skeleton. The advent of biologic drugs has transformed... (Review)
Review
Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that predominantly affects the axial skeleton. The advent of biologic drugs has transformed the management of patients with axSpA. However, non-steroidal anti-inflammatory drugs remain the first-line drug treatment for axSpA. The optimal management of patients with axSpA requires a combination of pharmacological and non-pharmacological treatment modalities, namely exercise and physical therapy. This review looks at novel therapeutic options in patients with axSpA. It also summarises current evidence regarding radiographic progression and treat-to-target in axSpA.
Topics: Disease Progression; Humans; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 32704350
DOI: 10.12688/f1000research.22577.1 -
Annals of the Rheumatic Diseases Jan 2024Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in... (Randomized Controlled Trial)
Randomized Controlled Trial
Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies.
OBJECTIVES
Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52.
METHODS
BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks.
RESULTS
Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%).
CONCLUSIONS
At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ.
TRIAL REGISTRATION NUMBER
NCT03928704; NCT03928743.
Topics: Humans; Interleukin-17; Non-Radiographic Axial Spondyloarthritis; Treatment Outcome; Spondylitis, Ankylosing; Spondylarthritis; Double-Blind Method; Antibodies, Monoclonal, Humanized
PubMed: 37793792
DOI: 10.1136/ard-2023-224803 -
The American Journal of Pathology May 2022Pathologic soft tissue calcification can occur in both genetic and acquired clinical conditions, causing significant morbidity and mortality. Although the... (Review)
Review
Pathologic soft tissue calcification can occur in both genetic and acquired clinical conditions, causing significant morbidity and mortality. Although the pathomechanisms of pathologic calcification are poorly understood, major progress has been made in recent years in defining the underlying genetic defects in Mendelian disorders of ectopic calcification. This review presents an overview of the pathophysiology of five monogenic disorders of pathologic calcification: pseudoxanthoma elasticum, generalized arterial calcification of infancy, arterial calcification due to deficiency of CD73, ankylosis, and progeria. These hereditary disorders, caused by mutations in genes encoding ATP binding cassette subfamily C member 6, ectonucleotide pyrophosphatase/phosphodiesterase 1, CD73, progressive ankylosis protein, and lamin A/C proteins, respectively, are inorganic pyrophosphate (PPi) deficiency syndromes with reduced circulating levels of PPi, the principal physiologic inhibitor of calcium hydroxyapatite deposition in soft connective tissues. In addition to genetic diseases, PPi deficiency has been encountered in acquired clinical conditions accompanied by pathologic calcification. Because specific and effective treatments are lacking for pathologic calcification, the unifying finding of PPi deficiency suggests that PPi-targeted therapies may be beneficial to counteract pathologic soft tissue calcification in both genetic and acquired diseases.
Topics: Ankylosis; Calcinosis; Choristoma; Diphosphates; Humans; Pseudoxanthoma Elasticum; Syndrome; Vascular Calcification
PubMed: 35182493
DOI: 10.1016/j.ajpath.2022.01.012 -
Mayo Clinic Proceedings Jan 2022Axial spondyloarthritis (axSpA) is a chronic, immune-mediated inflammatory disease characterized by inflammatory low back pain, inflammation in peripheral joints and... (Review)
Review
Axial spondyloarthritis (axSpA) is a chronic, immune-mediated inflammatory disease characterized by inflammatory low back pain, inflammation in peripheral joints and entheses, and other extra-articular or systemic manifestations. Although our understanding of the natural history of axSpA has been limited by incomplete knowledge of disease pathogenesis, axSpA is increasingly understood as a spectrum of axial, peripheral, and extra-articular inflammatory conditions that includes nonradiographic axSpA and radiographic axSpA, also known as ankylosing spondylitis. In this narrative review, we present a road map of this axSpA continuum, highlighting genetic risk factors for the development of axSpA, triggers of disease, and reasons for and implications of diagnostic delay. We present a detailed overview of the spectrum of axSpA clinical manifestations and highlight factors known to influence the risk of disease progression. Finally, we provide some expert commentary on the practical use of this road map to assist health care providers in the identification of axSpA in clinical practice.
Topics: Delayed Diagnosis; Disease Progression; Female; Humans; Male; Non-Radiographic Axial Spondyloarthritis; Risk Factors; Spondylitis, Ankylosing
PubMed: 34801248
DOI: 10.1016/j.mayocp.2021.08.007 -
The Journal of International Medical... Nov 2020To comprehensively review the literature and summarize the results from human and animal studies related to the possible causes and pathogenesis of traumatic... (Review)
Review
OBJECTIVE
To comprehensively review the literature and summarize the results from human and animal studies related to the possible causes and pathogenesis of traumatic temporomandibular joint ankylosis (TMJA).
MATERIALS AND METHODS
The Google Scholar, Embase, and Web of Science databases were used to search for articles related to traumatic TMJA from 2011 to 2020. All articles were screened according to the inclusion and exclusion criteria, collected, and analyzed.
RESULTS
Nineteen relevant articles were collected. These articles were classified into three groups: predisposing and etiological factors, cellular studies, and molecular studies.
CONCLUSION
The pathological mechanisms are similar between TMJA and nonunion hypertrophy. Aberrant structural and etiological factors as well as disordered cellular and molecular mechanisms might contribute to TMJA formation. Although preclinical and clinical data have provided new evidence on the pathogenesis of traumatic TMJA, the molecular mechanisms and biological events require further exploration.
Topics: Animals; Ankylosis; Humans; Temporomandibular Joint; Temporomandibular Joint Disorders
PubMed: 33213251
DOI: 10.1177/0300060520972073 -
Missouri Medicine 2022Understanding of the spondyloarthritis diseases has changed significantly in the last 15 years. It is now clear that there are patients with and without radiographic...
Understanding of the spondyloarthritis diseases has changed significantly in the last 15 years. It is now clear that there are patients with and without radiographic changes and the terminology has changed to reflect that: radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis. In addition, the importance of the presence of inflammatory back pain with spondyloarthritis in making the diagnosis is now well established. It is also clear that women are much more likely to develop axial spondyloarthritis than previously thought. Finally, there are treatments now available to treat axial spondyloarthritis and more hopefully to be approved in the next year.
Topics: Axial Spondyloarthritis; Female; Humans; Pain; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 36033135
DOI: No ID Found -
Scientific Reports Feb 2022Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been...
Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rβ- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear β-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on β-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.
Topics: Animals; Ankylosis; Becaplermin; Core Binding Factor Alpha 1 Subunit; Periodontal Ligament; Proto-Oncogene Proteins c-sis; RNA, Messenger; Rats; Tooth Ankylosis; Tooth Replantation; beta Catenin
PubMed: 35217688
DOI: 10.1038/s41598-022-06865-6