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RMD Open Jul 2023The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in...
The 2023 pipeline of disease-modifying antirheumatic drugs (DMARDs) in clinical development for spondyloarthritis (including psoriatic arthritis): a systematic review of trials.
OBJECTIVES
The objective of this systematic review was to provide an overview of current developments and potentially available therapeutic options for spondyloarthritis (SpA) in the coming years.
METHODS
We conducted a systematic review of 17 national and international clinical trial databases for all disease-modifying antirheumatic drugs (DMARDs) for SpA that are already marketed, in clinical development or withdrawn. The search was performed on February 2023 with the keywords "spondyloarthritis", "ankylosing spondylitis" and "psoriatic arthritis". For each molecule, we only considered the study at the most advanced stage of clinical development.
RESULTS
Concerning axial SpA (axSpA), a total of 44 DMARDs were identified: 6 conventional synthetic DMARDs (csDMARDs), 27 biological DMARDs (bDMARDs) and 11 targeted synthetic DMARDs (tsDMARDs). Among the 18 targeted treatments (b+tsDMARDs) in current development, corresponding trials reached phase I (n=1), II (n=10) and III (n=7). Ten molecules are IL-17 inhibitors, two Janus kinase (JAK) inhibitors and two granulocyte-macrophage colony-stimulating factor inhibitors; four have another mode of action. Concerning psoriatic arthritis (PsA), 44 DMARDs were identified: 5 csDMARDs, 27 bDMARDs and 12 tsDMARDs. Among the 15 molecules in current development, corresponding trials reached phase II (n=8) and III (n=7). Six molecules are JAK inhibitors, six IL-17 inhibitors and one an IL-23 inhibitor; two have another mode of action.
CONCLUSION
This systematic review identified 18 and 15 molecules in clinical development for axSpA and PsA, respectively, which suggests a strengthening of the therapeutic arsenal in the coming years. However, with so many DMARDs but low target diversity, we will need to develop strategies or biomarkers to help clinicians make informed treatment decisions.
Topics: Humans; Arthritis, Psoriatic; Antirheumatic Agents; Interleukin-17; Spondylarthritis; Spondylitis, Ankylosing; Janus Kinase Inhibitors
PubMed: 37507210
DOI: 10.1136/rmdopen-2023-003279 -
Advances in Rheumatology (London,... Jul 2023Ankylosing Spondylitis (AS) patients face several challenges due to the nature of the disease and its physical and psychological complications. Sleep disorders are among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ankylosing Spondylitis (AS) patients face several challenges due to the nature of the disease and its physical and psychological complications. Sleep disorders are among the most important concerns. Sleep disorders can aggravate the signs and symptoms of the disease and ultimately reduce the quality of patients' lives. This study uses a systematic review and meta-analysis to pool the reported prevalence of sleep disorders among AS patients.
METHODS
To find related studies, the WoS, PubMed, ScienceDirect, Scopus, Embase, and Google Scholar databases were systematically searched without a lower time limit. Heterogeneity among the identified studies was checked using the I index, and the Begg and Mazumdar correlation test examined the existence of published bias. Comprehensive Meta-Analysis (v.2) software was adopted to analyze the data.
RESULTS
In the review of 18 studies with a sample size of 5,840, the overall pooled prevalence of sleep disorders among AS patients based on the random effects method was found to be 53% (95% CI: 44.9-61). The highest and lowest prevalence was in Egypt at 90% and Australia at 19.2%, respectively. Our meta-regression results show that with the increase in 'sample size' and 'year of publication', the overall prevalence of sleep disorders in patients with AS decreases (p < 0.05).
CONCLUSION
The results of the present study indicate a high and significant prevalence of sleep disorders among AS patients. Thus, health policymakers and healthcare providers must focus on timely diagnosis and effective educational and therapeutic interventions for the prevention and proper treatment of sleep disorders in this population of patients.
Topics: Humans; Spondylitis, Ankylosing; Prevalence; Sleep Wake Disorders; Sleep; Egypt
PubMed: 37468951
DOI: 10.1186/s42358-023-00315-1 -
Clinical Rheumatology Oct 2023Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of... (Review)
Review
Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.
Topics: Male; Humans; Female; Spondylarthritis; Cardiovascular Diseases; Artificial Intelligence; Risk Factors; Spondylitis, Ankylosing; Heart Disease Risk Factors
PubMed: 37418034
DOI: 10.1007/s10067-023-06655-z -
Clinical Rheumatology Sep 2023C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
C-reactive protein (CRP) and magnetic resonance imaging (MRI) are widely used to monitor inflammation in patients with axial spondyloarthritis (axSpA), but the relationship between CRP and MRI-detected inflammation is incompletely understood. The present study was undertaken to assess correlations between CRP and MRI-detected inflammation in axSpA.
MATERIALS AND METHODS
A systematic literature search was performed (Medline, Embase, and Cochrane Library) to identify relevant studies concerning CRP and MRI-detected inflammation in axSpA patients. The MRI-detected inflammation was evaluated by MRI-based disease activity score (DAS). The correlation between CRP and MRI-based DAS was integrated by random-effect models.
RESULTS
Eighteen studies reported a total of 1392 axSpA patients which were included in this meta-analysis. CRP was significantly associated with spinal MR DAS (r=0.226, 95%CI [0.149, 0.291], p<0.001, I=23%). We also found a moderate correlation between CRP change and spinal MR DAS change (r[ASspiMRI-a]=0.354, 95%CI [0.282, 0.422], p<0.001, I=48%; r[SPARCC]=0.544, 95%CI [0.345, 0.701], p<0.001, I=19%). CRP at baseline was negatively associated with improvement in spinal MR DAS (r= - 0.327, 95%CI [-0.397, -0.264], p<0.001, I=0%). However, no significant association was found between CRP and sacroiliac joint (SIJ) MR DAS.
CONCLUSIONS
In axSpA patients, CRP is associated with MRI-detected inflammation in the spine but not in SIJ. We speculate that CRP could be a reasonable index to reflect spinal inflammation. Therefore, we suggest it is not essential to repeat spinal MRI in a short term, while SIJ MRI may be necessary to provide additional information on inflammation. Key Points • CRP is associated with MRI-detected inflammation in the spine but not in sacroiliac joints. • CRP at baseline was negatively associated with improvement in spinal MR DAS. • It was not essential to repeat spinal MRI frequently, while SIJ MRI may be necessary to provide additional information on inflammation.
Topics: Humans; C-Reactive Protein; Spondylarthritis; Inflammation; Sacroiliac Joint; Magnetic Resonance Imaging; Axial Spondyloarthritis
PubMed: 37336841
DOI: 10.1007/s10067-023-06658-w -
Journal of Neurosurgery. Spine Sep 2023The goal in this study was to compare the efficacy and safety outcomes of vertebral column decancellation (VCD) and pedicle subtraction osteotomy (PSO) for patients with... (Meta-Analysis)
Meta-Analysis
Comparison of pedicle subtraction osteotomy and vertebral column decancellation for the correction of thoracolumbar kyphotic deformity in ankylosing spondylitis: a systematic review and meta-analysis.
OBJECTIVE
The goal in this study was to compare the efficacy and safety outcomes of vertebral column decancellation (VCD) and pedicle subtraction osteotomy (PSO) for patients with ankylosing spondylitis (AS) with thoracolumbar kyphotic deformity.
METHODS
This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO). The authors conducted a computer search of PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Wei Pu Database to collect controlled clinical studies on the efficacy and safety of VCD and PSO for patients with AS with thoracolumbar kyphotic deformity. The search covered the period from database establishment to March 2023. Two researchers screened the literature, extracted data, and evaluated the risk of bias of the included studies; these researchers recorded the authors and the sample size, and they extracted data on the intraoperative blood loss, Oswestry Disability Index, spine sagittal parameters, operation time, and complications in each study. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library.
RESULTS
A total of 6 cohort studies with a total of 342 patients were included in this study, including 172 patients in the VCD group and 170 patients in the PSO group. The VCD group had lower intraoperative blood loss than the PSO group (mean difference [MD] -274.92, 95% CI -506.63 to -43.20, p = 0.02); significant correction of the sagittal vertical axis compared with the PSO group (MD 7.32, 95% CI -1.24 to 15.87, p = 0.03), and the operation time was shorter than that of the PSO group (MD -80.28, 95% CI -150.07 to -10.48, p = 0.02).
CONCLUSIONS
This systematic review and meta-analysis showed that VCD had more advantages than PSO in correcting the sagittal imbalance in the treatment of AS with thoracolumbar kyphotic deformity, and VCD had less intraoperative blood loss, shorter operation time, and satisfactory results in improving the quality of life.
Topics: Humans; Spondylitis, Ankylosing; Blood Loss, Surgical; Quality of Life; Lumbar Vertebrae; Treatment Outcome; Osteotomy; Kyphosis
PubMed: 37209071
DOI: 10.3171/2023.4.SPINE23329 -
The Journal of Evidence-based Dental... Jun 2023Clear evidence is lacking regarding the outcomes of autogenous tooth transplantation (ATT) of third molars with complete root formation. The current review aims to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Clear evidence is lacking regarding the outcomes of autogenous tooth transplantation (ATT) of third molars with complete root formation. The current review aims to explore the long-term survival and complication rates.
METHODS
A comprehensive search was performed in December 2022 of the PubMed, Scopus, Embase, EBSCO, Ovid, Science Direct, and Web of Science databases. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at the International Prospective Register of Systematic Reviews (CRD42022337659). The pooled survival, root resorption, and ankyloses rates were calculated. Subgroup analyses were performed to explore the effects of sample size and 3D techniques.
RESULTS
Twelve studies from 5 countries fulfilled the eligibility, with 759 third molars transplanted in 723 patients. Five studies reported 100% survival at 1-year follow-up. After excluding these 5 studies, the pooled survival rate was 93.62% at 1 year. The survival rate of 1 large sample study was significantly higher than that of small ones at 5 years. The complications of studies using 3D techniques were: root resorption 2.06% (95% CI: 0.22, 7.50) and ankyloses 2.81% (95% CI: 0.16, 12.22), compared to those without 3D techniques: root resorption 10.18% (95% CI: 4.50, 17.80) and ankyloses 6.49% (95% CI: 3.45, 10.96).
CONCLUSIONS
ATT of third molars with complete root formation is a reliable alternative for replacement of a missing tooth and has a promising survival rate. The use of 3D techniques can reduce complication rates and improve long-term survival.
Topics: Humans; Molar, Third; Root Resorption; Transplantation, Autologous; Ankylosis
PubMed: 37201977
DOI: 10.1016/j.jebdp.2023.101842 -
Autoimmunity Reviews Jul 2023Overweight and/or obese patients with inflammatory arthritis (IA) have higher disease activity and lower chances of achieving and/or maintaining the treatment targets.... (Review)
Review
Effect of body mass index on treatment response of biologic/targeted-synthetic DMARDs in patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis. A systematic review.
BACKGROUND
Overweight and/or obese patients with inflammatory arthritis (IA) have higher disease activity and lower chances of achieving and/or maintaining the treatment targets. Weight/obesity also appears to negatively affect the response to tumor necrosis factor (TNF) inhibitors in IA patients, including rheumatoid arthritis -RA, psoriatic arthritis -PsA, axial spondyloarthritis -AxSpA. We conducted a systematic literature review (SLR) for the effect of weight/body-mass-index (BMI) in the efficacy of all approved biologic (b) and targeted-synthetic (ts) DMARDs for the treatment of IA.
METHODS
For this PROSPERO-registered SLR, we searched PubMed, Scopus and Cohrane-Library from inception up to June 21st 2022. Clinical-trials (randomized and non-randomized) and observational studies of RA, PsA or AxSpA patients that reported the effect of weight/BMI on response (all possible outcomes) to b/ts-DMARDs were included. Risk-of-bias was assessed via RoB2-Cochrane-tool and Newcastle-Ottawa-scale for randomized and non-randomized studies, respectively.
FINDINGS
Out of 996 references, 75 eventually fulfilled the inclusion criteria (of which 10 studies were retrieved through manual-search). Among the included studies (TNF-inhibitors: 34, IL-12/23 inhibitors: 4, IL-23 inhibitor: 1, IL-17 inhibitors: 7, tocilizumab: 18, abatacept: 8, rituximab: 3, JAK-inhibitors: 5), most had medium RoB. Efficacy of TNF-inhibitors was affected by BMI in all forms of IA. Data are not robust to compare the effect among various TNF-inhibitors. In contrast, favorable results of IL-23 and IL-17 inhibitors did not appear to be influenced by increased BMI in PsA or AxSpA patients. Similar evidence exists for tocilizumab (in RA) and for abatacept (in RA and PsA), while no conclusion can be drawn for rituximab. More data are needed for JAK-inhibitors, although the effect of weight/BMI does not seem to be significant so far.
INTERPRETATION
Weight/BMI should be considered in the treatment-plan of IA patients, with its effect being more pronounced for TNF-inhibitors compared to other b/ts-DMARDs.
Topics: Humans; Arthritis, Psoriatic; Interleukin-17; Body Mass Index; Abatacept; Rituximab; Antirheumatic Agents; Arthritis, Rheumatoid; Axial Spondyloarthritis; Biological Products; Interleukin-23
PubMed: 37150489
DOI: 10.1016/j.autrev.2023.103357 -
Journal of Maxillofacial and Oral... Jun 2023Temporomandibular joint ankylosis is a disabling condition which affects joint movements causing difficulty in speech, mastication and hygiene. Over time various... (Review)
Review
BACKGROUND
Temporomandibular joint ankylosis is a disabling condition which affects joint movements causing difficulty in speech, mastication and hygiene. Over time various interposition materials like meniscus, muscle, fascia, skin, cartilage, fat, dura and alloplastic materials have been used for the treatment of ankylosis and improve joint functions.
OBJECTIVE
The objective of this systematic review is to evaluate the effectiveness of dermis fat graft and temporalis myofascial flap as an interpositional material in treatment of temporomandibular joint ankylosis and to compare the effectiveness of the two materials.
MATERIALS AND METHODS
PubMed, Google scholar, and Cochrane library search in combination with hand search of relevant journals were conducted published in English from January 2000 to August 2021. Randomized controlled trials, prospective and retrospective cohort studies were included. Outcome measure included improvement in mouth opening. Risk of bias assessment was assessed using Cochrane risk of bias tool and Newcastle-Ottawa scale.
RESULTS
A total of 144 articles were found from the primary search which on thorough assessment, duplicate and exclusion removal resulted in 9 cohort studies and 1 randomized controlled trial that fulfilled the inclusion criteria. All the studies included reported significant improvement in mouth opening after interposition of the 2 materials. Four studies compared temporalis myofascial flap with dermis fat graft, 2 studies reported dermis fat graft gives better outcomes, whereas 1 study reported temporalis myofascial flap to be better and 1 study has been inconclusive.
CONCLUSION
Definitive conclusions cannot be drawn as there are number of limitations in the studies included. However a general consensus has been toward dermis fat graft owing to fewer complications.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12663-023-01869-9.
PubMed: 37122786
DOI: 10.1007/s12663-023-01869-9 -
BMC Musculoskeletal Disorders Mar 2023Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the...
BACKGROUND
Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene.
CASE PRESENTATION
A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease.
CONCLUSION
We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.
Topics: Male; Humans; Child, Preschool; GTP-Binding Protein alpha Subunits, Gs; Rare Diseases; Ossification, Heterotopic; Myositis Ossificans; Exons; Mutation; Chromogranins
PubMed: 37003989
DOI: 10.1186/s12891-023-06371-4 -
Children (Basel, Switzerland) Mar 2023Infraocclusion of deciduous molars is a clinical disturbance that occurs during primary and mixed dentition and has some orthodontic implications. Infraoccluded teeth... (Review)
Review
BACKGROUND
Infraocclusion of deciduous molars is a clinical disturbance that occurs during primary and mixed dentition and has some orthodontic implications. Infraoccluded teeth are believed to be potential sites of malocclusion, with a risk of tipping neighbouring teeth and losing space. This systematic review aims to analyse the management of primary molars infraocclusion and to provide updated guidelines.
METHODS
A literature search was performed using PubMed, Scopus, and Web of Science databases from 1 January 2017 to 28 November 2022. The inclusion criteria were: studies only on human subjects, open access studies, case reports, randomised trials, retrospective, observational studies, and English language.
RESULTS
A total of 372 publications were identified from the databases and a final number of nine studies were included in the review for qualitative analysis.
CONCLUSION
Management of patients suffering from infraocclusion depends on the severity, age at diagnosis, and presence of succeeded premolars. Early diagnosis of infraoccluded primary elements is fundamental and cannot be postponed. Preservation of the primary molars may be a valid option with long-term stability if there is no or moderate primary molar infraocclusion, root resorption of less than half of the root, and no decay or restoration.
PubMed: 36980140
DOI: 10.3390/children10030582