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Rheumatology and Therapy Jun 2024This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of...
Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials.
INTRODUCTION
This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]).
METHODS
Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY).
RESULTS
A total of 1789 patients (PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (n = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases.
CONCLUSION
Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.
TRIAL REGISTRATION
SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.
PubMed: 38683479
DOI: 10.1007/s40744-024-00671-4 -
Rheumatology International Jun 2024Patients with axial spondyloarthritis (axSpA) benefit from regular home-based exercise (HbE). In spite of recommendations, a relevant proportion of German axSpA patients...
BACKGROUND
Patients with axial spondyloarthritis (axSpA) benefit from regular home-based exercise (HbE). In spite of recommendations, a relevant proportion of German axSpA patients does not adhere to recommended HbE practices. To enhance HbE care, we developed the novel digital therapeutic (DTx) "Axia" compliant with the European medical device regulation (MDR). Axia offers a modern app-based HbE solution with patient educative content and further integrated features.
OBJECTIVE
We aimed to assess Axia's efficacy, attractiveness, and functionality through a survey among axSpA-patients involved in the first user tests.
METHODS
A mixed-method online questionnaire with 38 items was administered to 37 axSpA volunteers after using Axia. Numeric rating scales (NRS) and likelihood scales were primarily used.
RESULTS
HbE frequency significantly increased from a median of 1 day/week to 6 days/week (p < 0.001) by using Axia. Existing HbE practitioners also increased their frequency (median of 4 days/week before, 6 days/week with Axia, p < 0.05). Axia received a median rating of 5 out of 5 stars. On NRS scales, Axia scored a median of 9 for intuitiveness and design, and a median of 8 for entertainment. 64.9% reported improved range of motion, 43.2% reported reduced pain, and 93.6% enhanced disease-specific knowledge. All users recommended Axia to other patients.
CONCLUSION
Axia increases axSpA patients HbE frequency, possibly due to its good intuitiveness and design, leading to reduction in pain and subjective improvement of range of motion. This warrants further investigation in large randomized controlled interventional trials to establish its efficacy conclusively and patients adherence to HbE.
Topics: Humans; Male; Female; Cross-Sectional Studies; Adult; Middle Aged; Exercise Therapy; Mobile Applications; Axial Spondyloarthritis; Surveys and Questionnaires; Patient Education as Topic; Germany; Patient Compliance
PubMed: 38683351
DOI: 10.1007/s00296-024-05600-w -
Journal of Orthopaedic Case Reports Apr 2024Ankylosing spondylitis is a spondyloarthropathy that commonly involves the axial skeleton with predilection to the sacro-iliac joints and spine. The disease frequently...
INTRODUCTION
Ankylosing spondylitis is a spondyloarthropathy that commonly involves the axial skeleton with predilection to the sacro-iliac joints and spine. The disease frequently results in a smooth globular kyphotic deformity of the spine; however, a coronal plane scoliotic deformity is extremely rare. We present a unique case of scoliotic deformity in a patient diagnosed with ankylosing spondylitis. To the best of our knowledge, following a review of the literature, this appears to be the first report of this kind.
CASE REPORT
A 23-year-old male patient presented with chronic back pain, stiffness, and a truncal shift of the body. He had a rigid left-sided thoracolumbar curve measuring 41° with a coronal imbalance of 3.6 cm. We present a case report on scoliosis deformity correction performed with a four-level asymmetric pontes osteotomy using a bone scalpel with excellent correction of the scoliotic deformity that was well maintained at 2-year follow-up.
CONCLUSION
Scoliosis in ankylosing spondylitis has not been documented in literature. We report the complete correction of the deformity, which is well maintained at the 2-year follow-up.
PubMed: 38681911
DOI: 10.13107/jocr.2024.v14.i04.4398 -
Cureus Mar 2024Ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) are common rheumatologic ailments that cause multiorgan system disease. The incidence of lupus and AS...
Ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) are common rheumatologic ailments that cause multiorgan system disease. The incidence of lupus and AS in the same patient is rare and has seldom been described in the literature. Comorbid lupus and AS provide interesting diagnostic and therapeutic challenges. Here, we present a case of comorbid lupus and AS, discuss the diagnostic challenges in diagnosing these conditions, and put forth possible therapeutic interventions that may benefit similar patients.
PubMed: 38681357
DOI: 10.7759/cureus.57080 -
Cureus Mar 2024Spondyloarthropathy (SpA) is one of the most common causes of low back pain. It is caused by inflammatory arthritis in the spine, manifesting in various forms such as... (Review)
Review
Spondyloarthropathy (SpA) is one of the most common causes of low back pain. It is caused by inflammatory arthritis in the spine, manifesting in various forms such as psoriatic arthritis (PsA), ankylosing spondylitis (AS), and sacroiliitis. A comprehensive systematic literature search was done to evaluate and compare MRI, CT, single-photon emission CT, PET, ultrasound (US) imaging, low-dose CT, and diffusion-weighted imaging (DWI) techniques in assessing SpAs. The search strategy was constructed by an analysis of key terms from relevant articles in MEDLINE ProQuest, Embase, and PubMed. The key terms used to search for these articles were "SpA," "sacroiliitis," "spondylitis," "psoriatic arthritis," "MRI," "CT scan," "x-ray," "magnetic resonance imaging," "computed tomography," "bone density," and "ultrasound." A total of 1,131 articles published in English between January 1, 2003, and October 15, 2023 were identified and screened for eligibility by members of the research team, which resulted in 69 total articles selected for the final review. US has played an important role in visualizing joint inflammation and enthesitis (inflammation of the enthesis), which are common features of PsA. Although MRI and CT are considered more reliable modalities for diagnosing active sacroiliitis, US imaging with Doppler flow can also be useful in conjunction with CT images to visualize abnormal blood flow in the sacroiliac joints, as well as other joints affected by inflammatory arthritis. MRI provides increased diagnostic confidence in the diagnosis of sacroiliitis in active AS patients when compared to CT. CT is more sensitive than plain radiographs. The PET activity score showed a good correlation in diagnosing inflammatory sacroiliitis but lacked in identifying structural lesions. CT has high diagnostic accuracy, but it exposes patients to a high radiation dose. MRI visualizes joint and tissue inflammation, bone, and bone marrow change and can identify peripheral inflammation in soft tissue and joints in patients diagnosed with PsA. MRI can also visualize bone marrow changes and subchondral edema, which can aid in the early diagnosis of ankylosing SpA and gauge disease severity. DWI and short-tau inversion recovery imaging are both MRI techniques used in detecting sacroiliitis. MRI and CT are shown to be reliable imaging modalities for the diagnosis of sacroiliitis; however, it was found that Doppler US played an accurate role in the diagnosis as well. MRI visualizes joints and tissue with the most precision, making it useful in evaluating patients with PsA, while PET CT is useful in the diagnosis of inflammatory sacroiliitis patients. There is limited literature available comparing the multiple modalities of imaging available for each SpA. The review's objective is to analyze imaging findings in patients diagnosed with sacroiliitis and SpAs. The findings in this literature review are valuable for properly assessing and diagnosing patients suffering from SpAs.
PubMed: 38681346
DOI: 10.7759/cureus.57185 -
Brain & Spine 2024Injuries to the rigid spine have a distinguished position in the broad spectrum of spinal injuries due to altered biomechanical properties. The rigid spine is more prone... (Review)
Review
Injuries to the rigid spine have a distinguished position in the broad spectrum of spinal injuries due to altered biomechanical properties. The rigid spine is more prone to fractures. Two ossification bone disorders that are of particular interest are Ankylosing Spondylitis (AS) and Diffuse Idiopathic Skeletal Hyperostosis (DISH). DISH is a non-inflammatory condition that leads to an anterolateral ossification of the spine. AS on the other hand is a chronic inflammatory disease that leads to cortical bone erosions and spinal ossifications. Both diseases gradually induce stiffening of the spine. The prevalence of DISH is age-related and is therefore higher in the older population. Although the prevalence of AS is not age-related the occurrence of spinal ossification is higher with increasing age. This association with age and the aging demographics in industrialized nations illustrate the need for medical professionals to be adequately informed and prepared. The aim of this narrating review is to give an overview on the diagnostic and therapeutic measures of the ankylosed spine. Because of highly unstable fracture configurations, injuries to the rigid spine are highly susceptible to neurological deficits. Diagnosing a fracture of the ankylosed spine on plain radiographs can be challenging. Moreover, since 8% of patients with ankylosing spine disorders (ASD) have multiple non-contagious fractures, a CT scan of the entire spine is highly recommended as the primary diagnostic tool. There are no consensus-based guidelines for the treatment of spinal fractures in ASD. The presence of neurological deficit or unstable fractures are absolute indications for surgical intervention. If conservative therapy is chosen, patients should be monitored closely to ensure that secondary neurologic deterioration does not occur. For the fractures that have to be treated surgically, stabilization of at least three segments above and below the fracture zone is recommended. These fractures mostly are treated via the posterior approach. Patients with AS or DISH share a significant risk for complications after a traumatic spine injury. The most frequent complications for patients with thoracolumbar burst fractures are respiratory failure, pseudoarthrosis, pneumonia, and implant failure.
PubMed: 38681176
DOI: 10.1016/j.bas.2024.102811 -
International Journal of Hyperthermia :... 2024Heat shock proteins (HSP) have been associated with a range of persistent inflammatory disorders; however, little research has been conducted on the involvement of HSP...
Heat shock proteins (HSP) have been associated with a range of persistent inflammatory disorders; however, little research has been conducted on the involvement of HSP in the development of ankylosing spondylitis (AS). The research aims to identify a diagnostic signature based on HSP-related genes and determine the molecular subtypes of AS. We gathered the transcriptional data of patients with AS from the GSE73754 dataset and conducted a literature search for HSP-related genes (HRGs). The logistic regression model was utilized for the identification of hub HRGs associated with AS. Subsequently, these HRGs were employed in the construction of a nomogram prediction model. We employed a consensus clustering approach to identify novel molecular subgroups. Subsequently, we conducted functional analyses, encompassing GO, KEGG, and GSEA, to elucidate the underlying mechanisms between these subgroups. To assess the immunological landscape, we employed the xCell algorithm. Through logistic regression analysis, the four core HRGs (CCT2, HSPA6, DNAJB14, and DNAJC5) were confirmed as potential biomarkers for AS. Subsequent stratification revealed two distinct molecular phenotypes, designated as Cluster 1 and Cluster 2. Notably, Cluster 2 was characterized by the upregulation of pathways pertinent to immune response and inflammation. Our research suggests that the CCT2, HSPA6, DNAJB14, and DNAJC5 exhibit potential as effective blood-based diagnostic biomarkers for AS. These findings contribute to a deeper comprehension of the underlying mechanisms involved in the development of AS and offer potential targets for personalized therapeutic interventions.
Topics: Humans; Spondylitis, Ankylosing; Heat-Shock Proteins
PubMed: 38679420
DOI: 10.1080/02656736.2024.2336149 -
Genes Mar 2024is the bacterium responsible for causing the zoonotic disease called anthrax. The disease presents itself in different forms like gastrointestinal, inhalation, and...
is the bacterium responsible for causing the zoonotic disease called anthrax. The disease presents itself in different forms like gastrointestinal, inhalation, and cutaneous. Bacterial spores are tremendously adaptable, can persist for extended periods and occasionally endanger human health. The Anthrax Toxin Receptor-2 () gene acts as membrane receptor and facilitates the entry of the anthrax toxin into host cells. Additionally, mutations in the gene have been linked to various autoimmune diseases, including Hyaline Fibromatosis Syndrome (HFS), Ankylosing Spondylitis (AS), Juvenile Hyaline Fibromatosis (JHF), and Infantile Systemic Hyalinosis (ISH). This study delves into the genetic landscape of , aiming to comprehend its associations with diverse disorders, elucidate the impacts of its mutations, and pinpoint minimal non-pathogenic mutations capable of reducing the binding affinity of the gene with the protective antigen. Recognizing the pivotal role of single-nucleotide polymorphisms (SNPs) in shaping genetic diversity, we conducted computational analyses to discern highly deleterious and tolerated non-synonymous SNPs (nsSNPs) in the gene. The Mutpred2 server determined that the Arg465Trp alteration in the gene leads to altered DNA binding ( = 0.22) with a probability of a deleterious mutation of 0.808; notably, among the identified deleterious SNPs, rs368288611 (Arg465Trp) stands out due to its significant impact on altering the DNA-binding ability of . We propose these SNPs as potential candidates for hypertension linked to the gene, which is implicated in blood pressure regulation. Noteworthy among the tolerated substitutions is rs200536829 (Ala33Ser), recognized as less pathogenic; this highlights its potential as a valuable biomarker, potentially reducing side effects on the host while also reducing binding with the protective antigen protein. Investigating these SNPs holds the potential to correlate with several autoimmune disorders and mitigate the impact of anthrax disease in humans.
Topics: Antigens, Bacterial; Humans; Anthrax; Receptors, Peptide; Mutation; Polymorphism, Single Nucleotide; Bacterial Toxins; Bacillus anthracis; Hyaline Fibromatosis Syndrome; Spondylitis, Ankylosing; Disease Resistance; Receptors, Cell Surface; Protein Binding
PubMed: 38674361
DOI: 10.3390/genes15040426 -
Medicina (Kaunas, Lithuania) Mar 2024: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from...
: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. : This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. : The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. : Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.
Topics: Humans; Male; Female; Adult; Middle Aged; Republic of Korea; Spondylarthritis; Incidence; Tuberculosis; Mycobacterium Infections, Nontuberculous; Aged; Cohort Studies; Arthritis, Psoriatic; Spondylitis, Ankylosing
PubMed: 38674225
DOI: 10.3390/medicina60040579 -
Journal of Personalized Medicine Apr 2024(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2)...
(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug.
PubMed: 38673044
DOI: 10.3390/jpm14040417