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Cureus May 2024Rheumatoid arthritis (RA) is a complex autoimmune disease causing chronic joint inflammation and, in more serious cases, organ involvement. RA typically affects people... (Review)
Review
Rheumatoid arthritis (RA) is a complex autoimmune disease causing chronic joint inflammation and, in more serious cases, organ involvement. RA typically affects people between the ages of 35 and 60; however, it can also afflict children younger than the age of 16 years and can also demonstrate a pattern of remission later in the disease course. Non-steroidal anti-inflammatory drugs, glucocorticoids, exercise, and patient education are all used in the management of RA, which is divided into symptomatic management and disease-modifying management (disease-modifying antirheumatic drugs) to reduce pain and inflammation, thereby preserving joint function. Janus kinase inhibitors (JAKis) have led to a substantial improvement in the management of RA. By specifically targeting the JAK-signal transducer and activator of transcription pathway, which is essential for immunological modulation, these inhibitors also demonstrate promise in treating various autoimmune illnesses, including inflammatory bowel diseases, giant cell arteritis, ankylosing spondylitis, and psoriatic arthritis. Tofacitinib, baricitinib, upadacitinib, peficitinib, delgocitinib, and filgotinib are examples of FDA-approved JAKis that have distinct properties and indications for treating a range of autoimmune illnesses. JAKis demonstrate a promising treatment approach for managing RA and other autoimmune diseases while enhancing patient outcomes and quality of life. However, due to major safety concerns and the need for long-term success, meticulous patient monitoring is essential.
PubMed: 38854342
DOI: 10.7759/cureus.59978 -
Rheumatology and Therapy Jun 2024Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody...
Pharmacokinetics, Safety, and Immunogenicity of Intravenous and Subcutaneous Single-Dose QX002N Injection in Healthy Subjects: A Randomized, Open, Parallel, Single-Center, Phase I Study.
INTRODUCTION
Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies.
METHODS
A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay.
RESULTS
Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (C) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUC) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUC) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%.
CONCLUSIONS
Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects.
TRIAL REGISTRATION
www.chinadrugtirals.org.cn , CTR20220430.
PubMed: 38853228
DOI: 10.1007/s40744-024-00683-0 -
Seminars in Arthritis and Rheumatism Aug 2024To examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing...
OBJECTIVE
To examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing spondylitis (AS) patients.
METHODS
AS patients were retrospectively selected from a territory-wide database between 2006 and 2015, and were followed until the end of 2018. The primary outcome was the first occurrence of MACE. Multivariate time-varying Cox proportional hazard models were used to determine the associations between inflammatory burden (measured by c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and different therapies with incident MACE, after adjusting for traditional cardiovascular (CV) risk factors.
RESULTS
A total of 3827 patients with AS (mean age: 45.2 ± 15.0 years, male: 2911 [76.1 %]) were recruited. After a follow-up of 23,275 person-years, 135 patients (3.5 %) developed a first MACE. Univariate analyses showed that elevated ESR and CRP levels, and the use of glucocorticoids were associated with a significantly higher risk of MACE, while the use of sulfasalazine (SLZ), biologic DMARDs and non-cyclooxygenase-2 inhibitors (non-COX-IIi) were associated with reduced risk of MACE. After adjusting for CV risk factors in the multivariable models, only ESR (HR: 1.02; ESR ≥30 mm/h, HR:1.94) and CRP level (HR: 1.14; CRP >3 mg/dl HR:5.43) remained significantly associated with increased risk of MACE, while SLZ use (HR: 0.41-0.52) was protective against MACE.
CONCLUSION
High inflammatory burden was an independent predictor associated with an increased risk of MACE, while the use of SLZ might reduce risk of incident MACE in patients with AS.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Middle Aged; Adult; Cardiovascular Diseases; Incidence; Retrospective Studies; Antirheumatic Agents; Inflammation; Anti-Inflammatory Agents; C-Reactive Protein; Blood Sedimentation; Risk Factors
PubMed: 38852501
DOI: 10.1016/j.semarthrit.2024.152477 -
Best Practice & Research. Clinical... Jun 2024The gut microbiota plays a pivotal role in regulating host immunity, and dysregulation of this interaction is implicated in autoimmune and inflammatory diseases,... (Review)
Review
The gut microbiota plays a pivotal role in regulating host immunity, and dysregulation of this interaction is implicated in autoimmune and inflammatory diseases, including spondyloarthritis (SpA). This review explores microbial dysbiosis and altered metabolic function observed in various forms of SpA, such as ankylosing spondylitis (AS), psoriatic arthritis (PsA), acute anterior uveitis (AAU), and SpA-associated gut inflammation. Studies on animal models and clinical samples highlight the association between gut microbial dysbiosis, metabolic perturbations and immune dysregulation in SpA pathogenesis. These studies have received impetus through next-generation sequencing methods, which have enabled the characterization of gut microbial composition and function, and host gene expression. Microbial/metabolomic studies have revealed potential biomarkers and therapeutic targets, such as short-chain fatty acids, and tryptophan metabolites, offering insights into disease mechanisms and treatment approaches. Further studies on microbial function and its modulation of the immune response have uncovered molecular mechanisms underlying various SpA. Understanding the complex interplay between microbial community structure and function holds promise for improved diagnosis and management of SpA and other autoimmune disorders.
PubMed: 38851970
DOI: 10.1016/j.berh.2024.101961 -
Rheumatology (Oxford, England) Jun 2024To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial...
OBJECTIVE
To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations.
METHODS
Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat.
RESULTS
214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7.
CONCLUSION
Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations.
CLINICAL TRIAL REGISTER NUMBER
Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).
PubMed: 38851879
DOI: 10.1093/rheumatology/keae323 -
RMD Open Jun 2024To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial...
OBJECTIVES
To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA).
METHODS
Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account.
RESULTS
Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6-2.4)).
CONCLUSIONS
FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA.
Topics: Humans; Female; Male; Middle Aged; Magnetic Resonance Imaging; Ankylosis; Adult; Follow-Up Studies; Axial Spondyloarthritis; Inflammation; Zygapophyseal Joint; Spondylitis, Ankylosing; Radiography
PubMed: 38851237
DOI: 10.1136/rmdopen-2024-004199 -
RMD Open Jun 2024The International Map of Axial Spondyloarthritis (IMAS) is a global initiative aimed to assess the impact and burden of axial spondyloarthritis (axSpA) and identify the...
BACKGROUND
The International Map of Axial Spondyloarthritis (IMAS) is a global initiative aimed to assess the impact and burden of axial spondyloarthritis (axSpA) and identify the unmet needs from the patient's perspective.
METHOD
IMAS is a collaboration between the Axial Spondyloarthritis International Federation (ASIF), the University of Seville, Novartis Pharma AG and steered by a scientific committee. IMAS collected information through an online cross-sectional survey (2017-2022) from unselected patients with axSpA from Europe, Asia, North America, Latin America and Africa who completed a comprehensive questionnaire containing over 120 items.
RESULTS
5557 patients with axSpA participated in IMAS. Mean age was 43.9 ±12.8 years, 55.4% were female, 46.2% had a university education and 51.0% were employed. The mean diagnostic delay was 7.4 ±9.0 years (median: 4.0), and the mean symptom duration was 17.1 ±13.3 years. 75.0% of patients had active disease (Bath Ankylosing Spondylitis Disease Activity Index ≥4), and 59.4% reported poor mental health (12-item General Health Questionnaire ≥3). In the year before the survey, patients had visited primary care physicians 4.6 times and the rheumatologist 3.6 times. 78.6% had taken non-steroidal anti-inflammatory drug ever, 48.8% biological disease-modifying antirheumatic drugs and 43.6% conventional synthetic disease-modifying antirheumatic drugs. Patients's greatest fear was disease progression (55.9%), while the greatest hope was to be able to relieve pain (54.2%).
CONCLUSIONS
IMAS shows the global profile of patients with axSpA, highlighting unmet needs, lengthy delays in diagnosis and high burden of disease in patients with axSpA worldwide. This global information will enable more detailed investigations to obtain evidence on the critical issues that matter to patients around the world to improve their care and quality of life.
Topics: Humans; Male; Female; Adult; Cross-Sectional Studies; Middle Aged; Axial Spondyloarthritis; Quality of Life; Surveys and Questionnaires; Cost of Illness; Global Health; Severity of Illness Index
PubMed: 38851236
DOI: 10.1136/rmdopen-2023-003504 -
Rheumatology International Jun 2024This study analyzed the status of medical information acquisition through social media (SM) and its impact on healthcare utilization among patients with rheumatic...
This study analyzed the status of medical information acquisition through social media (SM) and its impact on healthcare utilization among patients with rheumatic diseases (RDs) who visited the rheumatology department of a tertiary hospital. We consecutively evaluated 102 patients with RDs in this single-center cross-sectional survey. Using a face-to-face survey, patients were asked about the sources they used to acquire medical information, factors influencing their visits to tertiary hospitals, and the potential impact of acquiring medical information on RDs through SM. SM refers to YouTube, Facebook, Instagram, Kakao Channel, Naver Band, and X. The mean age was 42.3 years and 39% were female. The most common disease was ankylosing spondylitis (45.1%), followed by rheumatoid arthritis (20.6%). The most frequent method for acquiring medical information regarding RDs, except for rheumatologists, was internet portal sites (47.8%), followed by SM (40.2%). The most important factor influencing the decision to visit a tertiary hospital was medical doctors (51%); only 1% of the patients responded that SM was the most crucial factor in determining their visit. Most patients (77.5%) responded that acquiring medical information through SM would help them manage their diseases. Our data revealed that a substantial proportion of patients with RDs obtained medical information through SM. However, the impact of SM on visiting a tertiary hospital was minimal, suggesting that SM has become a mainstream source of medical information, yet the reliability of SM remains relatively low. Rheumatology societies should establish SM platforms capable of providing high-quality medical information.
PubMed: 38850324
DOI: 10.1007/s00296-024-05634-0 -
Therapeutic Advances in Musculoskeletal... 2024Radiographic axial spondyloarthritis (r-axSpA), formerly known as ankylosing spondylitis (AS), is a chronic, inflammatory rheumatic disease associated with symptoms such...
BACKGROUND
Radiographic axial spondyloarthritis (r-axSpA), formerly known as ankylosing spondylitis (AS), is a chronic, inflammatory rheumatic disease associated with symptoms such as inflammatory back pain, morning stiffness, and arthritis. First-line recommendations for patients with AS include treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for reducing pain and stiffness.
OBJECTIVES
The objective of our study is to evaluate the efficacy and short-term NSAID-sparing effect of secukinumab in patients with AS currently treated with NSAIDs.
DESIGN
We assessed the clinical Assessment of SpondyloArthritis International Society (ASAS20) response to secukinumab and evaluated the extent to which the use of concomitant NSAID can be reduced between weeks 4 and 12 in r-axSpA patients treated with secukinumab 150 mg compared with placebo.
METHODS
ASTRUM was a prospective 24-week randomized controlled trial of adult patients with active r-axSpA [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ⩾4] who had a documented inadequate response to ⩾2 NSAIDs. Patients were randomized (1:1:1) to initiate treatment with subcutaneous secukinumab 150 mg from either week 0 (group 1), week 4 (group 2), or week 16 (group 3). From week 4 onward, tapering of NSAIDs was allowed in all groups.
RESULTS
This study included 211 patients ( = 71, 70, and 70 in groups 1, 2, and 3, respectively). ASAS20 response at week 12 for pooled groups 1 and 2 group 3 was 51.1% 44.3% ( = 0.35). A higher proportion of patients in groups 1 and 2 achieved ASAS40 and BASDAI50 and showed improvements in other secondary clinical outcomes as compared to group 3 at week 16. More patients in groups 1 and 2 group 3 stopped their NSAID intake from baseline through week 16.
CONCLUSION
Treatment with secukinumab improved clinical outcomes and showed a short-term NSAID-sparing effect in patients with r-axSpA, even though the primary endpoint was not met.
TRIAL REGISTRATION
ClinicalTrials.gov; NCT02763046, EudraCT 2015-004575-74.
PubMed: 38846755
DOI: 10.1177/1759720X241255486