-
Doklady. Biochemistry and Biophysics Jun 2024Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the...
Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57-secukinumab (SEC), 22-netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065-0.107), during IL17-i therapy- 9.2 per 100 pt-years (95% CI 0.06-0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079-0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028-0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019-022), p = 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18-0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18-0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group.
PubMed: 38861150
DOI: 10.1134/S1607672924700868 -
Doklady. Biochemistry and Biophysics Jun 2024The objective of the study was to analyze whether axial psoriatic arthritis (axPsA) patients meet classification criteria for axial spondyloarthritis (axSpA) and...
The objective of the study was to analyze whether axial psoriatic arthritis (axPsA) patients meet classification criteria for axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS). A total of 104 patients (66 men and 38 women) with PsA according to CASPAR criteria were examined, all patients had back pain. Patients were evaluated for presence of inflammatory back pain (IBP) by ASAS criteria. Back pain not meeting the ASAS criteria was taken to be chronic back pain (chrBP). Patients underwent hands, feet and pelvis, cervical spine and lumbar spine X-rays. Erosions, osteolysis, and juxta-articular new bone formation were evaluated. Definite radiographic sacroiliitis (d-rSI) was defined as bilateral grade ≥ 2 or unilateral grade ≥ 3. Nineteen patients without d-rSI underwent sacroiliac joints MRI. Ninety-three patients underwent HLA B27 examination. The number of patients who met the criteria for axSpA (ASAS) and the modified New York (mNY) criteria for AS was determined. IBP was identified in 67 (64.4%) patients; chrBP, in 37 (35.6%) patients; 31 (29.8%) patient were of older age (over 40) at the onset of IBP/chrBP; 57 (58.8%) patients had d-rSI; 6 (31.6%) patients had MRI-SI; syndesmophytes were detected in 57 (58.8%) cases. Among 40 patients without d-rSI, 19 (47.5%) had syndesmophytes. In 38/97 (39.2%) patients d-rSI was detected along with syndesmophytes, while 19/97 (19.6%) patients had isolated d-rSI without spondylitis, and 19/97 (19.6%) patients had isolated syndesmophytes without d-rSI. HLA B27 was present in 28 (30.1%) cases. 51 (55.4%) patients met criteria for axSpA. Forty-one (44.6%) patients did not meet criteria for axSpA; however, 27 (65.9%) of them had syndesmophytes. Forty-eight (48.5%) PsA patients met mNY criteria for AS. Among these patients, a set of specific features was revealed: 18 (37.5%) had no IBP, 18 (37.5%) were of older age (over 40) at the onset of IBP/chrBP, 34 (70.8%) had dactylitis, 38 (79.2%) had erosive polyarthritis, 23 (48.8%) had juxta-articular new bone formation, 14 (30.2%) had osteolysis, 23 (48.9%) had "chunky" non-marginal syndesmophytes, and 40 (82.6%) had nail psoriasis; 28 (66.6%) patients were HLA-B27 negative. Forty-five percent of axPsA patients do not meet criteria for axSpA. Characteristic features have been identified to differentiate axPsA from AS.
PubMed: 38861144
DOI: 10.1134/S160767292470087X -
Radiology Jun 2024Whereas previous projects attempted to standardize imaging in patients with axial spondyloarthritis (axSpA), few studies have been published about the need for specific... (Review)
Review
Whereas previous projects attempted to standardize imaging in patients with axial spondyloarthritis (axSpA), few studies have been published about the need for specific details regarding the image acquisition and lesions that may be less familiar to general radiologists. This work reports consensus recommendations developed by the Assessment of SpondyloArthritis International Society (ASAS) that aim to standardize the imaging reports in patients suspected of having or with known axSpA. A task force consisting of radiologists and rheumatologists from ASAS and one patient representative formulated two surveys that were completed by ASAS members. The results of these surveys led to the development of 10 recommendations that were endorsed by 73% (43 of 59) of ASAS members. The recommendations are targeted to the radiologist and include best practices for the inclusion of clinical information, technical details, image quality, and imaging findings in radiology reports. These recommendations also emphasize that imaging findings that indicate differential diagnoses and referral suggestions should be included in the concluding section of the radiology report. With these recommendations, ASAS aims to improve the diagnostic process and care for patients suspected of having or with known axSpA.
Topics: Humans; Sacroiliac Joint; Axial Spondyloarthritis; Societies, Medical; Spondylarthritis; Diagnosis, Differential; Magnetic Resonance Imaging
PubMed: 38860891
DOI: 10.1148/radiol.231786 -
Rheumatology and Therapy Jun 2024With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS),...
Comparative Efficacy of Advanced Therapies in the Treatment of Radiographic Axial Spondyloarthritis or Ankylosing Spondylitis as Evaluated by the ASDAS Low Disease Activity Criteria.
INTRODUCTION
With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations.
METHODS
A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed.
RESULTS
Among the TNFi-naïve population, the estimated ASDAS LDA rate between week 12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies.
CONCLUSIONS
Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers.
PubMed: 38858318
DOI: 10.1007/s40744-024-00685-y -
The Journal of Dermatological Treatment Dec 2024The incidence of cutaneous paradoxical reactions associated with IL-17 inhibitors has gained attention in recent literature. Our report aims to investigate the... (Review)
Review
The incidence of cutaneous paradoxical reactions associated with IL-17 inhibitors has gained attention in recent literature. Our report aims to investigate the characteristics of one rare paradoxical reaction, presenting as Behcet's disease. We reported one case of Behcet's-like disease induced by secukinumab in a patient with psoriasis. This patient, a young woman with a long history of psoriasis, showed significant improvement in her psoriatic condition after receiving four doses of secukinumab. Unexpectedly, she developed symptoms such as high fever, painful oral and genital ulcers, facial maculopapules, and erythema nodosum-like lesions on her lower limbs. Despite neutrophilia, there was no evidence of infection found in her laboratory tests. Histological analysis of a skin biopsy highlighted subcutaneous panniculitis and a mixed inflammatory cell infiltrate in the dermis. The patient was consequently diagnosed with secukinumab-induced Behcet's-like disease. Additionally, we have reviewed nine other documented cases of Behcet's-like disease triggered by IL-17 inhibitors. This group showed no significant gender preference, suffering from conditions such as psoriasis, ankylosing spondylitis, and hidradenitis suppurativa. Oral and genital ulcers were prevalent among the paradoxical reactions noted. Marked improvement was observed in all patients upon discontinuation of the IL-17 inhibitors. Our report serves to alert physicians to this uncommon but significant paradoxical effect that may arise with anti-IL-17 treatment.
Topics: Humans; Female; Antibodies, Monoclonal, Humanized; Behcet Syndrome; Psoriasis; Adult; Interleukin-17; Skin
PubMed: 38857894
DOI: 10.1080/09546634.2024.2347440 -
Rheumatology Advances in Practice 2024We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis.
OBJECTIVES
We aimed to study trabecular bone score (TBS) association with disease parameters and vertebral fractures (VFs) in patients with axial spondyloarthritis.
METHODS
Patients diagnosed with axial spondyloarthritis were included in this cross-sectional study. Dual-energy X-ray absorptiometry was used to measure BMD in the lumbar spine and TBS. Low TBS was defined as ≤1.31. The association between TBS and disease parameters including Ankylosing Spondylitis Disease Activity Score (ASDAS), BASDAI, BASFI and BASMI was studied using logistic regressions.
RESULTS
Our study included 56 patients, with a mean age of 38.9 ± 13.5 years and a mean disease duration of 12.7 ± 7.7 years. Patients with low TBS were significantly older and had higher waist circumference and body mass index. These patients also showed greater clinical activity, as evidenced by higher ASDAS-CRP, BASFI and BASMI scores ( < 0.05). In multivariate logistic regression, low TBS was associated with all disease parameters, except for BASMI: BASDAI (OR [95% CI] = 3.68 [1.48-9.19], = 0.005), ASDAS-CRP (OR [95% CI] = 2.92 [1.20-7.10], = 0.018), BASFI (OR [95% CI] = 1.04 [1.01-1.08], = 0.018), BASMI (OR [95% CI] = 1.36 [0.99-1.87], = 0.062). However, no association was observed between TBS and VFs.
CONCLUSION
TBS was associated with active spondyloarthritis, suggesting increased bone fragility in these patients. However, TBS failed to demonstrate an association with VFs.
PubMed: 38855629
DOI: 10.1093/rap/rkae071 -
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