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Annals of Medicine and Surgery (2012) Nov 2023Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare co-occurrence with systemic sclerosis, in around 2.5-9% of patients. The clinical...
INTRODUCTION AND IMPORTANCE
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare co-occurrence with systemic sclerosis, in around 2.5-9% of patients. The clinical manifestations and prognosis of vasculitis in systemic sclerosis depend on organ involvement. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers get along with purpuric vasculitis in some cases reports. Reports had found that survival in those with pulmonary-renal syndrome is poor. However, high-dose corticosteroids and cyclophosphamide increase the survival percent in those patients.
CASE PRESENTATION
An 81-year-old female was admitted for newly diagnosed acute renal failure and highly elevated C-reactive protein levels. She was diagnosed with systemic sclerosis 8 years previously, with a 3-year history of interstitial lung disease, and a 2-year history of pulmonary hypertension. Treatment included home oxygen on demand, prednisone 5 mg/day, and azathioprine 75 mg daily. On physical examination, she had sclerodactyly, both extremities ulcers, severe livedo reticularis, and hyperpigmented papules on her hand and feet. Laboratory findings included a markedly positive MPO (p-ANCA), and anti-Scl-70. She was treated with pulse methylprednisolone without any improvement. After a day, she developed anuria and became comatose. Then, she developed cardiac arrest, leading to death.
CLINICAL DISCUSSION
The presence of ANCA in systemic sclerosis patients ranges from 2.5 to 9% of systemic sclerosis patients. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers. The treatment with high-dose corticosteroids and cyclophosphamide is benefit. Survival in those with pulmonary-renal syndrome is poor.
CONCLUSION
The presence of ANCA-associated vasculitis is rarely reported with scleroderma. It occurs most commonly in women with limited or Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia (CREST) variants of scleroderma, as well as those with overlap features. Severe manifestations including pulmonary-renal syndrome and death may occur.
PubMed: 37915665
DOI: 10.1097/MS9.0000000000001347 -
Medicine Sep 2023Currently, there is no comprehensive bibliometric study in the literature on Crohn's disease (CD). The aim of this study was to analyze articles published on CD using...
Currently, there is no comprehensive bibliometric study in the literature on Crohn's disease (CD). The aim of this study was to analyze articles published on CD using bibliometric and statistical methods. The aim was to identify current research trends, show global productivity, and determine important players such as countries, journals, institutions, and authors. A total of 16,216 articles published on CD between 1980 and 2022 were analyzed using various statistical and bibliometric methods. Bibliometric network visualization maps were used to perform trend topic analysis, citation analysis, and international collaboration analysis. Spearman's correlation coefficient was used for correlation analysis. The top 3 contributing countries to the literature were the United States of America (USA) (n = 4344, 26.7%), the United Kingdom (UK) (n = 2036, 12.5%) and Germany (n = 1334, 8.2%). The most active institutions were Udice French Research Universities (n = 696), Assistance Publique Hopitaux Paris (n = 570), and Institut National de la Sante et de la Recherche Medicale Inserm (n = 479). The most productive journals were Inflammatory Bowel Diseases (n = 1100), Journal of Crohn's & Colitis (n = 579), and Gut (n = 510). The most prolific author was Colombel JF. (n = 290). The most frequently researched topics from past to present included infliximab, ulcerative colitis, surgery, pediatrics, adalimumab, magnetic resonance imaging, inflammation, perianal CD/perianal fistula, azathioprine, magnetic resonance enterography, small bowel, stricture/strictureplasty, recurrence, therapy/treatment, ustekinumab, mucosal healing, biomarkers, fistula, quality of life, ultrasonography, epidemiology, capsule endoscopy, laparoscopic surgery/laparoscopy, endoscopy, disease activity, postoperative recurrence, and the Nucleotide Binding Oligomerization Domain Containing 2 gene. We have seen an exponential increase in worldwide publications on CD. In recent years, the major research topics related to CD have been ustekinumab, vedolizumab, fecal calprotectin, therapeutic drug monitoring, biologics, biomarkers, exclusive enteral nutrition, microbiome/microbiota, magnetic resonance enterography, anti-TNF, postoperative complications, and mucosal healing. We determined that countries with large economies, particularly the United States, United Kingdom, Germany, France, Canada, Italy, Japan and China, have taken the lead in research contributions to the development of CD literature.
Topics: Humans; Child; Crohn Disease; Ustekinumab; Quality of Life; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases
PubMed: 37657036
DOI: 10.1097/MD.0000000000034817 -
Multiple Sclerosis and Related Disorders Apr 2024Satralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder...
BACKGROUND
Satralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database.
METHODS
We used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study.
RESULTS
Of the 131 patients included in the overall population, most were female (90.8 %), aged 18-65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0-351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date.
CONCLUSION
These real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.
Topics: Female; Humans; Male; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Aquaporin 4; Chronic Disease; Glucocorticoids; Immunosuppressive Agents; Japan; Neuromyelitis Optica; Recurrence; Retrospective Studies
PubMed: 38401202
DOI: 10.1016/j.msard.2024.105502 -
Transplantation Sep 2023Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation...
BACKGROUND
Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation confers risks to the recipient, transplant, and fetus, including gestational hypertension, preeclampsia, gestational diabetes, transplant dysfunction, preterm labor, and low birthweight infants. Additionally, mycophenolic acid (MPA) products are teratogenic. Literature evidence regarding belatacept, a selective T-cell costimulation blocker, during pregnancy and while breastfeeding is extremely limited. When female transplant recipients on a belatacept-based regimen are desirous of pregnancy or at the time of conception, transplant providers manage the immunosuppression regimen in 1 of 2 ways: (1) switch both belatacept and MPA to a calcineurin inhibitor-based regimen with or without azathioprine, which is the more common practice but requires several modifications, having potential negative outcomes; or (2) only switch MPA to azathioprine while continuing belatacept.
METHODS
This case series includes 16 pregnancies in 12 recipients with exposure to belatacept throughout pregnancy and while breastfeeding. Patient information was obtained from several sources, including Transplant Pregnancy Registry International, providers at Emory University, and Columbia University, as well as literature review.
RESULTS
Pregnancy outcomes included 13 live births and 3 miscarriages. No birth defects or fetal deaths were reported in any of the live births. Seven infants were breastfed while their mothers continued belatacept. Outcomes appear comparable to those documented with the administration of calcineurin inhibitors.
CONCLUSIONS
This case series provides data supporting the continued administration of belatacept during pregnancy. Additional research will assist in developing better guidelines to counsel female transplant recipients on belatacept desiring to pursue pregnancy.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Abatacept; Transplant Recipients; Azathioprine; Kidney Transplantation; Graft Rejection; Immunosuppressive Agents; Calcineurin Inhibitors; Pregnancy Outcome; Mycophenolic Acid
PubMed: 37287109
DOI: 10.1097/TP.0000000000004634 -
BMC Pulmonary Medicine Nov 2023Tofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren's syndrome (pSS)-associated interstitial...
Tofacitinib in the treatment of primary Sjögren's syndrome-associated interstitial lung disease: study protocol for a prospective, randomized, controlled and open-label trial.
INTRODUCTION
Tofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD) through its anti-inflammatory and antifibrotic effects.
METHODS AND ANALYSIS
This is a single-center, prospective, randomized, open-label trial. The trial will compare a 52-week course of oral tofacitinib with traditional therapy cyclophosphamide (CYC) combined with azathioprine (AZA) in the treatment of pSS-ILD. A total of 120 patients will be randomly assigned into two treatment groups with a 1:1 ratio and followed for 52 weeks from the first dose. The primary endpoint of the study is the increase of forced vital capacity (FVC) at 52 weeks. Secondary endpoints include high-resolution computed tomography (HRCT), diffusion capacity for carbon monoxide of the lung (DLCO), the Mahler dyspnea index, the health-related quality of life (HARQoL) score, the cough symptom score, EULAR Sjögren's syndrome disease activity index (ESSDAI), and safety.
DISCUSSION
This study will be the first randomized controlled trial to investigate tofacitinib compared to the traditional regimen of CYC in combination with AZA in the treatment of pSS-ILD, which will provide data on efficacy and safety and further elucidate the role of the JAK-STAT signaling pathway in the development of pSS-ILD.
ETHICS AND DISSEMINATION
Before starting the experiment, the research proposal, informed consent (ICF) and relevant documents in accordance with the ethical principles of the Helsinki Declaration and the relevant requirements of the local GCP rules for ethical approval shall be submitted to the ethics committee of the hospital. The ethical approval of this study is reviewed by the Ethics Committee of Tongji Hospital and the ethical approval number is 2021-LCYJ-007. When the experiment is completed, the results will also be disseminated to patients and the public through publishing papers in international medical journals.
TRIAL REGISTRATION
The study was registered on the Chinese Clinical Trial Registry, www.chictr.org.cn ; ID ChiCTR2000031389.
Topics: Humans; Azathioprine; Cyclophosphamide; Lung Diseases, Interstitial; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Sjogren's Syndrome
PubMed: 38007449
DOI: 10.1186/s12890-023-02774-0 -
Indian Journal of Dermatology 2023Vitiligo is a common acquired depigmentory skin disorder supposed to be of autoimmune aetiology. Different immunosuppressants have been tried with varying success....
BACKGROUND
Vitiligo is a common acquired depigmentory skin disorder supposed to be of autoimmune aetiology. Different immunosuppressants have been tried with varying success. Azathioprine has been less studied in vitiligo.
AIMS AND OBJECTIVES
To study the efficacy of oral azathioprine and compare with systemic steroid in the treatment of vitiligo.
MATERIALS AND METHODS
It was an interventional study with multi-armed (three), parallel group, an open-label, randomized controlled trial with allocation ratio of 1:1:1. Patients of vitiligo aged between 18 and 60 years having more than 5% body surface involvement were included in the study. Patients were divided into three groups. Group A-patients received oral azathioprine 50 mg OD daily, group B-patients received combination of oral azathioprine 50 mg OD and PUVASOL and group C-patients received combination of betamethasone oral mini pulse (OMP) and PUVASOL. All the groups were treated for 1 year. Repigmentation was evaluated by vitiligo area severity index (VASI), and stabilization was evaluated by vitiligo disease activity (VIDA).
RESULTS
Group A, group B and group C showed 24.24%, 53.24% and 47.28% improvement in VASI score, respectively, at the end of 1 year. Group B and group C showed statistically significant superior repigmentation as compared to azathioprine monotherapy. Though azathioprine and betamethasone showed equivalent efficacy, azathioprine has a better safety profile. Side effects were minimal in azathioprine groups, whereas 50% patients developed various side effects in group C.
CONCLUSION
Azathioprine is safe and effective option in the treatment of vitiligo.
PubMed: 38371565
DOI: 10.4103/ijd.ijd_865_22 -
World Journal of Hepatology Feb 2024The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine (AZA)....
The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine (AZA). Budesonide has shown promise in inducing a complete biochemical response (CBR) with fewer adverse effects and is considered an optional first-line treatment, particularly for patients without cirrhosis; however, it is worth noting that the design of that study favored budesonide. A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered. Current guidelines recommend mycophenolate mofetil (MMF) for patients who are intolerant to AZA. It is important to mention that the evidence supporting this recommendation is weak, primarily consisting of case series. Nevertheless, MMF has demonstrated superiority to AZA in the context of renal transplant. Recent comparative studies have shown higher CBR rates, lower therapeutic failure rates, and reduced intolerance in the MMF group. These findings may influence future guidelines, potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis. Until recently, the only alternative to corticosteroids was lifelong maintenance treatment with AZA, which comes with notable risks, such as skin cancer and lymphoma. Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies, whether relying on histological criteria, strict biochemical criteria, or a combination of both. Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo. However, these interesting findings have yet to be replicated by other research groups. Additionally, second-line drugs, such as tacrolimus, rituximab, and infliximab, should be subjected to controlled trials for further evaluation.
PubMed: 38495280
DOI: 10.4254/wjh.v16.i2.135 -
JGH Open : An Open Access Journal of... Jun 2024Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on... (Review)
Review
BACKGROUND
Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians.
METHODS
Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment.
RESULTS
Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine ( = 32) and methotrexate ( = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each.
CONCLUSION
The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.
PubMed: 38903487
DOI: 10.1002/jgh3.13076 -
The Journal of Clinical Endocrinology... Sep 2023Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Graves orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up.
METHODS
Three-year follow-up of a subset of the CIRTED trial (N = 68), which randomized patients to receive high-dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy.
RESULTS
Data were available at 3 years from 68 of 126 randomized subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a binary clinical composite outcome measure (BCCOM), modified European Group on Graves' Orbitopathy score, or Ophthalmopathy Index.Clinical Activity Score (CAS), Ophthalmopathy Index, and Total Eye Score improved over 3 years (P < .001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24 of 64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery [odds ratio (OR) 16.8; 95% CI 2.95, 95.0; P = .001]. Higher baseline levels of CAS, Ophthalmopathy Index, and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery.
CONCLUSION
In this long-term follow-up from a clinical trial, 3-year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes.
Topics: Humans; Graves Ophthalmopathy; Azathioprine; Follow-Up Studies; Quality of Life; Inflammation; Treatment Outcome
PubMed: 36971324
DOI: 10.1210/clinem/dgad084 -
Pharmaceuticals (Basel, Switzerland) Feb 2024Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis... (Review)
Review
Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.
PubMed: 38399463
DOI: 10.3390/ph17020248