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Alimentary Pharmacology & Therapeutics Jul 2024Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We... (Meta-Analysis)
Meta-Analysis Comparative Study Review
INTRODUCTION
Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA).
METHODS
We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509).
RESULTS
Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses.
CONCLUSIONS
We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.
Topics: Humans; Crohn Disease; Network Meta-Analysis; Biological Products; Treatment Outcome; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Infliximab; Gastrointestinal Agents; Remission Induction; Severity of Illness Index
PubMed: 38863153
DOI: 10.1111/apt.18110 -
Cureus May 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the...
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the central nervous system. The following case report showcases a thorough analysis of a 21-year-old female patient presenting with MOGAD, outlining her clinical presentation, diagnostic workup, treatment protocol, and long-term management outcomes. Through a multidisciplinary approach, we aim to augment the understanding of this complex neurological entity and steer optimal therapeutic interventions.
PubMed: 38854354
DOI: 10.7759/cureus.59840 -
Cureus May 2024Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study... (Review)
Review
Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.
PubMed: 38854256
DOI: 10.7759/cureus.60049 -
Cureus May 2024Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system disease presenting as optic neuritis, myelitis, and brainstem syndromes. It may be...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system disease presenting as optic neuritis, myelitis, and brainstem syndromes. It may be aquaporin-4 seropositive, anti-myelin oligodendrocyte glycoprotein (MOG) antibody seropositive, or double seronegative. Double-seronegative NMOSD can pose a diagnostic and therapeutic challenge. Treatment typically aims to decrease the incidence of relapse, for which high-dose intravenous methylprednisolone is the first-line agent. Non-steroid treatments include azathioprine, mycophenolate mofetil, and rituximab. This case describes a 45-year-old female presenting with left arm numbness and weakness for three months. She had been previously diagnosed with optic neuritis in 2013 but was lost to follow-up. Progression of weakness warranted admission to the neurology department. Diagnostic work and imaging were suggestive of neuromyelitis optica. Tests for aquaporin-4, anti-MOG, immunoglobulin G, and immunoglobulin M in the cerebrospinal fluid were all negative. Initial treatment comprised methylprednisolone; however, due to the progression of symptoms, she was given two cycles of rituximab. Rituximab targets the CD20 antigen in B cells and is thought to reduce the risk of relapse and the severity of NMOSD. The patient's Barthel index score, expanded disability status scale score, and motor examination improved after two cycles of rituximab.
PubMed: 38854188
DOI: 10.7759/cureus.60004 -
Cureus May 2024Introduction Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical and laboratory features. The incidence increases markedly in...
Introduction Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical and laboratory features. The incidence increases markedly in women. The reason for the predominance of the female gender is still under study. The ethnicity could influence the clinical and serological features of SLE. Material and methods This is a retrospective, descriptive, and longitudinal study. We studied 89 patients diagnosed with childhood-onset systemic lupus erythematosus (cSLE) in our center in 2000-2020 for men and 2010-2020 for women. We investigated disease manifestations, ranging from clinical symptoms to renal involvement, at the time of diagnosis and compared them by gender. Results We studied 89 patients, comprising 23 males and 66 females. The mean age for both groups was 12 years. Concerning clinical manifestations, serositis exhibited a higher prevalence among males, while hair loss was more prominent among females. In the paraclinical evaluation, noteworthy differences were observed regarding average hemoglobin levels and the prevalence of positive anti-DNA antibodies. Males demonstrated an average hemoglobin level of 11.47 g/dL, whereas females displayed 9.84 g/dL (p=0.017). The prevalence of anti-DNA antibodies exhibited marked elevation in males, at 88.9%, compared to females' 42.9% (p=0.024). On a contrary note, our male cohort displayed heightened prevalence in using hydroxychloroquine, cyclophosphamide, and mycophenolate. Similarly, renal involvement presented a higher prevalence in males (100% against 83.3%), albeit lacking statistical significance. Nevertheless, significant disparities emerged in the occurrence of granular casts, proteinuria, and the average glomerular filtration rate, with males experiencing greater impact in each instance. Finally, it is noteworthy that the application of mycophenolate and azathioprine was more frequently observed among patients with renal involvement. Conclusion cSLE patients in our inception cohort showed statistical significance in dermatological and vascular manifestations, serositis, granular casts, low kidney glomerular filtration, and high proteinuria, which are predominant in male patients. Immunological features were predominantly positive in ds-DNA antibodies for male patients. Separation by gender for future studies might identify a better treatment strategy.
PubMed: 38854180
DOI: 10.7759/cureus.59851 -
Transplantation Proceedings Jun 2024This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney...
Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies.
INTRODUCTION
This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy.
METHODS
A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events.
RESULTS
Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138).
CONCLUSION
Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.
PubMed: 38853029
DOI: 10.1016/j.transproceed.2024.05.014 -
Journal of the Formosan Medical... Jun 2024Liver dysfunction in systemic lupus erythematosus (SLE) is caused by disease activity or secondary conditions like coexistent autoimmune liver diseases. In Taiwan,...
Liver dysfunction in systemic lupus erythematosus (SLE) is caused by disease activity or secondary conditions like coexistent autoimmune liver diseases. In Taiwan, despite sporadically reported cases of SLE-autoimmune hepatitis (AIH) overlap disease, larger-scale monocentric investigations for such overlapping patients are not available. Retrospective analyses were performed in a hospitalized SLE cohort with 805 patients for identifying co-existent AIH from 2014 to 2023, focusing on distinct therapeutic modalities and differential diagnosis between SLE-AIH overlap and lupus hepatitis (LH). There were 5 cases (a 0.6% occurrence), all females aged 25-58 years (44 ± 13). Ages for the SLE diagnosis were 19-51 years (30 ± 13), while ages for the AIH diagnosis were 22-57 years (36 ± 14). Contradictory to interface hepatitis in SLE-AIH overlap, liver biopsy only demonstrated non-specific abnormalities in LH. Liver cirrhosis was identified in SLE-AIH overlap but not in LH. After corticosteroids/azathioprine therapy, there were normalized liver function in all LH. In 2 SLE-AIH overlap cases refractory to such therapy, one received B-cell depletion therapy (annual rituximab infusion, 375 mg/m weekly × 4) and another accepted living-donor liver transplantation from sibling due to advanced liver cirrhosis, leading to improved hepatic dysfunction in both.
PubMed: 38851914
DOI: 10.1016/j.jfma.2024.06.003 -
Annals of Medicine and Surgery (2012) Jun 2024The SARS-CoV-2 is the source of COVID-19, a respiratory disease. It typically manifests as restricted pulmonary symptoms, but autoimmune dysfunction might occasionally...
INTRODUCTION AND IMPORTANCE
The SARS-CoV-2 is the source of COVID-19, a respiratory disease. It typically manifests as restricted pulmonary symptoms, but autoimmune dysfunction might occasionally show up. A COVID-19 infection may cause a multi-system connective tissue disease known as systemic sclerosis (SSc). In patients who recovered from COVID-19, autoimmunity may have multiple underlying causes.
CASE PRESENTATION
The authors report the case of a 68-year-old female who, 1 month after contracting COVID-19, complained of dyspnoea and muscle exhaustion. The patient was treated for post-COVID syndrome. She developed symptoms of chronic dyspnoea, pale fingers, pursed lips, trouble chewing and swallowing, and muscle weakness after 7 weeks. A chest high-resolution computerised tomography (HRCT) scan suggested interstitial lung disease. Clinical characteristics and an autoantibody profile containing anti-Ro 52 and anti-centromere antibodies pointed towards SSc. She was treated with azathioprine and prednisolone at a reduced dosage, and she is now stable with monthly follow-ups.
CLINICAL DISCUSSION
COVID-19 might induce cytokine storms and immunological dysregulation, ultimately culminating in autoimmune manifestations. Several autoantibodies are observed in autoimmune illnesses in post-COVID-19 infection patients. Our situation is distinct because SSc following a COVID-19 infection is not commonly seen as an autoimmune illness.
CONCLUSION
The number of patients with rare autoimmune diseases, like SSc, following COVID-19 has been rising. Therefore, we should consider the possibility of autoimmune disease when looking into a patient who presents strangely or has developed new symptoms after COVID and should contact the patient's management immediately.
PubMed: 38846898
DOI: 10.1097/MS9.0000000000002032 -
Scientific Reports Jun 2024Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal...
Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal homeostasis. Altered PCs function is associated with diverse intestinal pathologies, including ileal Crohn's disease (CD). CD patients with ileal involvement have been previously demonstrated to display impairment in PCs and decreased levels of anti-microbial peptides. Although the immunosuppressive drug Azathioprine (AZA) is widely used in CD therapy, the impact of AZA on IEC differentiation remains largely elusive. In the present study, we hypothesized that the orally administered drug AZA also exerts its effect through modulation of the intestinal epithelium and specifically via modulation of PC function. AZA-treated CD patients exhibited an ileal upregulation of AMPs on both mRNA and protein levels compared to non-AZA treated patients. Upon in vitro AZA stimulation, intestinal epithelial cell line MODE-K exhibited heightened expression levels of PC marker in concert with diminished cell proliferation but boosted mitochondrial OXPHOS activity. Moreover, differentiation of IECs, including PCs differentiation, was boosted in AZA-treated murine small intestinal organoids and was associated with decreased D-glucose consumption and decreased growth rates. Of note, AZA treatment strongly decreased Lgr5 mRNA expression as well as Ki67 positive cells. Further, AZA restored dysregulated PCs associated with mitochondrial dysfunction. AZA-dependent inhibition of IEC proliferation is accompanied by boosted mitochondria function and IEC differentiation into PC.
Topics: Crohn Disease; Azathioprine; Paneth Cells; Humans; Cell Differentiation; Animals; Mice; Intestinal Mucosa; Female; Male; Ileum; Adult; Organoids; Epithelial Cells; Cell Proliferation; Middle Aged; Cell Line; Severity of Illness Index
PubMed: 38839896
DOI: 10.1038/s41598-024-63730-4 -
Rheumatology International Jul 2024Primary Sjögren's Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects...
BACKGROUND
Primary Sjögren's Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects females between 40 and 60 years old. So far, there is no treatment to cure SS; however, there is a list of medications that can ameliorate the symptoms. In addition, there has been no single test until now to detect pSS, but clinical and immunological investigations are applied as diagnostic tools. Therefore, this study aimed to explore the characteristics of pSS in Saudi patients based on the onset of the disease through laboratory findings and pharmaceutical management.
METHODOLOGY
This retrospective study examined diagnosed patients with pSS between 2018 and 2023 from the National Guard Hospital, Saudi Arabia. Data of pSS patients was categorized into two groups: early (under 40 years old) and late-onset (40 years old and above). Data on demographic information, mortality rate, and blood tests such as complete blood count (CBC), creatinine, erythrocyte sedimentation rate (ESR), and vitamin levels, in addition to prescribed medications, were collected from the patient's medical record. Chi-square and t-tests were mainly used, and statistical significance was determined at a P-value less than 0.05.
RESULTS
A total of 453 patients were included in the study, where the early-onset group comprised 136 and the late-onset group comprised 317 patients. The mean age of the early and late onset was 34.2 and 60.4, respectively. ESR was significantly higher in the early (46.3 mm/hr) and late-onset (49.8 mm/hr). The most common medication used by all pSS patients was hydroxychloroquine. However, artificial tears were mainly observed in the late-onset group. Other medications, such as pilocarpine, methotrexate, and azathioprine, were prescribed to pSS patients to a lesser extent.
CONCLUSION
This study suggests that the onset of pSS could occur even before the age of 40 among Saudi citizens. Notably, elevated ESR levels appeared to be a feature of pSS, which was consistent with other previous findings. The variability of some medications between early-onset and late-onset pSS may indicate disease progression. However, further investigations are required to confirm this observation.
Topics: Humans; Sjogren's Syndrome; Female; Adult; Retrospective Studies; Middle Aged; Male; Age of Onset; Saudi Arabia; Blood Sedimentation; Aged; Antirheumatic Agents
PubMed: 38839658
DOI: 10.1007/s00296-024-05626-0