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The Medical Letter on Drugs and... Mar 2024
Topics: Humans; Colitis, Ulcerative; Antibodies, Monoclonal, Humanized
PubMed: 38466213
DOI: 10.58347/tml.2024.1698c -
International Immunopharmacology Oct 2023Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents.
OBJECTIVE
The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU.
METHODS
PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects.
RESULTS
This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples.
CONCLUSION
Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.
Topics: Humans; Immunosuppressive Agents; Cyclosporine; Methotrexate; Azathioprine; Network Meta-Analysis; Chronic Disease; Chronic Urticaria; Histamine H1 Antagonists; Urticaria; Histamine Antagonists; Drug-Related Side Effects and Adverse Reactions; Glycosides; Treatment Outcome; Omalizumab; Anti-Allergic Agents; Randomized Controlled Trials as Topic
PubMed: 37567010
DOI: 10.1016/j.intimp.2023.110577 -
Current Rheumatology Reports Oct 2023Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies. (Review)
Review
PURPOSE OF REVIEW
Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies.
RECENT FINDINGS
Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.
Topics: Humans; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Kidney; Risk Factors
PubMed: 37452914
DOI: 10.1007/s11926-023-01109-6 -
Clinical Rheumatology Sep 2023Idiopathic granulomatous mastitis (IGM) is a rarely seen chronic and benign disease of the breast. IGM usually emerges in women between 30 and 45 years of age and...
INTRODUCTION
Idiopathic granulomatous mastitis (IGM) is a rarely seen chronic and benign disease of the breast. IGM usually emerges in women between 30 and 45 years of age and within the first 5 years after lactation. There is no consensus on the treatment of the disease. Steroids, immunosuppressive agents such as methotrexate and azathioprine, antibiotics, and surgical and conservative treatments can be preferred. In the present study, it was aimed to demonstrate the treatment options and follow-up data of the patients with IGM and to investigate the effective factors on recurrence if developed in the follow-up period.
MATERIALS AND METHOD
The data of 120 patients diagnosed with idiopathic granulomatous mastitis were evaluated for this cross-sectional retrospective study. The demographic, clinical, treatment, and follow-up features of the patients were obtained from the file records.
RESULTS
The median age value of the 120 female patients included in the study was 35 (24-67) years. Of the patients, 45%, 79.2%, 49.2%, and 15% had a past history of surgical intervention, steroid use, methotrexate use, and azathioprine use, respectively. Recurrent lesion developed after the treatment in 57 (47.5%) patients. The recurrence rate was 66.1% in the patients who underwent surgical intervention in the initial treatment. There was a statistically significant difference between the patients with and without recurrence regarding the presence of abscess, the presence of recurrent abscess, and having surgical intervention as the initial treatment in the past history. The rate of having surgery was statistically significantly higher compared with the administration of steroid therapy alone and the combination of steroid and immunosuppressive therapy in the initial treatment of the patients who developed recurrence. The rate of having surgery together with the administration of steroid and immunosuppressive therapy was statistically significantly higher than the administration of steroid and immunosuppressive therapies.
DISCUSSION
Our study showed that surgical intervention and the presence of abscess increased recurrence in the treatment of IGM. Key Points • This study has shown that surgical intervention and the presence of abscess increase recurrence. • A multidisciplinary approach to the treatment of IGM and management of the disease by the rheumatologists may be critical.
Topics: Female; Humans; Adult; Middle Aged; Aged; Methotrexate; Granulomatous Mastitis; Retrospective Studies; Azathioprine; Abscess; Cross-Sectional Studies; Treatment Outcome; Steroids; Immunoglobulin M; Recurrence
PubMed: 37301771
DOI: 10.1007/s10067-023-06651-3 -
Journal of Clinical Medicine Oct 2023This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active... (Review)
Review
This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.
PubMed: 37959208
DOI: 10.3390/jcm12216742 -
Cell Reports Aug 2023Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human...
Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.
PubMed: 37531252
DOI: 10.1016/j.celrep.2023.112899 -
Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Journal of Oncology Pharmacy Practice :... Dec 2023Vincristine is a vesicant chemotherapeutic agent which may leak from the vessel at the infusion site to the perivascular tissue and cause extravasation. Extravasation, a...
INTRODUCTION
Vincristine is a vesicant chemotherapeutic agent which may leak from the vessel at the infusion site to the perivascular tissue and cause extravasation. Extravasation, a severe complication of chemotherapeutic drugs, can result in tissue necrosis that is considered an oncological emergency.
CASE REPORT
We aimed to report a case of a 29-year-old woman with ALL-B cell (Acute lymphoblastic leukemia) on maintenance chemotherapy regimen including vincristine, methotrexate, prednisolone, and 6-mercaptopurine (POMP). 48 h after administering intravenous vincristine, the patient experienced burning, pain and tenderness at the injection site (left hand - cubital cavity).
MANAGEMENT & OUTCOME
7 days after the onset of symptoms, the patient was hospitalized with a large brown lesion at the site. She was prescribed betamethasone cream, DSMO (Dimethyl sulfoxide) solution, and oral levofloxacin on his second day after admission. The lesion was completely improved 10 days after initiation of therapy and there were no serious problems.
DISCUSSION
Due to the ineffectiveness of antidote therapy for the management of delayed extravasation of vincristine and beneficial effect of our clinical approach, it could consider for the management of similar cases with delayed extravasation following vincristine administration.
Topics: Female; Humans; Adult; Vincristine; Antineoplastic Combined Chemotherapy Protocols; Methotrexate; Mercaptopurine; Prednisolone
PubMed: 37475540
DOI: 10.1177/10781552231187591 -
Biomedicine & Pharmacotherapy =... Dec 2023Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such as Crohn's disease and...
Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such as Crohn's disease and rheumatoid arthritis), and in patients receiving organ transplants. Thiopurine-S-methyltransferase (TPMT) is a cytoplasmic trans-methylase catalyzing the S-methylation of thiopurines. The active metabolites obtained from thiopurines are hydrolyzed into inactive forms by the Nudix hydrolase 15 (NUDT15). The TPMT*2 (defined by rs1800462), *3A (defined by rs1800460 and rs1142345), *3B (defined by rs1800460), *3C (defined by rs1142345), *6 (defined by rs75543815), and NUDT15 rs116855232 genetic variant have been associated, with the highest level of evidence, with the response to azathioprine, and, the approved drug label for azathioprine and main pharmacogenetic dosing guidelines recommend starting with reduced initial doses in TPMT intermediate metabolizer (IM) patients and considering an alternative treatment in TPMT poor metabolizer (PM) patients. This study aims to assess the clinical impact of azathioprine dose tailoring based on TPMT genotyping studying the azathioprine toxicity and efficacy, treatment starts, and dose adjustments during follow-up, comparing TPMT IM/PM and normal metabolizer (NM) patients. It also studied the association of NUDT15 rs116855232 with response to azathioprine in patients receiving a tailored treatment based on TPMT and characterized the TMPT and NUDT15 studied variants in our population. Results show that azathioprine dose reduction in TPMT IM patients (TPMT*1/*2, *1/*3A, or *1/*3C genotypes) is related to lower toxicity events compared to TPMT NM (TPMT *1/*1 genotype), and lower azathioprine dose adjustments during follow-up without showing differences in the efficacy. The results support the hypothesis of existing other genetic variants affecting azathioprine toxicity.
Topics: Humans; Azathioprine; Pharmacogenetics; Immunosuppressive Agents; Genotype; Crohn Disease; Methyltransferases; Pyrophosphatases
PubMed: 37857254
DOI: 10.1016/j.biopha.2023.115706