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Pharmacotherapy Mar 2017Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal... (Review)
Review
Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Because it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged. In this review, we describe the literature associated with immunotherapy used to treat IRP in an adult population as well as provide an overview of the safety and monitoring parameters for each agent. The most common immunotherapies used after patients have had multiple recurrences of IRP are anakinra, intravenous immunoglobulin (IVIG), and azathioprine. In most cases, these immunotherapies are adjunctive therapy, with the goal of tapering and discontinuing immunosuppressive corticosteroids. After reviewing the data, anakinra resulted in more patients discontinuing corticosteroids and prevented further recurrences of pericarditis. IVIG resulted in symptom resolution and no further recurrences in most of the patients. Azathioprine was associated with more than half of patients becoming recurrence free; however, many patients required a restart of corticosteroids due to recurrence. Clinicians should be aware of the adverse effects of immunotherapy, ranging from mild gastrointestinal events to risk of infection and serious blood dyscrasias that may require diligent monitoring. The use of immunotherapy for the treatment of adults with IRP should be restricted to patients who have multiple recurrences. Ideally, immunotherapy would be adjunctive to first-line combination therapy with ASA/NSAID plus colchicine, with the goal of tapering and discontinuing immunosuppressive corticosteroids. Furthermore, clinicians should consider cost, drug-drug and drug-disease interactions, and safety, as well as the quality of the retrospective evidence before considering any immunotherapy.
Topics: Adult; Azathioprine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Interleukin 1 Receptor Antagonist Protein; Pericarditis; Recurrence
PubMed: 28079270
DOI: 10.1002/phar.1897 -
Orbit (Amsterdam, Netherlands) Aug 2022Idiopathic sclerosing orbital inflammatory syndrome (ISOIS) is a rare, progressive and hard to control disease. There is a deep gap of evidence regarding application of...
PURPOSE
Idiopathic sclerosing orbital inflammatory syndrome (ISOIS) is a rare, progressive and hard to control disease. There is a deep gap of evidence regarding application of disease-modifying drugs (DMD) regimen as a potentially effective treatment for orbital inflammatory diseases. We aimed to report the results of using DMDs and discuss the concept of applying this modality of treatment in patients with ISOIS.
METHODS
This was a prospective interventional case series conducted in a tertiary university-based hospital. Biopsy proven patients with active ISOIS were included. Systematic criteria were developed to define and measure disease activity and monitor response to treatment. A DMD regimen including an anti-tumor necrosis factor alpha (anti-TNF alpha) agent plus azathioprine and low-dose corticosteroids were used. Comprehensive ophthalmic, orbital and systemic assessments were performed during each visit.
RESULTS
Five eligible patients with primary ISOIS were included. Mean age was 34.20 (SD = 13.33, range 19-53) years. Three had unilateral and two had bilateral involvement. Four had diffuse orbital involvement pattern and progressive worsening of visual functions, reduced extraocular motility and proptosis. In one patient the disease was localized to extraocular muscle and lacrimal gland. Disease activity was decreased and stabilized after DMDs regimen in all patients. Mean follow up was 32.80 (SD = 30.80, range: 12-86) months.
CONCLUSION
Biologic DMD (b-DMD) including anti-TNF alpha, corticosteroid and azathioprine were effective in decreasing disease activity and could change course of the disease. This study supports the concept of using b-DMD regimen in treatment of ISOIS.
Topics: Adult; Azathioprine; Humans; Middle Aged; Orbital Pseudotumor; Prospective Studies; Tumor Necrosis Factor Inhibitors; Young Adult
PubMed: 34030586
DOI: 10.1080/01676830.2021.1929338 -
Expert Review of Clinical Immunology May 2022
Topics: Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid
PubMed: 35306959
DOI: 10.1080/1744666X.2022.2056020 -
Ceska a Slovenska Oftalmologie :... 2017IgG-4 related disease (IgG4-RD) is a recently discovered systemic fibro-inflammatory disease which affects the ocular system. This pathology is not limited only to the...
IgG-4 related disease (IgG4-RD) is a recently discovered systemic fibro-inflammatory disease which affects the ocular system. This pathology is not limited only to the orbit, but may also frequently affect the anatomical structures of the eye, as well as other organs. Suspicion of IgG4-RD is based on careful clinical, radiological and immuno-histological examination with a finding of characteristic histopathological changes. Increased values of serum IgG4 need not necessarily be an unequivocal diagnostic criterion for the diagnosis of IgG4-RD. Only a careful histological and immunophenotyping examination together with a clinical finding provide a basis for distinguishing IgG4-RD from other inflammatory pathologies. Corticoids are applied in the treatment of this disease, but they do not exclude the possibility of relapses of clinical manifestations. Second choice pharmaceuticals are azathioprine, mycophenolate mofetil, and the effect of treating relapse of the disease with rituximab is significant.Key words: IgG4 related disease, eye, diagnosis, treatment.
Topics: Azathioprine; Eye Diseases; Humans; Immunoglobulin G; Mycophenolic Acid; Orbit
PubMed: 29394077
DOI: No ID Found -
Journal of Digestive Diseases Oct 2016To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC).
METHODS
A literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate).
RESULTS
Six studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0-85.0%) and 88.0% (95% CI 80.0-96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0-31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6-month response rate and ADR rate.
CONCLUSIONS
Low-dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions.
Topics: Azathioprine; Chronic Disease; Colitis, Ulcerative; Colonoscopy; Drug Administration Schedule; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Publication Bias; Treatment Outcome; Wound Healing
PubMed: 27450969
DOI: 10.1111/1751-2980.12386 -
Journal of Crohn's & Colitis Apr 2018Thiopurines, available as azathioprine, mercaptopurine, and thioguanine, are immunomodulating agents primarily used to maintain corticosteroid-free remission in patients... (Review)
Review
Thiopurines, available as azathioprine, mercaptopurine, and thioguanine, are immunomodulating agents primarily used to maintain corticosteroid-free remission in patients with inflammatory bowel disease. To provide a state-of-the-art overview of thiopurine treatment in inflammatory bowel disease, this clinical review critically summarises the available literature, as assessed by several experts in the field of thiopurine treatment and research in inflammatory bowel disease.
Topics: Azathioprine; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Mercaptopurine; Neoplasms; Risk Factors; Thioguanine
PubMed: 29293971
DOI: 10.1093/ecco-jcc/jjx181 -
Autoimmunity Reviews Sep 2020Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune... (Review)
Review
Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES.
Topics: Autoimmune Diseases; Azathioprine; Child; Female; Humans; Immunosuppressive Agents; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Retrospective Studies
PubMed: 32240856
DOI: 10.1016/j.autrev.2020.102525 -
Medicine Sep 2022To assess the efficacy and safety of rituximab (RTX) in the treatment of neuromyelitis optica spectrum diseases (NMOSDs), and give a guideline on clinical medication. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To assess the efficacy and safety of rituximab (RTX) in the treatment of neuromyelitis optica spectrum diseases (NMOSDs), and give a guideline on clinical medication.
METHODS
The databases of Pubmed, Embase, Cochrane Library, CNKI, and Wan fang were systematically searched by computer, and the search period was from the establishment of the databases until January 2022. To collect the trials of RTX in the treatment of NMOSDs, two researchers completed literature screening, quality assessment, and data extraction independently. Statistical analysis was performed using Review Manager 5.3 and Stata 15.1 software.
RESULTS
There were 37 studies in the meta-analysis, including 5 randomized controlled trials (RCTs) and 32 observational studies. Meta-analysis results revealed that NMOSDs patients treated with RTX significantly reduced the annualized relapse rate (ARR) (weighted mean difference [WMD] = 1.45, 95% confidence interval [CI]: 1.24-1.66, P < .01) and the Expanded disability status scale (EDSS) scores (WMD = 1.34, 95%CI: 1.25-1.44, P < .01). RTX is more effective than azathioprine (AZA) in the treatment of NMOSDs (ARR: WMD = -0.54, 95% CI: -0.75 to -0.33; EDSS: WMD = -0.65, 95% CI: -0.83 to -0.48; P < .0001).There was no difference in ARR and EDSS scores between anti-aquapor in-4-antibody seropositive NMOSD and seronegative NMOSD patients treated with RTX (ARR: WMD = -0.01, 95% CI: -0.25 to 0.24, P = .96 > 0.05; EDSS: WMD = 0, 95% CI: -0.30 to 0.31, P = .99 > 0.05). In this study, 681 patients were recorded safety data of RTX therapy, 23% (156 patients) had adverse events, and 0.7% (5 patients) of NMOSDs discontinued due to severe adverse reactions.
CONCLUSIONS
NMOSDs patients treated with RTX can significantly reduce the relapse frequency and EDSS scores, and also improve neurological dysfunction, besides the efficacy is better than azathioprine. RTX has a high incidence of adverse reactions, which are mild and with certain self limited, it should be cautious in clinical medication.
Topics: Antibodies; Azathioprine; Humans; Neuromyelitis Optica; Recurrence; Rituximab
PubMed: 36086713
DOI: 10.1097/MD.0000000000030347 -
Gut Oct 2023Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several... (Review)
Review
Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands. In this paper, we aim to visualise potential hurdles that hamper drug rediscovery in general, emphasise the global need for optimal use and development of potentially useful drugs, and provide an overview of the registration process for TG in the Netherlands. With this summary, we aim to guide drug rediscovery trajectories in the near future.
Topics: Humans; Thioguanine; Off-Label Use; Gastroenterology; Inflammatory Bowel Diseases; Netherlands; Azathioprine; Mercaptopurine; Immunosuppressive Agents
PubMed: 37380330
DOI: 10.1136/gutjnl-2023-329679 -
Digestive Diseases and Sciences May 2021Standard of care treatment for AIH includes prednisone monotherapy or dual therapy prednisone-azathioprine. However, many hepatologists alternatively use azathioprine... (Comparative Study)
Comparative Study
BACKGROUND
Standard of care treatment for AIH includes prednisone monotherapy or dual therapy prednisone-azathioprine. However, many hepatologists alternatively use azathioprine monotherapy to avoid side effects of long-term corticosteroids.
AIMS
To determine whether azathioprine monotherapy is comparable to dual prednisone-azathioprine for maintenance of remission in AIH.
METHODS
A retrospective chart review of 260 individuals with AIH from a single institution was performed; 45 individuals were included. Exclusion criteria included concomitant PBC or PSC, use of alternative treatment regimen, and/or failure to reach remission. Treatment regimen received was guided by clinician standard of practice, not patients' clinical factors. Initial remission was defined as normalization of serum ALT for at least two consecutive blood draws. Data were analyzed for 5 years post-remission, recording outcome and dose of prednisone and/or azathioprine.
RESULTS
83% of individuals were female, and average age was 65 years. Median dose of prednisone and azathioprine for the dual-therapy group was 5 mg and 100 mg, respectively, while median azathioprine dose for the monotherapy group was 75 mg. Considering overall outcome, 93% of all patients maintained remission. 80% of the dual-therapy group, and 95% of the azathioprine monotherapy group maintained remission. Using Chi-square analysis to compare the maintenance of remission between dual therapy and azathioprine monotherapy, a p value of 0.28 was calculated.
CONCLUSIONS
AASLD guidelines recommend dual prednisone-azathioprine as standard of care for maintenance of remission in AIH. Our results suggest that azathioprine monotherapy is equivalent to prednisone-azathioprine. Azathioprine monotherapy offers a significant advantage in mitigating risks of long-term corticosteroid therapy.
Topics: Aged; Aged, 80 and over; Azathioprine; Drug Therapy, Combination; Female; Glucocorticoids; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 32436124
DOI: 10.1007/s10620-020-06347-7