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Therapeutic Advances in Respiratory... 2022Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their... (Review)
Review
Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their inflammatory component. However, there is a relative paucity of guidance on the management of this heterogeneous group of diseases. In ILDs other than IPF, immunosuppression is the cornerstone of therapy, with varying levels of evidence for different immunomodulatory agents and for each specific ILD. Classification of ILDs is important for guiding treatment decisions. Immunomodulatory agents mainly include corticosteroids, mycophenolate mofetil (MMF), azathioprine, methotrexate, cyclophosphamide and rituximab. In this review, the available evidence for single agents in the most common ILDs is first discussed. We then reviewed practical therapeutic approaches in connective tissue disease-related ILD and interstitial pneumonia with autoimmune features, scleroderma-related ILD, vasculitis and dermatomyositis with hypoxemic respiratory failure, idiopathic non-specific interstitial pneumonia, hypersensitivity pneumonitis sarcoidosis, fibrosing organizing pneumonia and eosinophilic pneumonia. The treatment of acute exacerbations of ILD is also discussed. Therapy augmentation in ILD is dictated by the recognition of progression of disease. Criteria for the evaluation of progression of disease are then discussed. Finally, specific protocol and measures to increase patients' safety are reviewed as well, including general monitoring and serologic surveillance, prophylaxis, patients' education, genetic testing for azathioprine, MMF serum levels and cyclophosphamide administration protocols. Immunomodulatory therapies are largely successful in the management of ILDs and can be safely managed with the application of specific protocols, precautions and monitoring.
Topics: Azathioprine; Cyclophosphamide; Disease Progression; Humans; Idiopathic Pulmonary Fibrosis; Immunomodulation; Lung Diseases, Interstitial
PubMed: 35938712
DOI: 10.1177/17534666221117002 -
Clinical and Molecular Hepatology Jan 2021Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence... (Review)
Review
Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence of AIH has been observed worldwide, along with a relative increase in the percentage of male patients. AIH is characterized and diagnosed based on serum biochemistry and liver histology: elevated aminotransferases and serum immunoglobulin G (IgG), the presence of serum anti-nuclear antibody or anti-smooth muscle antibody, and interface lympho-plasmacytic hepatitis. Clinical manifestations differ among disease subtypes with distinct time-frames, i.e., AIH with a chronic insidious onset, and acute-onset AIH (the diagnosis of which is often challenging due to the lack of typical serum findings). The absence of disease-specific biomarkers or histological findings may expand the disease phenotype into drug-induced AIH-like liver injury. Corticosteroids and azathioprine are recommended first-line treatments for AIH. The complete normalization of aminotransferases and serum IgG is an essential treatment response to ensure long-term overall survival. An incomplete response or intolerance to these drugs is considered an indication for second-line treatment, especially with mycophenolate mofetil. Life-long maintenance treatment is required for the majority of patients, but the few who achieve prolonged and stringent biochemical remission with lower alanine aminotransferase and IgG within the normal range may be able to discontinue the medications. In the future, the quality of life of AIH patients should be managed by personalized medicine, including the appropriate selection and dosing of first-line therapy and perhaps alternating with potential therapeutics, and the prediction of the success of treatment withdrawal.
Topics: Autoantibodies; Azathioprine; Hepatitis, Autoimmune; Humans; Mycophenolic Acid; Quality of Life
PubMed: 33291862
DOI: 10.3350/cmh.2020.0189 -
Postgraduate Medicine Jan 2023Takayasu's arteritis is a rare, chronic, large vessel vasculitis which affects the aorta and its large branches. Early diagnosis is important to prevent serious end... (Review)
Review
Takayasu's arteritis is a rare, chronic, large vessel vasculitis which affects the aorta and its large branches. Early diagnosis is important to prevent serious end organ damage, including to stroke and ischemic heart disease. Studies have demonstrated treatment response with methotrexate, azathioprine, and tumor necrosis factor (TNF) inhibitors. This article aims to describe to the reader key features of Takayasu's arteritis and highlights updated evidence in the diagnosis and management of these patients. We also review the 2021 ACR guidelines for Takayasu's arteritis and correlate them to the updated evidence discussed throughout the review. An extensive literature search was conducted via PUBMED, including the words 'Takayasu's diagnostic criteria,' 'Takayasu's treatment,' 'Takayasu's diagnosis,' 'Takayasu's imaging', and 'Takayasu's diagnostic criteria.' Search was filtered to include clinical trials, randomized controlled trials, systematic reviews, and meta-analyses. Articles in the English language or with English translation and published by the date of 20 December 2021 were included.
Topics: Humans; Takayasu Arteritis; Azathioprine
PubMed: 36588528
DOI: 10.1080/00325481.2022.2159723 -
The New England Journal of Medicine Nov 2014The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides.... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides. However, even when patients receive maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission.
METHODS
Patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. The primary end point at month 28 was the rate of major relapse (the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both).
RESULTS
The 115 enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) received azathioprine (58 patients) or rituximab (57 patients). At month 28, major relapse had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were similar in the two groups. Twenty-five patients in each group (P=0.92) had severe adverse events; there were 44 events in the azathioprine group and 45 in the rituximab group. Eight patients in the azathioprine group and 11 in the rituximab group had severe infections, and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group. Two patients in the azathioprine group died (1 from sepsis and 1 from pancreatic cancer).
CONCLUSIONS
More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).
Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Female; Humans; Immunologic Factors; Immunosuppressive Agents; Infections; Kaplan-Meier Estimate; Maintenance Chemotherapy; Male; Middle Aged; Neoplasms; Rituximab; Secondary Prevention
PubMed: 25372085
DOI: 10.1056/NEJMoa1404231 -
Nature Reviews. Rheumatology Mar 2020The introduction of biologic DMARDs into rheumatology has resulted in a substantial reduction of the burden of many rheumatic diseases. In the slipstream of the success... (Review)
Review
The introduction of biologic DMARDs into rheumatology has resulted in a substantial reduction of the burden of many rheumatic diseases. In the slipstream of the success achieved with these biologic DMARDs, some conventional immunosuppressive drugs have also found use in new indications. Notably, mycophenolate mofetil, azathioprine and tacrolimus have made their way from solid organ transplantation drugs to become useful assets in rheumatology practice. Mycophenolate mofetil and azathioprine inhibit the purine pathway and subsequently diminish cell proliferation. Both drugs have a pivotal role in the treatment of various rheumatic diseases, including lupus nephritis. Tacrolimus inhibits lymphocyte activation by inhibiting the calcineurin pathway. Mycophenolate mofetil and tacrolimus are, among other indications, increasingly being recognized as useful drugs in the treatment of interstitial lung disease in systemic rheumatic diseases and skin fibrosis in systemic sclerosis. A broad array of trials with mycophenolate mofetil, azathioprine and/or tacrolimus are ongoing within the field of rheumatology that might provide further novel avenues for the use of these drugs. In this Review, we discuss the historical perspective, pharmacodynamics, clinical indications and novel avenues for mycophenolate mofetil, azathioprine and tacrolimus in rheumatology.
Topics: Antirheumatic Agents; Azathioprine; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Mycophenolic Acid; Rheumatic Diseases; Rheumatology; Tacrolimus
PubMed: 32055040
DOI: 10.1038/s41584-020-0374-8 -
Hepatology (Baltimore, Md.) Dec 2022Autoimmune hepatitis (AIH) is a rare disease of unclear etiology characterized by loss of self-tolerance that can lead to liver injury, cirrhosis, and acute liver... (Review)
Review
Autoimmune hepatitis (AIH) is a rare disease of unclear etiology characterized by loss of self-tolerance that can lead to liver injury, cirrhosis, and acute liver failure. First-line treatment consists of systemic corticosteroids, or budesonide, and azathioprine, to which most patients are initially responsive, although predictors of response are lacking. Relapses are very common, correlate with histological activity despite normal serum transaminases, and increase hepatic fibrosis. Furthermore, current regimens lead to adverse effects and reduced quality of life, whereas medication titration is imprecise. Biomarkers that can predict the clinical course of disease, identify patients at elevated risk for relapse, and improve monitoring and medication dosing beyond current practice would have high clinical value. Herein, we review novel candidate biomarkers in adult and pediatric AIH based on prespecified criteria, including gene expression profiles, proteins, metabolites, and immune cell phenotypes in different stages of AIH. We also discuss biomarkers relevant to AIH from other immune diseases. We conclude with proposed future directions in which biomarker implementation into clinical practice could lead to advances in personalized therapeutic management of AIH.
Topics: Humans; Hepatitis, Autoimmune; Quality of Life; Azathioprine; Biomarkers; Liver Cirrhosis; Immunosuppressive Agents
PubMed: 35611859
DOI: 10.1002/hep.32591 -
Arthritis & Rheumatology (Hoboken, N.J.) Nov 2023We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE).
OBJECTIVE
We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE).
METHODS
Using observational data from a US multicenter electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011 and 2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab versus each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury.
RESULTS
Among 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison. The mean age of the cohort was 45 years, and 94% were women. Compared with azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HR 0.82; 95% confidence interval [CI] 0.72-0.92 and HR 0.69; 95% CI 0.61-0.78) and hospitalization for infection (HR 0.73; 95% CI 0.57-0.94 and HR 0.56 95% CI 0.43-0.71). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86; 95% CI 0.76-0.97). There were no differences in traumatic injury risks across treatment groups.
CONCLUSION
Belimumab was associated with lower risks of serious infection than with oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment.
Topics: Humans; Female; Middle Aged; Male; Immunosuppressive Agents; Azathioprine; Methotrexate; Lupus Erythematosus, Systemic; Treatment Outcome
PubMed: 37262382
DOI: 10.1002/art.42620 -
Practical Neurology Feb 2020Neurologists are very familiar with using corticosteroids and are aware of their considerable risk of adverse effects with prolonged use. Thus, we frequently consider... (Review)
Review
Neurologists are very familiar with using corticosteroids and are aware of their considerable risk of adverse effects with prolonged use. Thus, we frequently consider alternative immunosuppression or corticosteroid sparing agents. However, unlike other specialties, such as rheumatology, there are few indications for corticosteroid-sparing agents in neurology and so our experience is less extensive; even these indications may reduce further as more disease-modifying treatments become available for neurological conditions. Azathioprine is perhaps the most commonly used corticosteroid-sparing agent in neurology. This review aims to remind neurologists of important aspects of azathioprine prescribing, focussing on enhancing patient safety and clinician confidence in its prescribing.
Topics: Azathioprine; Humans; Immunosuppressive Agents; Methyltransferases; Nervous System Diseases; Neurologists
PubMed: 31444234
DOI: 10.1136/practneurol-2018-002161 -
The European Respiratory Journal Nov 2023Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF)....
BACKGROUND
Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).
METHODS
A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.
RESULTS
The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26-10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74-13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL ≥10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery p=0.013; replication p=0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD.
CONCLUSION
Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression.
Topics: Humans; Azathioprine; Retrospective Studies; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis; Immunosuppressive Agents; Connective Tissue Diseases; Immunosuppression Therapy; Telomere
PubMed: 37591536
DOI: 10.1183/13993003.00441-2023 -
Ugeskrift For Laeger Nov 2022In this case report, a 57-year-old male presented with circulatory collapse, systemic inflammation and acute generalized exanthematous pustulosis a week after initiation...
In this case report, a 57-year-old male presented with circulatory collapse, systemic inflammation and acute generalized exanthematous pustulosis a week after initiation of azathioprine treatment (AZA). He was presumed to have sepsis, AZA was paused, and he was treated with antibiotics. Re-initiation of AZA post recovery caused a relapse of symptoms and anuric renal failure within three hours. He was diagnosed with the rare and potentially fatal azathioprine hypersensitivity syndrome (AHS), a type-IV hypersensitivity reaction. A skin biopsy can support diagnosis, and upon suspicion of AHS, AZA should be stopped, and re-exposure avoided.
Topics: Male; Humans; Middle Aged; Azathioprine; Syndrome; Hypersensitivity, Delayed; Anti-Bacterial Agents; Biopsy
PubMed: 36426815
DOI: No ID Found