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Journal of the European Academy of... Sep 2022The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four...
The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.
Topics: Adolescent; Azathioprine; Child; Cyclosporine; Dermatitis, Atopic; Eczema; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 35980214
DOI: 10.1111/jdv.18345 -
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 -
International Journal of Molecular... Oct 2022Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological,... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.
Topics: Humans; Autoimmune Pancreatitis; Rituximab; Azathioprine; Autoimmune Diseases; Immunoglobulin G; Immunologic Factors; Immunosuppressive Agents; Adrenal Cortex Hormones; Steroids; Recurrence; Biological Products
PubMed: 36293522
DOI: 10.3390/ijms232012667 -
Journal of Neuroinflammation Sep 2021Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse... (Review)
Review
Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. NMO spectrum disorder (NMOSD) has recently been defined and stratified based on AQP4-ab serology status. Most NMOSD patients experience severe relapses leading to permanent neurologic disability, making suppression of relapse frequency and severity, the primary objective in disease management. The most common treatments used for relapses are steroids and plasma exchange.Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19 B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.
Topics: Animals; Antibodies, Monoclonal, Humanized; Aquaporin 4; Astrocytes; Autoantibodies; Azathioprine; Clinical Trials, Phase III as Topic; Humans; Immunosuppressive Agents; Neuromyelitis Optica
PubMed: 34530847
DOI: 10.1186/s12974-021-02249-1 -
Gut and Liver Jul 2020Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease, characterized by the elevation of aminotransferases, presence of anti-nuclear antibody or anti-smooth... (Review)
Review
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease, characterized by the elevation of aminotransferases, presence of anti-nuclear antibody or anti-smooth muscle antibody, elevated immunoglobulin G (IgG), and interface hepatitis/plasma-lymphocytic inflammation based on histology. Recent epidemiological studies have indicated an increasing trend in the prevalence of AIH worldwide, especially in male patients; this trend may suggest the alteration of environmental triggers of disease onset over time. As no disease-specific biomarker or histological finding is currently available, AIH requires a clinical diagnosis, and a validated diagnostic scoring system with acceptable specificity and sensitivity has been proposed. Regarding treatment, corticosteroids and azathioprine are recommended, and in those who exhibit an incomplete response or those who are intolerant to these drugs, second-line therapy, such as mycophenolate mofetil, is considered. Overall, the long-term outcome is excellent in patients with complete biochemical responses, while life-long maintenance treatment may be required since the cessation of immunosuppressive agents frequently leads to the relapse of the disease. Acute-onset AIH does occur, and the diagnosis is very challenging due to the lack of serum autoantibodies or elevated IgG. The unmet needs include earlier diagnosis, intervention with disseminated clinical practice guidelines, and recognition and improvement of patients' health-related quality of life with the development of novel corticosteroid-free treatment regimens.
Topics: Autoantibodies; Azathioprine; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Quality of Life
PubMed: 32301319
DOI: 10.5009/gnl19261 -
Current Rheumatology Reports May 2021To assess current management of Behcet's disease (BD). Controversies on therapeutic approaches to different manifestations, whether conventional immunosuppressives (IS)... (Review)
Review
PURPOSE OF REVIEW
To assess current management of Behcet's disease (BD). Controversies on therapeutic approaches to different manifestations, whether conventional immunosuppressives (IS) or biologic agents, should be chosen, and options for refractory disease are discussed.
RECENT FINDINGS
Glucocorticoids are still the main agents for remission-induction and azathioprine the first-line conventional IS in maintenance phase to prevent relapses of major organ involvement. Apremilast is shown to be a safe and effective option approved by the FDA for oral ulcers. Large case series confirmed the efficacy and safety of TNFα inhibitors and Interferon-α. Promising results are observed with IL-1 inhibitors, ustekinumab, secukinumab, and tocilizumab for refractory BD. Although both conventional IS and biologic agents are effectively used to suppress inflammation in BD, there is still an unmet need for clear therapeutic strategies in the management for different manifestations. Further controlled studies with new biologic agents, anticoagulants and the benefit of concomitant IS usage with biologics are needed to optimize the management of BD.
Topics: Anticoagulants; Azathioprine; Behcet Syndrome; Glucocorticoids; Humans; Immunosuppressive Agents; Remission Induction
PubMed: 34014377
DOI: 10.1007/s11926-021-01011-z -
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 -
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 -
International Journal of Molecular... Apr 2022Neuromyelitis optica spectrum disorders (NMOSD) are rare neurologic autoimmune diseases that have a poor prognosis if left untreated. For many years, generic oral... (Review)
Review
Neuromyelitis optica spectrum disorders (NMOSD) are rare neurologic autoimmune diseases that have a poor prognosis if left untreated. For many years, generic oral immunosuppressants and repurposed monoclonal antibodies that target the interleukin-6 pathway or B cells were the mainstays of drug treatment. Recently, these drug treatments have been complemented by new biologics developed and approved specifically for NMOSD. In principle, all of these drugs are effective, but treatment recommendations that take this into account are still pending. Instead, the choice of a drug may depend on other criteria such as drug safety or tolerability. In this review, we summarise current knowledge on the adverse effects of azathioprine, mycophenolate mofetil, rituximab, tocilizumab, eculizumab, satralizumab, and inebilizumab in NMOSD. Infections, cytopenias, and infusion-related reactions are most common, but the data are as heterogeneous as the manifestations are diverse. Nevertheless, knowledge of safety issues may facilitate treatment choices for individual patients.
Topics: Azathioprine; Drug-Related Side Effects and Adverse Reactions; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neuromyelitis Optica; Rituximab
PubMed: 35456972
DOI: 10.3390/ijms23084154