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The Canadian Journal of Cardiology Aug 2023Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of... (Review)
Review
Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of these recurrences is not well understood, and most cases remain idiopathic. Recent advances in medical therapy, including the use of colchicine and anti-interleukin-1 agents like anakinra and rilonacept, have suggested an autoinflammatory rather than an autoimmune mechanism for recurrences with an inflammatory phenotype. As a result, a more personalized approach to treatment is now recommended. Patients with an inflammatory phenotype (fever and elevated C-reactive protein level) should receive colchicine and anti-interleukin-1 agents as first-line therapy, whereas those without systemic inflammation should receive low to moderate doses of corticosteroids (eg, prednisone 0.2-0.5 mg/kg/d as an initial dose) and consider azathioprine and intravenous human immunoglobulins in the case of corticosteroid failure. Tapering of corticosteroids should be slow after achieving clinical remission. In this article, we review the new developments in the management of recurrent pericarditis.
Topics: Humans; Pericarditis; Azathioprine; Adrenal Cortex Hormones; Colchicine; Immunoglobulins, Intravenous; Recurrence
PubMed: 37075863
DOI: 10.1016/j.cjca.2023.04.008 -
Actas Dermo-sifiliograficas Jun 2020Pemphigus vulgaris (PV) is an uncommon, serious disease that is treated with systemic corticosteroids and corticosteroid-sparing agents.
BACKGROUND
Pemphigus vulgaris (PV) is an uncommon, serious disease that is treated with systemic corticosteroids and corticosteroid-sparing agents.
OBJECTIVES
To describe and analyze the demographic and clinical characteristics of patients with PV.
MATERIAL AND METHODS
Retrospective cohort study of adults diagnosed with PV over a period of 12years.
RESULTS
PV presented with mucosal lesions in 20 of the 32 patients studied (63%); the most common site was the oral mucosa followed by the vulva. Mucosal involvement was more common in women (P=.03). Lesions were found at more than 1 mucosal site in patients whose disease began in the mucosa, independently of age or sex (P=.003). Disease onset before the age of 40years was associated with generalized skin lesions (P=.003), a need for corticosteroid-sparing therapy (P=.05), and refractory PV (P=.02). Azathioprine was the most widely prescribed corticosteroid-sparing agent (in 22 patients). Eight patients (25%) were dependent on corticosteroids and disease recurred in 26 (81%). Complete remission, with or without treatment, was achieved in 15 patients (47%). Patients remained disease-free for a median of 14months, and 2 patients died (6%).
CONCLUSION
Onset before the age of 40 years could be a sign of poor prognosis in patients with PV, as it was significantly associated with a higher risk of generalized skin involvement, a need for corticosteroid-sparing therapy, and refractory disease.
Topics: Adrenal Cortex Hormones; Adult; Azathioprine; Female; Humans; Pemphigus; Retrospective Studies; Skin Diseases
PubMed: 32466985
DOI: 10.1016/j.ad.2019.10.004 -
Obstetrics and Gynecology Apr 2024Pregnant patients are often on immunosuppressant medications, most commonly to manage transplantation or autoimmune disorders. Most immunosuppressant agents, including... (Review)
Review
Pregnant patients are often on immunosuppressant medications, most commonly to manage transplantation or autoimmune disorders. Most immunosuppressant agents, including tacrolimus, corticosteroids, azathioprine, and calcineurin inhibitors, are safe during pregnancy and lactation. However, mycophenolic acid is associated with higher risks of birth defects and should be avoided in pregnancy. Tacrolimus, the commonly used drug in transplantation medicine and autoimmune disorders, requires monitoring of serum levels for dose adjustment, particularly during pregnancy. Although no pregnancy-specific therapeutic range exists, the general target range is 5-15 ng/mL, and pregnant patients may require higher doses to achieve therapeutic levels. Adherence to prescribed immunosuppressive regimens is crucial to prevent graft rejection and autoimmune disorder flare-ups. This review aims to provide essential information about the use of immunosuppressant medications in pregnant individuals. With a rising number of pregnant patients undergoing organ transplantations or having autoimmune disorders, it is important to understand the implications of the use of these medications during pregnancy.
Topics: Pregnancy; Female; Humans; Tacrolimus; Immunosuppressive Agents; Organ Transplantation; Azathioprine; Autoimmune Diseases
PubMed: 38227938
DOI: 10.1097/AOG.0000000000005512 -
Xenobiotica; the Fate of Foreign... Jan 2020The thiopurine drugs azathioprine and mercaptopurine are effective in the treatment of disorders of immune regulation and acute lymphoblastic leukaemia. Although... (Review)
Review
The thiopurine drugs azathioprine and mercaptopurine are effective in the treatment of disorders of immune regulation and acute lymphoblastic leukaemia. Although developed in the 1950s, thiopurines remained relevant in the anti-tumour necrosis factor biologic era, finding widespread use as a co-immunomodulator. Step changes in the management of patients treated with thiopurines have reduced the incidence of severe, sometimes life-threatening toxicity. Testing for thiopurine methyltransferase (TPMT) deficiency directs a safe initial dose for therapy. The introduction of red cell thioguanine nucleotide (TGN) monitoring provides a basis for dose adjustment and the identification of patients with high levels of red cell methylmercaptopurine (MMP) and an increase in the MMP:TGN ratio. These patients are at risk for hepatotoxicity and where TGN levels are sub-therapeutic, non-response to therapy. Switching thiopurine hypermethylators to low-dose thiopurine and allopurinol combination therapy resolves hepatoxicity and increases sub-therapeutic TGN levels to regain clinical response. variants are a common cause of severe myelotoxicity in Asian populations where the frequency of TPMT deficiency is low. There is increasing evidence that testing for NUDT15 and TPMT deficiency in all populations prior to the start of thiopurine therapy is clinically useful and should be the first step in personalising thiopurine therapy.
Topics: Azathioprine; Drug Hypersensitivity; Erythrocytes; Female; Genotype; Humans; Male; Mercaptopurine; Methyltransferases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Purine-Pyrimidine Metabolism, Inborn Errors; Purines
PubMed: 31682552
DOI: 10.1080/00498254.2019.1688424 -
Journal of Clinical Rheumatology :... Sep 2020
Topics: Azathioprine; Humans; Melanoma; Nail Diseases
PubMed: 30946288
DOI: 10.1097/RHU.0000000000001031 -
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
Gastroenterology Clinics of North... Dec 2020This article reviews nonbiologic immunosuppressive agents in the induction and maintenance of remission of ulcerative colitis. Based on meta-analyses and North American... (Review)
Review
This article reviews nonbiologic immunosuppressive agents in the induction and maintenance of remission of ulcerative colitis. Based on meta-analyses and North American guidelines, azathioprine, mercaptopurine, and methotrexate monotherapy are not recommended for induction therapy. Thiopurines are recommended in combination with infliximab. Tofacitinib has been shown to be an effective induction agent. Cyclosporine or tacrolimus are calcineurin inhibitors that can be used as induction therapy. Thiopurine monotherapy is suggested or recommended as maintenance therapy for patients who have achieved steroid-induced remission. Methotrexate monotherapy is not recommended. Tofacitinib has been shown to be an effective maintenance agent in moderate to severe disease.
Topics: Azathioprine; Colitis, Ulcerative; Contraindications, Drug; Glucocorticoids; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Mercaptopurine; Meta-Analysis as Topic; Methotrexate; Piperidines; Pyrimidines; Remission Induction
PubMed: 33121692
DOI: 10.1016/j.gtc.2020.07.003 -
Praxis Apr 2022Subacute Flaccid Tetraparesis The patient presented herself with a subacute flaccid tetraparesis. After clinical examination, laboratory analysis, EMG, MRI and muscle...
Subacute Flaccid Tetraparesis The patient presented herself with a subacute flaccid tetraparesis. After clinical examination, laboratory analysis, EMG, MRI and muscle biopsy we diagnosed a statin-associated immune-mediated necrotizing myopathy. Neurorehabilitation and prednisolone therapy as well as immunomodulatory therapy with azathioprine did not result in remission. After two cycles of Privigen®, the patient was almost symptom-free and no longer restricted in everyday life; the CK fell to 400U/l.
Topics: Autoantibodies; Autoimmune Diseases; Azathioprine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases
PubMed: 35473326
DOI: 10.1024/1661-8157/a003828 -
Annals of the New York Academy of... Sep 2019Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell... (Review)
Review
Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.
Topics: Antibodies, Monoclonal; Azathioprine; Cholinesterase Inhibitors; Humans; Immunosuppressive Agents; Immunotherapy; Myasthenia Gravis; Pyridostigmine Bromide; Treatment Outcome
PubMed: 31393614
DOI: 10.1111/nyas.14195 -
The Lancet. Gastroenterology &... May 2024Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker... (Randomized Controlled Trial)
Randomized Controlled Trial
A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial.
BACKGROUND
Management strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing outcomes in patients randomised to either top-down (ie, early combined immunosuppression with infliximab and immunomodulator) or accelerated step-up (conventional) treatment strategies.
METHODS
PROFILE (PRedicting Outcomes For Crohn's disease using a moLecular biomarker) was a multicentre, open-label, biomarker-stratified, randomised controlled trial that enrolled adults with newly diagnosed active Crohn's disease (Harvey-Bradshaw Index ≥7, either elevated C-reactive protein or faecal calprotectin or both, and endoscopic evidence of active inflammation). Potential participants had blood drawn to be tested for a prognostic biomarker derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, patients were randomly assigned, via a secure online platform, to top-down or accelerated step-up treatment stratified by biomarker subgroup (IBDhi or IBDlo), endoscopic inflammation (mild, moderate, or severe), and extent (colonic or other). Blinding to biomarker status was maintained throughout the trial. The primary endpoint was sustained steroid-free and surgery-free remission to week 48. Remission was defined by a composite of symptoms and inflammatory markers at all visits. Flare required active symptoms (HBI ≥5) plus raised inflammatory markers (CRP >upper limit of normal or faecal calprotectin ≥200 μg/g, or both), while remission was the converse-ie, quiescent symptoms (HBI <5) or resolved inflammatory markers (both CRP ≤ the upper limit of normal and calprotectin <200 μg/g) or both. Analyses were done in the full analysis (intention-to-treat) population. The trial has completed and is registered (ISRCTN11808228).
FINDINGS
Between Dec 29, 2017, and Jan 5, 2022, 386 patients (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) were randomised: 193 to the top-down group and 193 to the accelerated step-up group. Median time from diagnosis to trial enrolment was 12 days (range 0-191). Primary outcome data were available for 379 participants (189 in the top-down group; 190 in the accelerated step-up group). There was no biomarker-treatment interaction effect (absolute difference 1 percentage points, 95% CI -15 to 15; p=0·944). Sustained steroid-free and surgery-free remission was significantly more frequent in the top-down group than in the accelerated step-up group (149 [79%] of 189 patients vs 29 [15%] of 190 patients, absolute difference 64 percentage points, 95% CI 57 to 72; p<0·0001). There were fewer adverse events (including disease flares) and serious adverse events in the top-down group than in the accelerated step-up group (adverse events: 168 vs 315; serious adverse events: 15 vs 42), with fewer complications requiring abdominal surgery (one vs ten) and no difference in serious infections (three vs eight).
INTERPRETATION
Top-down treatment with combination infliximab plus immunomodulator achieved substantially better outcomes at 1 year than accelerated step-up treatment. The biomarker did not show clinical utility. Top-down treatment should be considered standard of care for patients with newly diagnosed active Crohn's disease.
FUNDING
Wellcome and PredictImmune Ltd.
Topics: Adult; Humans; Male; Female; Crohn Disease; Infliximab; Azathioprine; Biomarkers; Immunologic Factors; Inflammation; Leukocyte L1 Antigen Complex
PubMed: 38402895
DOI: 10.1016/S2468-1253(24)00034-7