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Respiratory Research Mar 2022Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Infliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis.
METHODS
Sarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations.
RESULTS
33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1-100) in CNS, 91.7% (95% CI 61.5-99.8) in cutaneous, 78.6% (95% CI 49.2-95.3) in pulmonary and 71.5% (95% CI 29.0-96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%.
CONCLUSION
Infliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.
Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Resistance; Female; Follow-Up Studies; Global Health; Glucocorticoids; Humans; Incidence; Infliximab; Male; Middle Aged; Prednisone; Recurrence; Retrospective Studies; Sarcoidosis; Time Factors; Treatment Outcome; Tumor Necrosis Factor Inhibitors
PubMed: 35264154
DOI: 10.1186/s12931-022-01971-5 -
Allergy and Asthma Proceedings Nov 2019Idiopathic anaphylaxis (IA) is defined as anaphylaxis without any identifiable precipitating agent or event. The clinical manifestations of IA are the same as... (Review)
Review
Idiopathic anaphylaxis (IA) is defined as anaphylaxis without any identifiable precipitating agent or event. The clinical manifestations of IA are the same as allergen-associated (immunologic) anaphylaxis and include urticaria, angioedema, hypotension, tachycardia, wheezing, stridor, pruritus, nausea, vomiting, flushing, diarrhea, dysphagia, light-headedness, and loss of consciousness. Patients usually tend to have the same manifestations on repeated episodes. IA is a prednisone-responsive disease that is ultimately a diagnosis of exclusion. Approximately 40% of patients are atopic. Serum tryptase (or urine histamine or its metabolite) will be elevated acutely, but, if elevated in the absence of anaphylaxis, should suggest alternative diagnoses, including indolent systemic mastocytosis. A focused history, examination, and follow-up will dictate whether a patient's symptoms may be attributable to disorders that mimic anaphylaxis, such as indolent systemic mastocytosis, carcinoid syndrome, pheochromocytoma, hereditary angioedema or acquired C1 esterase inhibitor deficiency, or panic attacks. The presence of urticaria may help limit the differential diagnosis because urticaria does not usually accompany any of the above-mentioned disorders, except for indolent systemic mastocytosis. IA is classified according to the symptoms as well as the frequency of attacks. Patients who experience six or more episodes in a year, or two or more episodes in 2 months are classified as having IA-frequent (IA-F). Patients who experience fewer episodes are classified as having IA-infrequent (IA-I). This distinction is important because patients with IA-F will initially require prednisone as disease-modifying therapy, whereas most patients who with IA-I will not require prednisone. Patients with IA must carry and know when and how to self-administer epinephrine.
Topics: Anaphylaxis; Diagnosis, Differential; Epinephrine; Humans; Mastocytosis, Systemic; Prednisone
PubMed: 31690394
DOI: 10.2500/aap.2019.40.4271 -
BMJ (Clinical Research Ed.) Jul 2014
Topics: Adrenal Insufficiency; Circadian Rhythm; Delayed-Action Preparations; Glucocorticoids; Half-Life; Hormone Replacement Therapy; Humans; Hydrocortisone; Prednisone
PubMed: 25077828
DOI: 10.1136/bmj.g4843 -
The Cochrane Database of Systematic... Jul 2019Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened...
BACKGROUND
Morphea (morphoea) is an immune-mediated disease in which excess synthesis and deposition of collagen in the skin and underlying connective tissues results in hardened cutaneous areas. Morphea has different clinical features according to the subtype and stage of evolution of the disease. There is currently no consensus on optimal interventions for morphea.
OBJECTIVES
To assess the effects of treatments for people with any form of morphea.
SEARCH METHODS
We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, and five trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical, intralesional, or systemic treatments (isolated or combined) in anyone who has been clinically diagnosed by a medical practitioner with any form of morphea. Eligible controls were placebo, no intervention, any other treatment, or different doses or duration of a treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were global improvement of disease activity or damage assessed by a medical practitioner or by participants, and adverse effects. Secondary outcomes were improvement of disease activity and improvement of disease damage. We used GRADE to assess the quality of the evidence for each outcome.
MAIN RESULTS
We included 14 trials, with a total of 429 randomised participants, aged between 3 and 76 years. There were juvenile and adult participants; over half were female, and the majority had circumscribed morphea, followed by linear scleroderma. The settings of the studies (where described) included a dermatologic centre, a national laboratory centre, paediatric rheumatology and dermatology centres, and a university hospital or medical centre.The studies evaluated heterogenous therapies for different types of morphea, covering a wide range of comparisons. We were unable to conduct any meta-analyses. Seven studies investigated topical medications, two evaluated intralesional medications, and five investigated systemic medications. The study duration ranged from seven weeks to 15 months from baseline.We present here results for our primary outcomes for our four key comparisons. All of these results are based on low-quality evidence.The included studies were at high risk of performance, detection, attrition, and reporting bias.Global improvement of disease activity or damage after treatment may be higher with oral methotrexate (15 mg/m², maximum 20 mg, once a week, for 12 months or until disease flare) plus oral prednisone (1 mg/kg a day, maximum of 50 mg, in a single morning dose, for three months, and one month with gradually decreased dose until discontinuation) than with placebo plus oral prednisone in children and adolescents with active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed) (risk ratio (RR) 2.31, 95% confidence interval (CI) 1.20 to 4.45; number needed to treat for an additional beneficial outcome (NNTB) 3; 1 randomised controlled trial (RCT); 70 participants, all juvenile). This outcome was measured 12 months from the start of treatment or until flare of the disease. Data were not available separately for each morphea type. There may be little or no difference in the number of participants experiencing at least one adverse event with oral methotrexate (26/46) or placebo (11/24) (RR 1.23, 95% CI 0.75 to 2.04; 1 RCT; 70 participants assessed during the 12-month follow-up). Adverse events related to methotrexate included alopecia, nausea, headache, fatigue and hepatotoxicity, whilst adverse events related to prednisone (given in both groups) included weight gain (more than 5% of body weight) and striae rubrae.One three-armed RCT compared the following treatments: medium-dose (50 J/cm²) UVA-1; low-dose (20 J/cm²) UVA-1; and narrowband UVB phototherapy. There may be little or no difference between treatments in global improvement of disease activity or damage, as assessed through the modified skin score (where high values represent a worse outcome): medium-dose UVA-1 phototherapy versus low-dose UVA-1 group: MD 1.60, 95% CI -1.70 to 4.90 (44 participants); narrowband UVB phototherapy versus medium-dose UVA-1 group: MD -1.70, 95% CI -5.27 to 1.87 (35 participants); and narrowband UVB versus low-dose UVA-1 group: MD -0.10, 95% CI -2.49 to 2.29 (45 participants). This RCT included children and adults with active morphea (circumscribed morphea, linear scleroderma (with trunk/limb variant and head variant), generalised morphea, or mixed morphea), who received phototherapy five times a week, for eight weeks. Outcomes were measured at eight weeks from the start of treatment.Safety data, measured throughout treatment, from the same RCT (62 participants) showed that treatment with UVA-1 phototherapy may cause mild tanning compared to narrowband UVB: narrowband UVB versus medium-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.42; 35 participants; narrowband UVB versus low-dose UVA-1: RR 0.03, 95% CI 0.00 to 0.41; 45 participants. However, there may be no difference in the number of participants reporting mild tanning when comparing medium and low dose UVA-1 phototherapy (RR 1.00, 95% CI 0.91 to 1.10; 44 participants). Transient erythema was reported in three participants with narrowband UVB and no participants in the low- or medium-dose UVA-1 groups.
AUTHORS' CONCLUSIONS
Compared to placebo plus oral prednisone, oral methotrexate plus oral prednisone may improve disease activity or damage in juvenile active morphea (linear scleroderma, generalised morphea or mixed morphea: linear and circumscribed), but there may be a slightly increased chance of experiencing at least one adverse event.When medium-dose UVA-1 (50 J/cm²), low-dose UVA-1 (20 J/cm²), and narrowband UVB were compared against each other in treating children and adults with active morphea (circumscribed morphea, linear scleroderma, generalised morphea and mixed morphea), there may be little or no difference between these treatments on global improvement of disease activity or damage. UVA-1 phototherapy may cause more mild tanning than narrowband UVB, but there may be no difference between medium- and low-dose UVA-1 phototherapy. These results are based on low-quality evidence.Limitations of data and analyses include risk of bias and imprecision (small number of participants or events and wide confidence intervals). We encourage multicentre RCTs to increase sample size and evaluate, with validated tools, different treatment responses according to the subtypes of morphea and age groups.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Male; Methotrexate; Middle Aged; Phototherapy; Prednisone; Randomized Controlled Trials as Topic; Scleroderma, Localized; Young Adult
PubMed: 31309547
DOI: 10.1002/14651858.CD005027.pub5 -
MMW Fortschritte Der Medizin Apr 2021
Review
Topics: Adolescent; Child; Child Health; Cluster Headache; Female; Humans; Prednisone; Pregnancy
PubMed: 33783782
DOI: 10.1007/s15006-021-9772-3 -
BMJ Case Reports Jun 2018
Topics: Adult; Antipruritics; Female; Histamine H1 Antagonists; Humans; Hydroxyzine; Pemphigoid Gestationis; Prednisone; Pregnancy; Pruritus
PubMed: 29914905
DOI: 10.1136/bcr-2018-225242 -
Blood Feb 2022
Topics: Cyclophosphamide; Prednisone; Rituximab; Vincristine
PubMed: 35201332
DOI: 10.1182/blood.2021013620 -
Obstetrics and Gynecology Aug 2015
Topics: Anti-Inflammatory Agents; Female; Granulomatous Mastitis; Humans; Immunosuppressive Agents; Methotrexate; Prednisone
PubMed: 26241441
DOI: 10.1097/AOG.0000000000000986 -
BMJ Case Reports Sep 2017A 53-year-old black woman presented with a 3-day history of abdominal pain. Ultrasound of the abdomen showed a gall bladder packed with small stones. She gave a history...
A 53-year-old black woman presented with a 3-day history of abdominal pain. Ultrasound of the abdomen showed a gall bladder packed with small stones. She gave a history of abdominal surgery for a gynaecological condition. She had a cholecystectomy done, but her symptoms continued after cholecystectomy. She then had anendoscopic retrograde cholangiopancreatogram (ERCP) and sphincterotomy done, again her symptoms remained the same. A CT scan of the abdomen was done, and mesenteric panniculitis was suspected. A laparoscopic biopsy of the mesentery was performed, and it confirmed mesenteric panniculitis. She was started on a 2-week course of steroids to which she responded very well. Three months after the initial presentation, she was still asymptomatic.
Topics: Abdominal Pain; Diagnosis, Differential; Female; Glucocorticoids; Humans; Laparoscopy; Mesentery; Middle Aged; Panniculitis, Peritoneal; Prednisone; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 28870885
DOI: 10.1136/bcr-2017-220910 -
Joint Bone Spine Nov 201970 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven... (Review)
Review
70 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven capacities in symptom severity and disease activity reduction, in particular when combined with a disease-modifying anti-rheumatic drug, such as methotrexate. Nevertheless, glucocorticoid administration, in long-term especially, is also seen critically because of its potential adverse conditions. In order to achieve a reduction in treatment-related adverse events, modern therapy regimes should take into consideration patients' risk factors and therefore be individual. The Glucocorticoid Toxicity Index is a method to measure side effects of glucocorticoid therapy objectively and will be central in future studies comparing different therapy regimes. Such a new therapy regime is modified-release prednisone, which - thanks to a different time of liberation - seems to capable of reducing morning stiffness much more effectively than conventional prednisone, whilst showing similar properties in disease activity reduction and safety. Still, confirmation of these first data in further trials will be necessary. Eventually, other innovative concepts are liposomal glucocorticoids, dissociated agonists of glucocorticoid receptors and intramuscular application of glucocorticoids. Though these approaches appear to be promising, additional research will be required.
Topics: Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Glucocorticoids; Humans; Long-Term Care; Male; Prednisone; Risk Assessment; Severity of Illness Index
PubMed: 30528678
DOI: 10.1016/j.jbspin.2018.11.006