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BioDrugs : Clinical Immunotherapeutics,... Jan 2023Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.
Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase).
INTRODUCTION
Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited.
OBJECTIVE
The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases.
METHODS
We performed a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database from 1968 to June 1, 2021. Data were collected in June 2021. By using terms for different hierarchical levels of the Medical Dictionary for Regulatory Activities, we selected the following fetal or neonatal ADRs: stillbirth, premature birth, low birth weight, small for gestational age, and congenital malformations. The frequency of all identified ADRs for biologics of interest (adalimumab, infliximab, golimumab, certolizumab, etanercept, anakinra, canakinumab, tocilizumab, sarilumab, ustekinumab, guselkumab, secukinumab, ixekizumab, belimumab, abatacept, and rituximab) was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]. Reports with known concomitant use of teratogenic drugs were excluded from the main analysis. Other analyses included ROR stratifications by therapeutic indication in the periods 1968-2021 and 2001-2021, and an analysis after excluding reports with steroids.
RESULTS
In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50-14.73]), canakinumab (19.54 [12.82-29.79]), and abatacept (5.09 [2.77-9.33]), and for immune system disorders with canakinumab (347.88 [217.9-555.50]) and rituximab (9.27 [2.95-29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75-141.25]).
CONCLUSION
We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Rituximab; Abatacept; Biological Products; Interleukin 1 Receptor Antagonist Protein; Pharmacovigilance; Autoimmune Diseases; World Health Organization; Drug-Related Side Effects and Adverse Reactions; Adverse Drug Reaction Reporting Systems
PubMed: 36401769
DOI: 10.1007/s40259-022-00564-4 -
Revue Medicale de Liege Jul 2020This is the case report of a 57-year-old women with a 10-year long history of urticarial-like exanthema and monoclonal immunoglobulin M Kappa gammopathy, associated to...
This is the case report of a 57-year-old women with a 10-year long history of urticarial-like exanthema and monoclonal immunoglobulin M Kappa gammopathy, associated to arthralgia with pain of the lower limbs. A cutaneous biopsy and an inflammatory syndrome on laboratory testing helped to diagnose an urticarial vasculitis. A treatment with colchicine was set up but the response to therapy was not satisfactory. The diagnosis of Schnitzler syndrome was eventually suggested based on the combination of monoclonal gammopathy, urticarial and pain. A therapy with anakinra, an interleukin-1-receptor antagonist (IL-1), was started accordingly. The response was remarkable on skin rash, bone pain and laboratory testing including inflammatory syndrome.
Topics: Biopsy; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Middle Aged; Schnitzler Syndrome; Skin; Urticaria
PubMed: 32779911
DOI: No ID Found -
The Israel Medical Association Journal... 2016Behçet's disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an... (Review)
Review
Behçet's disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and intriguing new pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration, and organ response.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Autoimmunity; Behcet Syndrome; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Treatment Outcome
PubMed: 27228638
DOI: No ID Found -
Arthritis Research & Therapy Jul 2023The objective of this systematic review was to assess the effects of interleukin-1β (IL-1β) inhibitors on gout flares. (Review)
Review
OBJECTIVES
The objective of this systematic review was to assess the effects of interleukin-1β (IL-1β) inhibitors on gout flares.
METHODS
Studies published between 2011 and 2022 that evaluated the effects of IL-1β inhibitors in adult patients experiencing gout flares were eligible for inclusion. Outcomes including pain, frequency and intensity of gout flares, inflammation, and safety were assessed. Five electronic databases (Pubmed/Medline, Embase, Biosis/Ovid, Web of Science and Cochrane Library) were searched. Two independent reviewers performed study screening, data extraction and risk of bias assessments (Cochrane Risk of Bias Tool 2 for randomised controlled trials [RCTs] and Downs and Black for non-RCTs). Data are reported as a narrative synthesis.
RESULTS
Fourteen studies (10 RCTs) met the inclusion criteria, with canakinumab, anakinra, and rilonacept being the three included IL-1β inhibitors. A total of 4367 patients with a history of gout were included from the 14 studies (N = 3446, RCTs; N = 159, retrospective studies [with a history of gout]; N = 762, post hoc analysis [with a history of gout]). In the RCTs, canakinumab and rilonacept were reported to have a better response compared to an active comparator for resolving pain, while anakinra appeared to be not inferior to an active comparator for resolving pain. Furthermore, canakinumab and rilonacept reduced the frequency of gout flares compared to the comparators. All three medications were mostly well-tolerated compared to their comparators.
CONCLUSION
IL-1β inhibitors may be a beneficial and safe medication for patients experiencing gout flares for whom current standard therapies are unsuitable.
REVIEW PROTOCOL REGISTRATION
PROSPERO ID: CRD42021267670.
Topics: Adult; Humans; Interleukin Inhibitors; Interleukin-1beta; Interleukin 1 Receptor Antagonist Protein; Gout; Arthritis, Gouty
PubMed: 37491293
DOI: 10.1186/s13075-023-03098-4 -
Rheumatology (Oxford, England) Nov 2019Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these... (Review)
Review
Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reasoning for considering Still's disease as one disease and present anakinra efficacy and safety based on the available literature. The analysis of 27 studies showed that response to anakinra in Still's disease was remarkable, with clinically inactive disease or the equivalent reported for 23-100% of patients. Glucocorticoid reduction and/or stoppage was reported universally across the studies. In studies on paediatric patients where anakinra was used early or as first-line treatment, clinically inactive disease and successful anakinra tapering/stopping occurred in >50% of patients. Overall, current data support targeted therapy with anakinra in Still's disease since it improves clinical outcome, especially if initiated early in the disease course.
Topics: Adult; Antirheumatic Agents; Arthritis, Juvenile; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Patient Safety; Severity of Illness Index; Still's Disease, Adult-Onset; Treatment Outcome
PubMed: 31769856
DOI: 10.1093/rheumatology/kez350 -
Basic & Clinical Pharmacology &... Jun 2023Chemotherapy-induced mucositis, characterized by diarrhoea and villous atrophy, is a severe side effect contributing to reduced quality of life and premature death in...
Chemotherapy-induced mucositis, characterized by diarrhoea and villous atrophy, is a severe side effect contributing to reduced quality of life and premature death in cancer patients treated with cytostatics. Despite its high incidence, there is no effective supportive therapy available. The main objective of this study was to determine if the anti-inflammatory drugs anakinra and/or dexamethasone-which have different mechanisms-of-action-might be used to effectively treat idarubicin-induced mucositis in rats. Mucositis was induced through a single injection with 2 mg/kg idarubicin (with saline as control), followed by daily treatments of anakinra (100 mg/kg/day), dexamethasone (10 mg/kg/day) or both for 3 days. After 72 h, jejunal tissue was collected for morphological, apoptotic and proliferative analyses, and colonic faecal water content and body weight change were determined. The diarrhoea that was induced by idarubicin (from 63.5% to 78.6% water content in faeces) was completely reversed by anakinra alone, and the jejunal villus height reduction by 36% was prevented by a combination of anakinra and dexamethasone. Dexamethasone reduced apoptosis in the jejunal crypts, both alone and in combination with anakinra. These positive effects encouraged further investigations into the use of anakinra and dexamethasone as supportive therapies for chemotherapy-induced intestinal mucositis and diarrhoea.
Topics: Rats; Animals; Mucositis; Interleukin 1 Receptor Antagonist Protein; Idarubicin; Quality of Life; Diarrhea; Antineoplastic Agents; Dexamethasone; Intestinal Mucosa; Fluorouracil
PubMed: 36878867
DOI: 10.1111/bcpt.13851 -
Blood Advances Nov 2023
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Lymphoma, B-Cell
PubMed: 37962875
DOI: 10.1182/bloodadvances.2023011027 -
BioDrugs : Clinical Immunotherapeutics,... Jul 2022Although most patients with acute pericarditis will recover, a minority will have recurrent, debilitating episodes. In these patients, refractory symptoms result in high... (Review)
Review
Although most patients with acute pericarditis will recover, a minority will have recurrent, debilitating episodes. In these patients, refractory symptoms result in high morbidity, and typically require a prolonged duration of anti-inflammatory treatment. Initially, the efficacy of colchicine in both recurrent pericarditis and periodic fever syndromes suggested the central role of the inflammasome in pericarditis. Subsequently, the success of interleukin-1 antagonists in autoinflammatory diseases prompted further investigation in recurrent pericarditis. In current clinical practice, interleukin-1 antagonists include canakinumab, anakinra, and rilonacept. Both anakinra and rilonacept have demonstrated efficacy in randomized trials of patients with recurrent pericarditis. The aim of the current review is to explain the biological rationale for interleukin-1 antagonists in recurrent pericarditis, highlight supporting clinical evidence, and emphasizing future areas of investigation.
Topics: Anti-Inflammatory Agents; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Pericarditis
PubMed: 35639340
DOI: 10.1007/s40259-022-00537-7 -
La Revue de Medecine Interne Apr 2020
Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Child; Colchicine; Drug Therapy, Combination; Drugs, Investigational; France; Humans; Interleukin 1 Receptor Antagonist Protein; Pericarditis; Recurrence; Therapies, Investigational
PubMed: 31874776
DOI: 10.1016/j.revmed.2019.12.008 -
Journal of the American Heart... Oct 2021Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis,... (Review)
Review
Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis, a non-negligible group of patients will fail to achieve complete remission despite treatment and will be challenged by side effects from the chronic use of medications like corticosteroids. The cause of RP remains unknown in the majority of cases, mainly due to a gap in knowledge of its complex pathophysiology. Over the past 2 decades, the interleukin-1 (IL-1) pathway has been uncovered as a key element in the inflammatory cascade, allowing the development of pharmacological targets known as IL-1 inhibitors. This group of medications has emerged as a treatment option for patients with RP colchicine-resistance and steroid dependents. Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. Although further studies are needed to refine therapeutic protocols and taper of concomitant therapies, IL-1 inhibitors, continue to consolidate as part of the pharmacological armamentarium to manage this complex condition with potential use as monotherapy. The aim of this review is to highlight the role of IL-1 pathway in RP and discuss the efficacy, safety, and clinical applicability of IL-1 inhibitors in the treatment of RP based on current evidence.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin Inhibitors; Interleukin-1; Neoplasms; Pericarditis; Quality of Life; Recurrence
PubMed: 34569270
DOI: 10.1161/JAHA.121.021685