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Open Heart Mar 2024Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and... (Observational Study)
Observational Study
AIM
Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone.
METHODS
International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence.
RESULTS
A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021).
CONCLUSIONS
The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.
Topics: Female; Humans; Adult; Middle Aged; Male; Interleukin 1 Receptor Antagonist Protein; Retrospective Studies; Colchicine; Adrenal Cortex Hormones; Pericarditis; Interleukin-1
PubMed: 38490715
DOI: 10.1136/openhrt-2023-002599 -
Clinical and Experimental Rheumatology Sep 2022
Topics: Adult; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Humans; Interleukin 1 Receptor Antagonist Protein; Still's Disease, Adult-Onset
PubMed: 35349406
DOI: 10.55563/clinexprheumatol/iqdzl9 -
Pediatric Rheumatology Online Journal Aug 2022Biological treatment and treat-to-target approaches guide the achievement of inactive disease and clinical remission in Autoinflammatory Diseases (AID). However, there... (Review)
Review
BACKGROUND
Biological treatment and treat-to-target approaches guide the achievement of inactive disease and clinical remission in Autoinflammatory Diseases (AID). However, there is limited evidence addressing optimal tapering strategies and/or discontinuation of biological treatment in AID. This study evaluates available evidence of tapering biological treatment and explores key factors for successful tapering.
METHODS
A systematic literature search was conducted in Embase, MEDLINE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials using the OVID platform (1990-08/2020). Bibliographic search of relevant reviews was also performed. Studies/case series (n ≥ 5) in AID patients aged ≤ 18 years with biological treatment providing information on tapering/treatment discontinuation were included. After quality assessment aggregated data were extracted and synthesized. Tapering strategies were explored.
RESULTS
A total of 6035 records were identified. Four papers were deemed high quality, all focused on systemic juvenile idiopathic arthritis (sJIA) (1 open-label randomized trial, 2 prospective, 1 retrospective observational study). Biological treatment included anakinra (n = 2), canakinumab (n = 1) and tocilizumab (n = 1). Strategies in anakinra tapering included alternate-day regimen. Canakinumab tapering was performed randomized for dose reduction or interval prolongation, whereas tocilizumab was tapered by interval prolongation. Key factors identified included early start of biological treatment and sustained inactive disease.
CONCLUSION
Tapering of biological treatment after sustained inactive disease should be considered. Guidance for optimal strategies is limited. Future studies may leverage therapeutic drug monitoring in combination with pharmacometric modelling to further enhance personalized "taper-to-target" strategies respecting individual patients and diseases aspects.
Topics: Antirheumatic Agents; Hereditary Autoinflammatory Diseases; Humans; Interleukin 1 Receptor Antagonist Protein; Observational Studies as Topic; Prospective Studies; Systematic Reviews as Topic
PubMed: 35964053
DOI: 10.1186/s12969-022-00725-3 -
European Heart Journal. Cardiovascular... Jan 2018Pericarditis is a debilitating condition that results from profound inflammation of the pericardial tissue. Between 10 and 15% of first episodes of acute pericarditis... (Review)
Review
Pericarditis is a debilitating condition that results from profound inflammation of the pericardial tissue. Between 10 and 15% of first episodes of acute pericarditis will be followed by several episodes refractory to conventional treatment. Current standard of care for pericarditis treatment includes high-dose non-steroidal anti-inflammatory drugs, colchicine, and systemic corticosteroids, each associated with potentially severe toxicities and nominal efficacy. Interleukin-1 (IL-1), an apical pro-inflammatory cytokine, plays an important role as an autocrine magnifier of systemic inflammation in pericarditis. Interruption of the IL-1 circuit has been shown to have a favourable risk profile in several disease states. In this review, we discuss the growing body of evidence which supports the use of IL-1 blockade in the treatment of recurrent pericarditis as well as provide practical considerations for the use of IL-1 blockade in clinical practice.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Pericarditis
PubMed: 28633474
DOI: 10.1093/ehjcvp/pvx018 -
European Journal of Pharmacology Jun 2022To assess which immunosuppressive drugs have been investigated and proven efficacious in patients with cardiovascular disease (CVD) or type 2 diabetes (T2D) without... (Review)
Review
OBJECTIVE
To assess which immunosuppressive drugs have been investigated and proven efficacious in patients with cardiovascular disease (CVD) or type 2 diabetes (T2D) without preexisting immune mediated disorders to validate in vitro and animal model findings on low grade inflammation (bedside-to-bench).
METHODS
Clinical trials on immunosuppressive drugs in CVD or T2D were found in PubMed. Studies on patients with preexisting immune mediated inflammatory disease were excluded. A total of 19 clinical trials testing canakinumab, anakinra, methotrexate, colchicine, hydroxychloroquine, etanercept and sulfasalazine were found.
RESULTS
Canakinumab and colchicine significantly reduced the risk of CVD, whereas methotrexate did not. Sulfasalazine showed no effect on vascular function. Anakinra and hydroxychloroquine had a positive effect on glycemic control and β-cell function in T2D. Etanercept had no effect in patients with T2D.
CONCLUSION
The observed results indicate that immunosuppressive drugs specifically targeting IL-1β hold promise for dampening CVD and T2D. These findings validate in vitro and animal models showing involvement of the IL-1-axis in the pathogenesis of CVD and T2D. The use of immunosuppressive drugs targeting the chronic inflammation in these diseases could be a possible future treatment strategy as an add-on to the existing pharmacological treatment of CVD and T2D. However, potential treatment effects, adverse events and cost-effectiveness should be carefully considered with importance for drug development.
Topics: Animals; Antibodies, Monoclonal, Humanized; Cardiovascular Diseases; Colchicine; Diabetes Mellitus, Type 2; Etanercept; Humans; Hydroxychloroquine; Immunomodulating Agents; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-1beta; Methotrexate; Sulfasalazine
PubMed: 35533739
DOI: 10.1016/j.ejphar.2022.174998 -
Neurotherapeutics : the Journal of the... Oct 2023Traumatic brain injury is a common type of acquired brain injury of varying severity carrying potentially deleterious consequences for the afflicted individuals,... (Review)
Review
Traumatic brain injury is a common type of acquired brain injury of varying severity carrying potentially deleterious consequences for the afflicted individuals, families, and society. Following the initial, traumatically induced insult, cellular injury processes ensue. These are believed to be amenable to treatment. Among such injuries, neuroinflammation has gained interest and has become a specific focus for both experimental and clinical researchers. Neuroinflammation is elicited almost immediately following trauma, and extend for a long time, possibly for years, after the primary injury. In the acute phase, the inflammatory response is characterized by innate mechanisms such as the activation of microglia which among else mediates cytokine production. Among the earliest cytokines to emerge are the interleukin- (IL-) 1 family members, comprising, for example, the agonist IL-1β and its competitive antagonist, IL-1 receptor antagonist (IL-1ra). Because of its early emergence following trauma and its increased concentrations also after human TBI, IL-1 has been hypothesized to be a tractable treatment target following TBI. Ample experimental data supports this, and demonstrates restored neurological behavior, diminished lesion zones, and an attenuated inflammatory response following IL-1 modulation either through IL-1 knock-out experiments, IL-1β inhibition, or IL-1ra treatment. Of these, IL-1ra treatment is likely the most physiological. In addition, recombinant human IL-1ra (anakinra) is already approved for utilization across a few rheumatologic disorders. As of today, one randomized clinical controlled trial has utilized IL-1ra inhibition as an intervention and demonstrated its safety. Further clinical trials powered for patient outcome are needed in order to demonstrate efficacy. In this review, we summarize IL-1 biology in relation to acute neuroinflammatory processes following TBI with a particular focus on current evidence for IL-1ra treatment both in the experimental and clinical context.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Neuroinflammatory Diseases; Brain Injuries, Traumatic; Brain Injuries; Receptors, Interleukin-1
PubMed: 37610701
DOI: 10.1007/s13311-023-01421-0 -
PloS One 2023To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the...
Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study.
OBJECTIVE
To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described.
METHODS
Retrospective cohort study of 312 patients admitted to Hospital Clínico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day).
RESULTS
The median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO2/FiO2) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination. A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution.
CONCLUSIONS
Early treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.
Topics: Humans; Male; Aged; Female; SARS-CoV-2; COVID-19; Interleukin 1 Receptor Antagonist Protein; Retrospective Studies; Adrenal Cortex Hormones; Treatment Outcome
PubMed: 36961847
DOI: 10.1371/journal.pone.0283529 -
Annals of Clinical and Translational... Jan 2022Refractory cerebral autoinflammatory-autoimmune diseases are often associated with dysregulated innate immunity and are targeted by anakinra, an interleukin-1 receptor...
Refractory cerebral autoinflammatory-autoimmune diseases are often associated with dysregulated innate immunity and are targeted by anakinra, an interleukin-1 receptor antagonist. We analyzed the therapeutic effect of anakinra in refractory cerebral autoinflammatory response (CAIR) at a single institution from January 2017 to May 2021. In total, 12 patients with various etiologies were sympathetically treated with anakinra (100 mg/day subcutaneously). Four patients showed good responses, and among these patients, three patients had pathologically demonstrated CAIR. The other eight patients were nonresponsive. No patient had a serious adverse effect. Thus, anakinra may be a therapeutic option for refractory cerebral autoinflammatory diseases.
Topics: Adult; Anti-Inflammatory Agents; Autoimmune Diseases of the Nervous System; Brain Diseases; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Neuroinflammatory Diseases; Recurrence; Treatment Outcome; Young Adult
PubMed: 35040583
DOI: 10.1002/acn3.51500 -
Biochemical Pharmacology Jul 2020Cardiovascular disease remains - despite the development of new drugs, devices, and therapeutic strategies - the leading cause of death and disability worldwide. There... (Review)
Review
Cardiovascular disease remains - despite the development of new drugs, devices, and therapeutic strategies - the leading cause of death and disability worldwide. There is therefore a great need to implement the pharmacological armamentarium, considering also the need to balance the therapeutic and the side effects. Furthermore, the best choice among the drug treatment options and reduction of side effects remain urgent problems for studies of cardiovascular disease. In this context, drug repurposing could be an innovative way and opportunity to extend and improve pharmacological tools. Indeed, applying well-established drugs and compounds to new indications, drug repurposing has already been proven efficient and safe in humans. Furthermore, this approach generates lower costs and needs shorter time for approval than the development of a de novo drug. In the current review, we discuss the main evidence for the repurposing in cardiovascular diseases of drugs approved and marketed for other pathologies by reviewing their mechanisms of action and the results reported in observational and then in randomized studies.
Topics: Antibodies, Monoclonal; Cardiovascular Diseases; Cholinesterase Inhibitors; Colchicine; Cytokines; Drug Repositioning; Glucagon-Like Peptide-1 Receptor; Humans; Interleukin 1 Receptor Antagonist Protein; Metformin; Methotrexate; Phosphodiesterase 5 Inhibitors; Xanthine Oxidase
PubMed: 32142728
DOI: 10.1016/j.bcp.2020.113894 -
Inflammopharmacology Apr 2023In COVID-19, severe disease course such as need of intensive care unit (ICU) as well as development of mortality is mainly due to cytokine storm. In this study, we aimed... (Observational Study)
Observational Study
BACKGROUND
In COVID-19, severe disease course such as need of intensive care unit (ICU) as well as development of mortality is mainly due to cytokine storm. In this study, we aimed to evaluate the high-dose intravenous anakinra treatment response and outcome in patients with severe and critically ill COVID-19 compared to standard of care.
METHODS
This retrospective observational study was carried out at a tertiary referral center. The study population consisted of two groups as follows: the patients receiving high-dose intravenous anakinra (anakinra group) between 01.09.2021 and 01.02.2022 and the patients treated with standard of care (SoC, control group) as historical control group who were hospitalized between 01.07.2021 and 01.09.2021.
RESULTS
After the propensity score 1:1 matching, 79 patients in anakinra and 79 patients in SoC matched and were included into the analysis. Mean ± SD patient age was 67.4 ± 16.7 and 67.1 ± 16.3 years in anakinra and SoC groups, respectively (p = 0.9). Male gender was 38 (48.7%) in anakinra and 36 (46.2%) in SoC (p = 0.8). Overall, ICU admission was in 14.1% (n = 11) and 30.8% (n = 24) (p = 0.013; OR 6.2), intubation in 12.8% (n = 10) and 16.7% (n = 13) patients (p = 0.5), and 14.1% (n = 11) and 32.1% (n = 25) patients died in anakinra and control groups, respectively (p = 0.008; OR 7.1).
CONCLUSION
In our study, mortality was lower in patients receiving anakinra compared to SoC. Intravenous high-dose anakinra is safe and effective treatment in patients with severe and critical COVID-19.
Topics: Humans; Male; Middle Aged; Aged; Aged, 80 and over; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2; Propensity Score; Retrospective Studies
PubMed: 36707494
DOI: 10.1007/s10787-023-01138-8