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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 -
Journal For Immunotherapy of Cancer Jan 2022In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS)...
In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings.
Topics: Adult; Aged; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Neurotoxicity Syndromes; Receptors, Chimeric Antigen
PubMed: 34996813
DOI: 10.1136/jitc-2021-003847 -
Pediatric Blood & Cancer Nov 2020Hemophagocytic lymphohistiocytosis (HLH) can be familial or secondary, which is often triggered by infection or malignancy. HLH therapy includes dexamethasone and...
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) can be familial or secondary, which is often triggered by infection or malignancy. HLH therapy includes dexamethasone and etoposide. However, therapy is associated with significant morbidity and mortality. Anakinra, a recombinant interleukin-1 receptor antagonist, has been reported to treat macrophage activation syndrome (MAS), rheumatic sHLH. We report our experience with anakinra to treat patients with nonrheumatic secondary HLH (sHLH).
PROCEDURE
Six children were diagnosed with HLH from December 2014 to August 2016 and were treated with subcutaneous anakinra (6-10 mg/kg/day divided over four doses) with or without dexamethasone (10 mg/m /day). Therapy was either escalated or weaned based on clinical and laboratory response.
RESULTS
Five of six patients were treated with anakinra and dexamethasone, and one with anakinra alone due to active cytomegalovirus (CMV) pneumonitis. The median age of diagnosis was 1.8 years (range 0.8-14.9 years). No pathogenic mutations associated with HLH were identified, but three of six possessed genetic variants of unknown significance. Infectious triggers were identified for four patients and two patients had malignancies. The average treatment duration was 8 weeks with 3.5-5.5 years of follow up. No patient needed escalation of therapy to include etoposide. All patients achieved remission. Anakinra was well tolerated without significant adverse effects.
CONCLUSION
Initial treatment with anakinra (with or without dexamethasone) is a feasible treatment alternative for patients with secondary HLH and may allow for avoidance of etoposide. We recommend early initiation of anakinra when HLH is suspected. A broader investigation of the use of anakinra as a first-line agent for HLH is ongoing.
Topics: Adolescent; Anti-Inflammatory Agents; Antirheumatic Agents; Child; Child, Preschool; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Interleukin 1 Receptor Antagonist Protein; Lymphohistiocytosis, Hemophagocytic; Male; Prognosis; Retrospective Studies
PubMed: 32725881
DOI: 10.1002/pbc.28581 -
JAMA Dermatology Dec 2022
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Amyloidosis; Familial Mediterranean Fever; Antirheumatic Agents
PubMed: 36223107
DOI: 10.1001/jamadermatol.2022.2124 -
Expert Opinion on Drug Safety Jul 2018The anti-interleukin-1 receptor antagonist, anakinra, was approved for the treatment of rheumatoid arthritis (RA) more than 12 years ago. However, its adverse effects... (Review)
Review
The anti-interleukin-1 receptor antagonist, anakinra, was approved for the treatment of rheumatoid arthritis (RA) more than 12 years ago. However, its adverse effects are not well known. Areas covered: We review the safety profile of anakinra, analyzing clinical trials, observational studies, and registry data. Expert opinion: Due to its lower efficacy compared with other biological therapies approved for RA and its daily subcutaneous administration, anakinra is used only marginally for the treatment of RA. This has limited the experience with this drug in RA, with a lack of data from long-term observational studies or registries. From the five clinical trials performed, and given the unfeasibility of developing new studies of anakinra in RA, it may be concluded that site injection reactions, infections at higher doses (>100 mg), and immunogenicity are the most frequent adverse events related to anakinra administration.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Interleukin 1 Receptor Antagonist Protein; Receptors, Interleukin-1
PubMed: 29883212
DOI: 10.1080/14740338.2018.1486819 -
Arthritis & Rheumatology (Hoboken, N.J.) Jan 2024To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of...
OBJECTIVE
To describe a 41-year-old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin-1 receptor antagonist (IL-1Ra) protein, anakinra, since the age of 28, who presented with golf-ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.
METHODS
Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo-red staining and proteomic evaluation of microdissected Congo red-positive amyloid deposits by liquid chromatography-tandem mass spectrometry.
RESULTS
The skin, stomach, and kidney biopsies all showed the presence of Congo red-positive amyloid deposits. Mass spectrometry-based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL-1Ra protein)-type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P-component) and the amyloidogenic IL-1Ra protein, which were present in Congo red-positive areas and absent in Congo red-negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL-1Ra (anakinra) and not endogenous wild-type IL-1Ra.
CONCLUSION
This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).
Topics: Female; Infant, Newborn; Humans; Adult; Interleukin 1 Receptor Antagonist Protein; Plaque, Amyloid; Congo Red; Proteomics; Amyloidosis
PubMed: 37488949
DOI: 10.1002/art.42664 -
The Journal of Dermatological Treatment Feb 2022Anakinra (Kineret) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease... (Review)
Review
PURPOSE
Anakinra (Kineret) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions.
MATERIALS AND METHODS
The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations.
RESULTS
Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions.
CONCLUSION
Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Dermatology; Hidradenitis Suppurativa; Humans; Infant, Newborn; Interleukin 1 Receptor Antagonist Protein; Off-Label Use; Treatment Outcome
PubMed: 32279586
DOI: 10.1080/09546634.2020.1755417 -
European Journal of Medical Research Feb 2023At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection.
METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection.
RESULTS
We included five RCTs with 1,627 patients (n = 888, n = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64-1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I = 49%; low certainty of evidence).
CONCLUSIONS
Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone.
TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021257552.
Topics: Adult; Humans; Male; Middle Aged; Female; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2
PubMed: 36841793
DOI: 10.1186/s40001-023-01072-z -
European Journal of Preventive... Jun 2020Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade... (Observational Study)
Observational Study
AIMS
Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population.
METHODS AND RESULTS
This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence.
CONCLUSION
In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Colchicine; Drug Administration Schedule; Drug Resistance; Drug Tapering; Female; Humans; Immunologic Factors; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Pericarditis; Recurrence; Registries; Time Factors; Treatment Outcome; Young Adult
PubMed: 31610707
DOI: 10.1177/2047487319879534 -
Medical Sciences (Basel, Switzerland) Dec 2022Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition... (Meta-Analysis)
Meta-Analysis Review
Heart failure (HF) has become increasingly difficult to manage given its increasing incidence. Despite the availability of novel treatment target relieving inhibition and congestions for neurohormonal activation, heart failure is one of leading health conditions associated with high hospitalization and readmission rates, resulting in poor quality of life. In light of this, this article serves to demonstrate the effect of anakinra as one of the treatment paradigms for HF to explore the need for advanced novel interventions. We conducted a search in five electronic databases, including , , , , and , for RCTs (randomized controlled trials) evaluating the effects of anakinra against placebo in HF. Meta-analysis was performed using RevMan version 5.4. Eight RCTs were obtained and included for analysis in this study. The results demonstrate that anakinra significantly reduces the levels of CRP (C-reactive protein), with significant difference between anakinra- and placebo-treated groups. Analyses also show that CRP failed to cause an improvement in peak oxygen consumption and ventilatory efficiency. Additionally, the treatment-related adverse events were insignificant. Some considerable limitations are that the same set of researchers were involved in most of the studies; hence, more independent studies need to be encouraged. Anakinra was associated with a reduction in CRP levels, indicating some anti-inflammatory effects but no effect on function, exercise capacity, and adverse effects.
Topics: Humans; Heart Failure; Hospitalization; Interleukin 1 Receptor Antagonist Protein; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36649041
DOI: 10.3390/medsci11010004