Safety Of Anakinra Research Articles

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations. Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients. From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile. Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.

Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study

Background and objectiveEvidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established.Patients and methodsTo examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children’s hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG + anakinra).ResultsAmong 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG + anakinra group, of which 9 (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG + anakinra group were enriched in a CV shock phenotype (p = 0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG + anakinra group exhibited improvements in fever and cardiac function with or without CS. No significant adverse events were observed, and no differences in IL-1β levels were found among MIS-C patients in the IVIG + anakinra group.ConclusionsAnakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of severe MIS-C.

Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19

COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear. To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation. The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, ≥5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021. Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously. The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-to-treat basis. A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99). In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia. ClinicalTrials.gov Identifier: NCT04443881.

A single-centre retrospective case series of Anakinra for incident calcium pyrophosphate deposition disease.

In this 2-year retrospective case series, we characterise the calcium pyrophosphate deposition disease (CPPD) inpatient cohort at a single centre and assess the efficacy and safety of anakinra in its treatment. Adult inpatients with CPPD between 1st September 2020 and 30th September 2022 were identified by ICD-10 codes and confirmed based on clinical diagnosis and either CPP crystals on aspirate or chondrocalcinosis on imaging. Charts were reviewed for demographic, clinical, biochemical data, treatment choice, and response. Response to treatment was determined from chart documentation and calculated from time of first CPPD treatment. Daily responses to anakinra were recorded if anakinra was used. Seventy patients accounting for 79 cases of CPPD were identified. Twelve cases received anakinra, whilst 67 cases received conventional therapy only. Patient receiving anakinra were predominantly male, had multiple comorbidities, and had higher CRPs and serum creatinine when compared to the non-anakinra group. Anakinra was rapidly effective with the mean time to substantial and complete response being 1.7 and 3.6days respectively. Anakinra was well tolerated. This study adds to the small amount of retrospective data present about the use of anakinra in CPPD. We observed a rapid response to anakinra in our cohort with minimal adverse drug reactions. Key Points • Treatment of CPPD with anakinra appears to be rapidly efficacious without safety concerns.

Effectiveness and safety of anakinra in gouty arthritis: A case series and review of the literature.

Gout is the most common type of inflammatory arthritis. Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are the first-line agents, although they are contraindicated in many patients. Blockade of IL-1 with anakinra can be an alternative. To present a case series of 10 difficult-to-treat gout patients treated with anakinra and perform a scoping review of the effectiveness and safety of anakinra in gout patients. A total of 1,519 citations were screened. The reviewers ran a two-stage screening process by title/abstract and full-text reading. Thirty-eight articles finally met the selection criteria and were included for data extraction and synthesis. Experience in difficult-to treat and complex clinical scenarios, such as active infection, hemodialysis, and transplantation, were specifically described. The study sample comprised 551 patients, from whom 648 flares were finally analyzed. The mean age was 57.9 years, and 82.9% were men. The clinical presentation was polyarticular in 47.5% and tophaceous in 66.9%. Sixty-five patients with an active infection, 41 transplanted patients and 14 in haemodyalisis treated with anakinra are described. More than half of the patients had >1 associated comorbidity. Anakinra was effective both for flares (94%) and for long-term treatment (91%) and well tolerated. In the case of flares, 34 (6.7%) adverse effects were registered. Adverse events were more prevalent in long-term treatment. Anakinra was effective and safe for management of gout flares in difficult-to-treat patients. It has been used in multiple complex scenarios, such as active infections, dialysis, transplantation, chronic kidney disease, and polyarticular gout. Anakinra has also proven effective as long-term treatment, although there are more concerns about its safety.

Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score-matched cohort study.

Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting. In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n=36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes. All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4%vs 0%) (P=.005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P=.448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P=.014 and P<.001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P=.058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P<.001), and eGFR (P=.004), hsCRP (P<.001) and ESR (P=.026) levels were lower throughout the follow-up, whereas proteinuria levels were not. Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.

Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Prospects of anti-inflammatory and urate-lowering therapy of gout: A vector from the past to the future

The article provides an overview of new and promising drugs aimed at anti-inflammatory and urate-lowering therapy of gout, both already registered and used in clinical practice, and at the stages of implementation or clinical research and demonstrating their high efficacy and safety. Modern views and approaches to the treatment of gout, reflected in foreign and domestic clinical recommendations, are shown. Emphasis is placed on the safety and efficacy of colchicine in gouty arthritis and its cardioprotective properties in comorbid patients suffering from gout in combination with cardiovascular pathology. Information is provided on the effectiveness of new anti-inflammatory drugs for symptomatic therapy of gout: kanakinumab, according to the experience of which our country occupies a leading position in Europe. The efficacy and safety of anakinra allows us to consider the drug as an effective alternative to the traditional approach to antiinflammatory therapy of gout. Rilonacept provides doctors with more potential treatment algorithms in a population of patients with gout that is difficult to treat with traditional treatment. The historical data on the use of adrenocorticotropic hormone as an anti-inflammatory agent in gout are given. Information on reserve, new and promising urate-lowering drugs is provided. The focus is on the safety and efficacy of febuxostat, based on the results of recent large randomized clinical trials. Other drugs that reduce the level of uric acid in the blood plasma are considered: uricosuric agents (probenecid, benzbromarone, sulfinpyrazone, lezinurad, verinurad, dotinurad and archalophenate), xanthine oxidase inhibitors (allopurinol and topiroxostat), pegylated uricase preparations (pegloticase and rasburicase), which can be considered in the future as reserve drugs with the possibility of combined applications with the main means for urate-lowering therapy.

A randomized controlled clinical trial on efficacy and safety of anakinra in patients with severe COVID-19.

IntroductionHyperinflammatory state has a role in the pathogenesis of COVID‐19. Anakinra could reduce inflammation and help to combat the condition. In this study, we aimed to assess the safety and efficacy of anakinra (PerkinRA®) in severe COVID‐19.MethodThe study was an open‐label, randomized, controlled trial conducted in Imam Hossein Medical Center from May to July 2020. Patients with a confirmed diagnosis of COVID‐19 were included in this study. We administered anakinra 100 mg daily intravenously. All patients received COVID‐19 pharmacotherapy based on the represented national guideline. The need for invasive mechanical ventilation is considered the primary outcome.ResultsThirty patients were included in this study, and 15 of them received Anakinra. Nineteen patients were male (63.3%), and 11 were female (36.7%). The mean age of patients was 55.77 ± 15.89 years. In the intervention group, the need for invasive mechanical ventilation was significantly reduced compared to the control group (20.0% vs. 66.7%, p = .010). Also, these patients had a significantly lower length of hospital stay (p = .043). No significant higher rate of infection was recorded.ConclusionAnakinra as an immunomodulatory agent has been associated with the reduced need for mechanical ventilation in patients admitted to intensive care units because of severe COVID‐19. The medication reduced the hospital length of stay. Furthermore, no increased risk of infection was observed. Further randomized placebo‐controlled trials with a larger sample size are needed to confirm these findings.

Long-term safety and efficacy of anakinra and canakinumab in patients with familial Mediterranean fever: a single-centre real-life study with 101 patients.

Anakinra and canakinumab are the most commonly used agents in colchicine resistant/intolerant patients. In this study we investigated long-term efficacy and safety of anakinra and canakinumab. In this retrospective study, we enrolled 101 adult patients with familial Mediterranean fever (FMF). Clinical and laboratory parameters before and after treatment with anakinra/canakinumab and the side effects observed during the treatment were recorded. All patients received anakinra initially and switched to canakinumab, in case of inadequate response/intolerance. The median (IQR) duration of treatment with anti-IL-1 agents was 35 (24-47.5) months. 101 patients were treated with anakinra and 27 patients with canakinumab. The autoinflammatory diseases activity and attacks decreased with both anakinra and canakinumab. Anakinra was effective in decreasing proteinuria and canakinumab was not effective in decreasing proteinuria in anakinra unresponsive patients. The modified FMF score was achieved in 76.2% of anakinra and 88.9% of canakinumab group. Injection site reactions (ISRs, n:15) was the most common reason of discontinuation of anakinra and most of ISRs developed in first 3 months of treatment. One severe skin rash, two anaphylactic reactions and one severe neutropenia were observed with anakinra; in the first, eighth, twelfth and fiftieth months, respectively. No severe side effects or side effect-related discontinuation of canakinumab were observed. Anakinra and canakinumab seem to be effective in long-term management of FMF patients. Canakinumab had a favourable safety/tolerability profile. Anakinra is also generally safe, but the serious side effects that may be observed in the short and long-term use should be taken into account.

Anti-interleukin-1 agents for pericarditis: a primer for cardiologists.

Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1β are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1β (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor ‘trap’, binding both IL-1α and IL-1β), and canakinumab (human monoclonal anti-IL-1β antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low (<4%). The most common reported side effect is injection site reactions (>50% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years.

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.

EMA assessing safety of anakinra in adults with COVID-19

EMA assessing safety of anakinra in adults with COVID-19

Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis.

BackgroundAcute respiratory distress syndrome and cytokine release syndrome are the major complications of coronavirus disease 2019 (COVID-19) associated with increased mortality risk.ObjectivesWe performed a meta-analysis to assess the efficacy and safety of anakinra in adult hospitalized non-intubated patients with COVID-19.Search methodsRelevant trials were identified by searching literature until 24 April 2021 using the following terms: anakinra, interleukin 1, coronavirus, COVID-19, SARS-CoV-2.Selection criteriaTrials evaluating the effect of anakinra on the need for invasive mechanical ventilation and mortality in hospitalized non-intubated patients with COVID-19.ResultsNine studies (n = 1,119) were eligible for inclusion in the present meta-analysis. Their bias risk with reference to the assessed parameters was high. In pooled analyses, anakinra reduced the need for invasive mechanical ventilation (odds ratio, OR: 0·38, 95% confidence interval, CI: 0·17–0·85, p= 0.02, I2=67%; 6 studies, n = 587) and mortality risk (OR: 0·32, 95% CI: 0·23–0·45, p< 0·00001, I2=0%; 9 studies, n = 1,119) compared with standard of care therapy. There were no differences regarding the risk of adverse events, including liver dysfunction (OR: 0·75, 95% CI: 0·48–1·16, p> 0·05, I2=28%; 5 studies, n = 591) and bacteremia (OR: 1·07, 95% CI: 0·42–2·73, p> 0·05, I2=71%; 6 studies, n = 727).ConclusionsAvailable evidence shows that treatment with anakinra reduces both the need for invasive mechanical ventilation and mortality risk of hospitalized non-intubated patients with COVID-19 without increasing the risk of adverse events. Confirmation of efficacy and safety requires randomized placebo-controlled trials.

The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis.

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 - 0.54, I2 = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 - 0.95, I2 = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 - 3.91, I2 = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 - 3.03, I2 = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.

Anakinra for constrictive pericarditis associated with incessant or recurrent pericarditis

ObjectiveFrequent flares of pericardial inflammation in recurrent or incessant pericarditis with corticosteroid dependence and colchicine resistance may represent a risk factor for constrictive pericarditis (CP). This study was aimed at...

Anakinra in Recurrent Pericarditis: Current Evidence on Clinical Use, Effectiveness, and Safety.

Anakinra is a recombinant human interleukin 1 receptor antagonist that competes and blocks the biologic effects of interleukin 1, reducing systemic inflammatory responses. In the 2015 guidelines for the diagnosis and management of pericardial diseases of the European Society of Cardiology, anakinra was established as a third-line therapy option for refractory recurrent pericarditis (RP). Recently, important studies that investigates the effect and safety of anakinra in RP were published, such as the AIRTRIP trial and the International Registry of Anakinra for Pericarditis. This article presents the current evidence about the effectiveness and safety of anakinra in RP and discusses its clinical application and mechanisms.

AB1059 A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ANAKINRA IN PATIENTS WITH STILL´S DISEASE

Background:Adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) are rare autoinflammatory disorders associated with an activated IL-1 pathway, characterized by spiking fever, rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. There is a growing understanding that SJIA and AOSD are one disease with different ages of onset, i.e. Still’s disease. The anaSTILLs study (anakinra inStill´sdisease) was designed to further evaluate efficacy and safety of anakinra in patients with Still´s disease across all age groups.Objectives:The primary objective was to demonstrate efficacy of anakinra versus placebo as assessed by ACR30 response with absence of fever at Week 2. Secondary objectives included: early onset of efficacy, sustained efficacy, time to study drug discontinuation, safety, pharmacokinetics, clinical signs and biomarkers.Methods:‘anaSTILLs’ was a randomized, double-blind, placebo-controlled, 12-week study including patients with active and newly diagnosed (6 months) Still´s disease according to adapted ILAR criteria if &lt;16, or Yamaguchi criteria, if ≥16 years of age at disease onset. Patients were randomized to anakinra 2 mg/kg (max 100 mg/day), 4 mg/kg (max 200 mg/day) or placebo.Results:12 patients were randomized and received study drug: 6 anakinra (2 mg/kg n=2, 4 mg/kg n=4) and 6 placebo, the study was terminated early due to slow recruitment. 1 patient on placebo had lymphoma, not Still’s disease, and was excluded; thus in total 11 patients were analyzed for efficacy, 8 were children [median (range) age=4.0 (1-11) years] and 3 were adults [median (range) age=32.0 (25-51) years]. 55% were male and the mean symptom duration was 74.2 days. All patients on anakinra but none on placebo achieved ACR30 response with absence of fever at Week 2 (p-value=0.0022). The efficacy of anakinra was further demonstrated by superiority to placebo in ACR50/70/90 responses with absence of fever at Week 2. All placebo patients discontinued the study within 6 weeks, 2 due to progressive disease, 2 due to lack of efficacy and 1 due to withdrawal by patient. There was a numerically higher proportion with early onset of efficacy (Week 1) in the anakinra group compared to placebo. The ACR30/50/70/90 responses in the anakinra group were sustained throughout the study period. Patients in the anakinra group had a prompt and persistent decrease in CRP and ferritin levels at Week 1, which was not observed in the placebo group. There were no unexpected safety findings. All anakinra patients developed anti-drug antibodies (ADAs) at some timepoint during the study. ADAs were persistent throughout the treatment period, except in one patient. Titers were low to moderate. One placebo patient had low ADA titers at one occasion. No neutralizing antibodies were observed and the ADAs did not appear to impact clinical efficacy or safety.Conclusion:Anakinra is superior to placebo in the treatment of Still’s disease. ADAs occur frequently but do not appear to adversely impact efficacy or safety. These results confirm the benefits of anakinra treatment in patients with active, newly diagnosed Still´s disease across ages.Disclosure of Interests:Laura Schanberg Grant/research support from: Sobi, BMS, Consultant of: Aurinia, UCB, Sanofi, Peter Nigrovic Grant/research support from: Novartis, BMS, Pfizer, Consultant of: Novartis, BMS, Pfizer, Sobi, Miach Orthopedics, Simcere, XBiotech, Quench Bio, Ashley Cooper: None declared, Winn Chatham Grant/research support from: Sobi, Consultant of: Sobi, Shoghik Akoghlanian: None declared, Namrata Singh: None declared, Egla Rabinovich Grant/research support from: AbbVie, UCB Pharma, Janssen Research &amp; Development, Akaluck Thatayatikom: None declared, Alysha Taxter: None declared, Jonathan Hausmann Consultant of: Novartis, Milan Zdravkovic Shareholder of: Sobi, Employee of: Sobi, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Henrik Andersson Employee of: Sobi, Susanna Cederholm Shareholder of: Sobi, Employee of: Sobi, Margareta Wikén Shareholder of: Sobi, Employee of: Former employee of Sobi, Rayfel Schneider Grant/research support from: Roche, Novartis, Sobi, Pfizer, Consultant of: Sobi, Novartis, Novimmune, Fabrizio De Benedetti Grant/research support from: AbbVie, Pfizer, Novartis, Novimmune, Sobi, Sanofi, Roche, Speakers bureau: AbbVie, Novartis, Roche, Sobi

Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study.

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. 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%; P < 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. In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.

Anakinra for the treatment of acute gout flares: a randomized, double-blind, placebo-controlled, active-comparator, non-inferiority trial.

To evaluate the efficacy and safety of anakinra in treating acute gout flares in a randomized, double-blind, placebo-controlled, active comparator, non-inferiority (NI) trial. Patients with a crystal-proven acute gout flare were randomized (1: 1) to treatment with anakinra or treatment as usual (free choice: either colchicine, naproxen or prednisone). The primary end point was the change in pain between baseline and the averaged pain score on days 2-4 measured on a five-point rating scale. NI of anakinra would be established if the upper bound of the 95% CI of the numeric difference in changed pain scores between treatment groups did not exceed the NI limit of 0.4 in favour of treatment as usual, in the per-protocol (PP) and intention-to-treat (ITT) populations, assessed in an analysis of covariance model. Secondary outcomes included safety assessments, improvement in pain, swelling, tenderness and treatment response after 5 days, assessed using linear mixed models and binary logistic regression models. Forty-three patients received anakinra and 45 treatment as usual. Anakinra was non-inferior (mean difference; 95% CI) to treatment as usual in both the PP (-0.13; -0.44, 0.18) and ITT (-0.18; -0.44, 0.08) populations. No unexpected or uncommon (serious) adverse events were observed in either treatment arm. Analyses of secondary outcomes showed that patients in both groups reported similar significant reductions in their gout symptoms. Efficacy of anakinra was shown to be non-inferior to treatment as usual for the treatment of acute gout flares, suggesting that anakinra is an effective treatment alternative for acute gout flares. Het Nederlands Trial Register, www.trialregister.nl, NTR5234.