Efficacy but side effects of anakinra therapy for chronic refractory gout in a renal transplant recipient with preterminal chronic renal failure

Direz, Guillaume; Noël, Natacha; Guyot, Charlotte; Toupance, Olivier; Salmon, Jean-Hugues; Eschard, Jean-Paul

doi:10.1016/j.jbspin.2012.04.009

Cited by 18 publications

(16 citation statements)

References 7 publications

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“…18 The most common adverse effect is injection site reaction, 19 and infections and neutropenia have also been described; and experience is limited to five years. 17,20 This patient presented a partial response to anakinra, 21 as was the case with 34% of the patients on the Euro fever Registry; 22 C-reactive protein presents fluctuations similar to those already described by other authors. 23 The partial response in our case could be due to starting treatment 30 years after onset of the disease.…”

Section: Discussionsupporting

confidence: 73%

Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Enríquez¹,

Sirvent²,

Padilla³

et al. 2013

Renal Failure

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Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome.A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted.It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.

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Section: Discussionsupporting

confidence: 73%

Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Enríquez¹,

Sirvent²,

Padilla³

et al. 2013

Renal Failure

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“…Gouty arthritis patients treated with anakinra were also in increased risk for infections, mostly by S. aureus [68]. Since IL-1 is a neutrophil attractant and growth factor, the risk for neutropenia in patients treated with anakinra increased as well [77, 78], and during administration of anakinra neutrophil numbers must be followed. Anakinra is forbidden to patients receiving TNF blockers or patients getting live vaccines.…”

Section: Anti-inflammatory Cytokine Biologicsmentioning

confidence: 99%

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

Rider

Carmi

Bar‐Sela

2016

International Journal of Cell Biology

165

111

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Proinflammatory cytokines are potent mediators of numerous biological processes and are tightly regulated in the body. Chronic uncontrolled levels of such cytokines can initiate and derive many pathologies, including incidences of autoimmunity and cancer. Therefore, therapies that regulate the activity of inflammatory cytokines, either by supplementation of anti-inflammatory recombinant cytokines or by neutralizing them by using blocking antibodies, have been extensively used over the past decades. Over the past few years, new innovative biological agents for blocking and regulating cytokine activities have emerged. Here, we review some of the most recent approaches of cytokine targeting, focusing on anti-TNF antibodies or recombinant TNF decoy receptor, recombinant IL-1 receptor antagonist (IL-1Ra) and anti-IL-1 antibodies, anti-IL-6 receptor antibodies, and TH17 targeting antibodies. We discuss their effects as biologic drugs, as evaluated in numerous clinical trials, and highlight their therapeutic potential as well as emphasize their inherent limitations and clinical risks. We suggest that while systemic blocking of proinflammatory cytokines using biological agents can ameliorate disease pathogenesis and progression, it may also abrogate the hosts defense against infections. Moreover, we outline the rational need to develop new therapies, which block inflammatory cytokines only at sites of inflammation, while enabling their function systemically.

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“…There have been further reports of the use of anakinra in difficult to treat cases showing good efficacy, with most patients having a good response within 24 hours. [26][27][28][29][30][31] Anakinra has a good pharmacokinetic profile with a shorter duration of action, accumulation can occur in severe renal failure, 32 and this had been linked to an increased risk of infection in one case report. 31 The dose of a daily 100 mg has been used in studies looking at treatment of rheumatoid arthritis (usually between 50 and 150 mg), and it was well tolerated for up to 3 years.…”

Section: Interleukin-1 Inhibitorsmentioning

confidence: 99%

“…[26][27][28][29][30][31] Anakinra has a good pharmacokinetic profile with a shorter duration of action, accumulation can occur in severe renal failure, 32 and this had been linked to an increased risk of infection in one case report. 31 The dose of a daily 100 mg has been used in studies looking at treatment of rheumatoid arthritis (usually between 50 and 150 mg), and it was well tolerated for up to 3 years. [33][34][35][36][37] The licensed use of anakinra is for Cryopryin Associated Periodic Syndrome where dosing is 3-4 mg/kg in severe disease (doses up to 800 mg).…”

Section: Interleukin-1 Inhibitorsmentioning

confidence: 99%

“…[27][28][29] There was one case report of neutropaenia in one patient with a kidney transplant with severe renal impairment. 31 Blood counts will be checked at the end of treatment at day 5 and participants will also be assessed for infection face to face on day 2, day 7 and 8 weeks, and by telephone contact on day 3, day 4 and day 5. Participants will be asked to stop treatment if serious infection develops.…”

Section: Interleukin-1 Inhibitorsmentioning

confidence: 99%

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Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study

et al. 2017

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IntroductionAcute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD).Methods and analysisASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies.Ethics and disseminationThe London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberEudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614–34090.

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Efficacy but side effects of anakinra therapy for chronic refractory gout in a renal transplant recipient with preterminal chronic renal failure

Cited by 18 publications

References 7 publications

Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Nephrotic Syndrome and AA Amyloidosis Revealing Adult-Onset Cryopyrin-Associated Periodic Syndrome

Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study

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