Anakinra for the treatment of acute severe gout in critically ill patients
Introduction
Gout is a chronic, episodic inflammatory disease characterized by intra-articular deposition of monosodium urate crystals resulting in monoarticular or polyarticular arthritis. Acute gouty flares are not uncommon in hospitalized patients. Treatment with traditional anti-inflammatory therapies—non-steroidal anti-inflammatory drugs (NSAID), colchicine, and systemic or intra-articular corticosteroids—can be limited by relative and absolute contraindications in the acutely ill patient, especially in the case of elderly patients. NSAID have well established renal and bleeding complications. Systemic steroid therapy may cause impairment in wound healing (which is of particular concern in surgical patients), immunosuppression, hyperglycemia, mood disturbance, myopathy, and insomnia. Colchicine frequently causes gastrointestinal adverse reactions, especially in the setting of renal impairment.
The inflammatory mechanism of gout begins with formation and deposition of monosodium urate crystals into the intra-articular space. This crystal deposition activates the NALP3 inflammasome, which is responsible for binding and activation of caspase I. This enzyme catalyzes the cleavage of pro-IL-1β to the mature IL-1β [1]. IL-1β is a pro-inflammatory cytokine which is involved in multiple inflammatory pathways that ultimately lead to the production of Tumor Necrosis Factor, IL-6, prostaglandin E2, nitric oxide, and adhesion molecules that are involved in articular inflammation [2]. This inflammatory cascade is counterbalanced by a naturally occurring IL-1β receptor antagonist, produced by macrophages, which competitively binds to the IL-1β receptor.
Several studies have described the use of IL-1 receptor antagonism with anakinra in cases of acute gout flares. These studies have been fairly small in size but have shown a significant improvement in acute gout symptoms after treatment with anakinra, a recombinant IL-1 receptor antagonist, as well as good tolerability [3], [4], [5], [6]. One study has reported on the use of anakinra in hospitalized patients with comorbid medical conditions [3], but there are no reports of its use specifically in critically ill patients. We describe the efficacy and tolerability of anakinra in 13 critically ill patients with acute gout flares.
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Materials and methods
We performed a retrospective chart review of a total of 13 hospitalized patients treated with anakinra for acute gouty arthritis at a single health plan and institution (HealthPartners Medical Group and Regions Hospital) between 2009 and 2014. Patients were identified by searching the electronic medical record for the term anakinra. Patients treated with anakinra for diagnoses other than acute gouty arthritis were excluded from the study. The diagnosis of acute gouty arthritis was confirmed by
Results
A total of 13 patients were treated with anakinra for 20 episodes of acute gouty arthritis—12 males and 1 female with a mean age of 58 years (range: 41–70). All patients were critically ill with multiple comorbidities. Of the patients, 10 (77%) were in the Medical Intensive Care Unit, 1 was in the Burn Unit for extensive 3rd degree burns requiring multiple surgeries, 1 was critically ill with a new diagnosis of hemophagocytic lymphohistiocytosis (HLH), and 1 was critically ill in isolation with
Discussion
Treatment of severe gout in critically ill patients with serious comorbid conditions such as sepsis and renal failure can be challenging. Routinely used medications such as non-steroidal anti-inflammatory drugs, colchicine, and corticosteroids may be totally or relatively contraindicated. We present our experience that anakinra can be a safe and efficacious treatment for acute gouty arthritis in critically ill patients with multiple comorbidities who have contraindications or incomplete
Conclusion
While this was a non-randomized, observational, retrospective review of our experience with anakinra at a single large institution, our experience suggests that anakinra is a therapeutic option for acute gout in medically complex, critically ill patients even with serious infections and renal insufficiency where other treatment modalities cannot be used.
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Interleukin-1β converting enzyme (ICE): A comprehensive review on discovery and development of caspase-1 inhibitors
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2021, International ImmunopharmacologyCitation Excerpt :Currently, multiple biologic agents targeting IL-1β are being used to prevent NLRP3-associated diseases. The IL-1R antagonist Anakinra has been demonstrated to effectively treat cryopyrin-associated periodic syndrome, an autoinflammatory syndrome [9], and acute gout flares [10,11]. Therapy with the human IL-1β antibody canakinumab resulted in remarkably lower rates of cardiovascular disease, arthritis, and gout in clinical trials [12].
Effectiveness and safety of anakinra in gout patients with stage 4-5 chronic kidney disease or kidney transplantation: A multicentre, retrospective study
2019, Revue du Rhumatisme (Edition Francaise)Biological Modifiers of Inflammatory Diseases
2019, Clinical Immunology: Principles and PracticeEffectiveness and safety of anakinra in gout patients with stage 4–5 chronic kidney disease or kidney transplantation: A multicentre, retrospective study
2018, Joint Bone SpineCitation Excerpt :No serious AEs occurred, and her renal function remained stable, even with an initial AKN regimen of 200 mg/day. For the gout indication, a single case series reported a good safety profile for AKN in cases of renal insufficiency of various severity [29]; moreover, AKN did not appear to worsen pre-existing infections or affect the response to antibiotics. The management of acute gout remains challenging in patients with stage 4–5 CKD.
This study was performed without financial support.