Canakinumab for the treatment of adult-onset Still’s disease

ABSTRACT

Introduction: Adult-onset Still’s disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology, with clinical and biological similarities with the juvenile form (sJIA).

The pivotal role of interleukin (IL)-1 gives rise to the use of IL-1 inhibitors in treating resistant cases.

Areas covered: This review focuses on canakinumab, a fully human anti-IL-1β antibody, as treatment for AOSD. The data obtained from case reports and case series on AOSD and two double-blind, randomized, placebo-controlled Phase III trial on sJIA are analyzed. Efficacy and safety profiles of canakinumab are discussed.

Expert opinion: There is no unanimous consensus on how to treat with IL-1 inhibitors. Many reviews have focused primarily on anakinra, but the accumulating data for canakinumab have emerged. The choice of treatment is a relevant issue for patients and the national health services. The available data for canakinumab indicate that this drug in AOSD patients is effective and well tolerated.     

An unusual urticarial eruption: Familial cold autoinflammatory syndrome

This is a case of a 26‐year‐old Caucasian woman with a lifelong history of an episodic urticaria associated with arthralgia, precipitated by exposure to cold. She had no other significant past medical history. She reported several family members with a history of very similar episodic eruptions without definitive diagnoses. An examination showed an urticarial eruption over her limbs with no other systemic findings. A baseline full blood examination, serology and autoimmune screen were normal. A skin biopsy was consistent with urticaria, with dermal oedema and a perivascular infiltrate. Following genetic testing, she was found to be heterozygous for a mutation, p.Ala439Val in the NLRP3 gene, known to cause familial cold autoinflammatory syndrome (FCAS), which typically presents with urticaria, conjunctivitis and arthralgia, as described in this patient. FCAS is one subtype of a group of conditions known as cryopyrin‐associated periodic syndromes (CAPS). CAPS are rare, autosomal dominant inherited conditions with a spectrum of phenotypes, characterised by increased interleukin‐1β release with subsequent local and systemic proinflammatory and pyrogenic effects.     

Patients diagnosed with COVID-19 and treated with anakinra: a real-world study in the USA

Anakinra, a recombinant, non-glycosylated human interleukin (IL)-1 receptor antagonist, has been used in real-world clinical practice to manage hyperinflammation in coronavirus disease 2019 (COVID-19). This retrospective, observational study analyses US hospital inpatient data of patients diagnosed with moderate/severe COVID-19 and treated with anakinra between 1 April and 31 August 2020. Of the 119 patients included in the analysis, 63.9% were male, 48.6% were of black ethnicity, and the mean (standard deviation [SD]) age was 64.7 (12.5) years. Mean (SD) time from hospital admission to anakinra initiation was 7.3 (6.1) days. Following anakinra initiation, 73.1% of patients received antibiotics, 55.5% received antithrombotics, and 91.0% received corticosteroids. Overall, 64.7% of patients required intensive care unit (ICU) admittance, and 28.6% received mechanical ventilation following admission. Patients who did not require ICU admittance or who were discharged alive experienced a significantly shorter time between hospital admission and receiving anakinra treatment compared with those admitted to the ICU (5 vs. 8 days; P = 0.002) or those who died in hospital (6 vs. 9 days; P = 0.01). Patients with myocardial infarction or renal conditions were six times (P < 0.01) and three times (P = 0.01), respectively, more likely to die in hospital than be discharged alive. A longer time from hospital admission until anakinra treatment was associated with significantly higher mortality (P = 0.01). Findings from this real-world study suggest that a shorter time from hospital admission to anakinra treatment is associated with significantly lower ICU admissions and mortality among patients with moderate/severe COVID-19.     

IL-1 receptor antagonist,anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.     

Use of anti-inflammatory agents in clinical islet cell transplants: A qualitative systematic analysis

Immunologic and non-immunologic loss of islet cells upon their transplantation into the liver leads to suboptimal outcomes. Anti-inflammatory agents are used during autologous and allogeneic transplantation. The aim of this qualitative systematic literature review is to evaluate their clinical use and safety. Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, ClinicalTrials.gov, and EU Clinical Trials Register were searched. Of the 216 unique citations, 10 with tumor necrosis factor (TNF) blockers [etanercept (ETA) or infliximab] and 3 with both TNF blockers and an interluekin-1 receptor antagonist [anakinra (ANA)]) were included. Of these, 12 were in allogeneic and one in autologous transplant. Insulin independence with decreased islet cells and number of transfusions were reported with their use. One infection was reported in a group receiving ETA. Analysis suggested that the use of ETA ± ANA have the potential to improve outcomes in islet cell transplant.     

Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra

Familial Mediterranean fever is an autosomal-recessive autoinflammatory disorder more commonly observed in Mediterranean populations and characterized by recurrent episodes of fever, serositis, myalgia and arthritis. There is rarely any association with spondyloarthritis. The most important long-term complication is progressive systemic type AA amyloidosis. Treatment with colchicine is effective in reducing the frequency of attacks and prevents the development of amyloidosis. However, 5% of cases are considered resistant to colchicine. We here describe the case of a 39-year-old man, with a history of arthritis, arthralgias, and sacroiliitis in the course of a familial Mediterranean fever. He is homozygous for the M694I mutation in the MEFV gene. He subsequently developed myositis of the right quadriceps muscle confirmed by magnetic resonance imaging, electromyography and histology. He had frequent and severe arthralgias, despite colchicine, then etanercept and adalimumab, impairing his quality of life. The patient was successfully treated with the IL-1 receptor antagonist anakinra with a dramatic improvement of muscular and articular symptoms. To our knowledge, our patient is the first patient with coexisting FMF, spondyloarthritis and myositis responding to anakinra treatment. Moreover this is the second case in the literature of myositis associated with familial Mediterranean fever.