Anakinra: A Successful Anti-Inflammatory Rescue Medicine in Acute Onset Multisystem Inflammation

ABSTRACT

Aims Anakinra is an Interleukin-1 receptor (IL-1) antagonist;a biologic drug that has historically been used as part of longerterm management in methotrexate-resistant rheumatoid arthritis, cryopyrin-associated periodic syndromes and systemic juvenile idiopathic arthritis. We describe its successful use in acute multisystem inflammation in a cohort of recently treated children in a Tertiary Children's Hospital. Methods We reviewed the details of 6 acutely unwell inpatients admitted over the last 6 months, with acute multisystem inflammation, who had been treated with Anakinra as a rescue medication, following resistance to first-line anti-inflammatory medications. Five of these patients had been diagnosed with Paediatric Multisystem Inflammatory Syndrome temporarily associated with COVID-19 (PIMS). One of these patients had been diagnosed with Hemophagocytic Lymphohistiocytosis (HLH). Results The average length of initial treatment was 3.5 days before commencing Anakinra. All patients on Anakinra also received contemporaneous intravenous methylprednisolone treatment (IVMP), and 5/6 patients had received intravenous immunoglobulin therapy (IVIG). Common indications for commencing Anakinra were persisting fevers despite at least 3 days of IVMP, and increasing inflammatory markers despite first line treatment. The average C-reactive Protein (CRP) at initiation of Anakinra was 82 (range 32 to 132) and the average Ferritin at initiation was 1500 (range 129 to 4640), with the average treatment duration of 6.7 days until CRP normalised, and all with normal CRP two weeks after treatment. All patients were started on an initial 2mg/kg dose of Anakinra, rounded up to nearest 100mg dose in most. Five patients were prescribed a subcutaneous route whilst one patient was started on an IV route. Half of patients were commenced on a once daily regime, two patients were started on a twice daily regime, and one patient was started on a QDS regime. One patient required a dose increase due to ongoing fevers after initiation. Average treatment length for the patients diagnosed with PIMS was 8.6 days, whereas treatment length was 25 days in the patient with HLH. We also describe the need for inotropic support (1/5), significant echocardiography findings at presentation (3/5) and at 2 weeks post-discharge (1/5) in this cohort of patients with PIMS. Conclusion Anakinra was successfully used as an acute treatment for our 6 described patients with multisystem inflammation. With more recent waves of PIMS, Anakinra has increasingly been used as a second-line treatment. Its introduction ceased ongoing fevers in all patients;5 of 6 with immediate effect. There are some clear advantages of Anakinra as a rescue drug over other potential biological alternatives, namely;choice of preparation, tolerability and few described side effects with short-term use. We highlight the experiential effectiveness of the acute use of Anakinra in our cohort of children with hyperinflammation, and recommend its accessibility as an emergency drug.