Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States

Abstract

Background Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). Methods Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children (< 18 years) and adults and by subtype of PFS. Results Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). Conclusions This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Reasons for Initiating Canakinumab among Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still’s Disease in the U.S. Real-World Settings

“…Participating physicians included those who had prescribed canakinumab to ≥ 1 patient with Still’s disease from 2016 to 2018 and agreed to extract patient data in an online case report form (CRF). The methods are described in detail elsewhere [ 15 ].…”

Experience on the long‐term use of canakinumab in mevalonate kinase deficiency: A case series

“…in MKD is the basis for the use of canakinumab in this condition, with the aim of limiting all the IL-1β-related clinical manifestations. 2,6 Some authors suggested that an impaired prenylation of RhoA protein could be responsible for the IL-1β hypersecretion in MKD, through an increased activity of autoinflammatory pathways, as Rac1/PKB signaling and inflammasome-mediated routes. 8 Canakinumab was administered at a regular dosage (2 mg/kg every 4 weeks for patients <40 kg, 150 mg every 4 weeks for patients >40 kg).…”

“…2 Therefore, biological drugs are often needed to control inflammation after the failure of conventional treatments. 2 Anti-interleukin 1 (IL-1) drugs are approved for the treatment of PFS with a favorable safety and tolerability. 2,3 The 2021 EULAR/American College of Rheumatology recommendations state that in children with MKD, an anti-IL1 therapy is generally required.…”

“…2 Anti-interleukin 1 (IL-1) drugs are approved for the treatment of PFS with a favorable safety and tolerability. 2,3 The 2021 EULAR/American College of Rheumatology recommendations state that in children with MKD, an anti-IL1 therapy is generally required. [4][5][6] Two patients (1 and 3) were initially treated with anakinra.…”

“…Conventional treatments, such as oral steroids, non-steroidal antiinflammatory drugs, and methotrexate are usually the first choices of treatment, but they often provide just symptomatic relief. 2 Therefore, biological drugs are often needed to control inflammation after the failure of conventional treatments. 2 Anti-interleukin 1 (IL-1) drugs are approved for the treatment of PFS with a favorable safety and tolerability.…”