Off-label use of canakinumab in pediatric rheumatology and rare diseases

Giudice, Emanuela Del; Sota, Jurgen; Orlando, Francesca; Picciano, Ludovica; Cimaz, Rolando; Cantarini, Luca; Mauro, Angela

doi:10.3389/fmed.2022.998281

Cited by 9 publications

(6 citation statements)

References 70 publications

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“…The administration of high doses of corticosteroids is considered the initial treatment. If not effective, adjunctive therapy with immunomodulatory and biological agents, such as infliximab, anakinra, or cyclosporine, can be considered (24)(25)(26). In the present study, both patients received high-dose intravenous methylprednisolone pulse therapy with improvement.…”

Section: Discussionmentioning

confidence: 99%

Kawasaki disease complicated with shock syndrome, macrophage activation syndrome, and acute abdomen in children: Two case reports

She

Chen

2023

Front. Pediatr.

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BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can involve multiple organs. Few reports have been published about KD patients presenting with multiple complications such as acute abdomen, KD shock syndrome (KDSS), and macrophage activation syndrome (MAS).Case DescriptionWe present the cases of two males (9 and 12 years old) diagnosed with KD accompanied by rare manifestations. Case 1 is a 9-year-old male treated for acute appendicitis, KDSS, and MAS. Case 2 is a 12-year-old male who presented with KDSS, MAS, and an ileal perforation. They were treated with intravenous immunoglobulin, aspirin, high-dose corticosteroids, vasoactive drugs, and symptomatic treatment, with good outcomes.ConclusionsClinicians should be aware of the possibility of KD in the presence of fever and unusual manifestations, such as severe inflammatory indicators and acute abdomen that is nonresponsive to antibiotic therapy. Meanwhile, KD-related unusual complications should be recognized, such as KDSS and MAS.

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Section: Discussionmentioning

confidence: 99%

Kawasaki disease complicated with shock syndrome, macrophage activation syndrome, and acute abdomen in children: Two case reports

She

Chen

2023

Front. Pediatr.

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“…We used inclusion criteria for these groups, similar to what was published earlier ( 9 ). Canakinumab showed efficacy in AIDs in an earlier study, where it was administered off-label ( 64 ). It was successfully prescribed in several distinct AIDs, including DIRA, Majeed syndrome, PAPA syndrome, DADA2, Blau syndrome, systemic juvenile idiopathic arthritis (sJIA), MAS, and fibrodysplasia ossificans progressiva ( 65 – 74 ).…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study

Alexeeva,

Shingarova,

Dvoryakovskaya

et al. 2023

Front. Med.

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IntroductionThe blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.MethodsInformation on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.ResultsThe median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: IL10, NLRP12, STAT2, C8B, LPIN2, NLRC4, PSMB8, PRF1, CARD14, IFIH1, LYST, NFAT5, PLCG2, COPA, IL23R, STXBP2, IL36RN, JAK1, DDX58, LACC1, LRBA, TNFRSF11A, PTHR1, STAT4, TNFRSF1B, TNFAIP3, TREX1, and SLC7A7. The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab (n = 4) and sarilumab (n = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.ConclusionThe treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.

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“…Both anakinra, a recombinant human IL-1Ra, and rilonacept, a recombinant fusion protein that binds to both IL-1β and IL-1apha, are recommended first-line agents for DIRA (74,75). IL-1β antagonist canakinumab does not appear as consistently efficacious as these agents, possibly due to ongoing IL-1α activity in these patients (60,75,76). Similarly, Majeed Syndrome appears to response well to anti-IL-1 activity, with reports of efficacy with anakinra and canakinumab (77,78).…”

Section: Management Of Autoinflammatory Bone Diseasesmentioning

confidence: 99%

Pediatric autoinflammatory bone disorders—a mini review with special focus on pathogenesis and inborn errors of immunity

Hetrick

Oliver

2023

Front. Pediatr.

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Autoinflammatory bone disorders are a group of diseases characterized by sterile osteomyelitis. This includes chronic nonbacterial osteomyelitis and the monogenic forms, Majeed syndrome and deficiency of the interleukin-1 receptor antagonist. These disorders result from innate immune system dysregulation and cytokine imbalance that triggers inflammasome activation causing downstream osteoclastogenesis and excessive bone remodeling. In this review, we will summarize the immunopathogenesis of pediatric autoinflammatory bone diseases with a special focus on the genetics and inborn errors of immunity, while briefly touching on the clinical manifestations and management of each disease as well as areas for future research.

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Off-label use of canakinumab in pediatric rheumatology and rare diseases

Cited by 9 publications

References 70 publications

Kawasaki disease complicated with shock syndrome, macrophage activation syndrome, and acute abdomen in children: Two case reports

Kawasaki disease complicated with shock syndrome, macrophage activation syndrome, and acute abdomen in children: Two case reports

Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study

Pediatric autoinflammatory bone disorders—a mini review with special focus on pathogenesis and inborn errors of immunity

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