A decade of anti-IL-1 therapy in CAPS - a spectrum of efficacy in this spectrum of diseases

Lane, Thirusha; Williams, Ruth; Rowczenio, DM; Youngstein, Taryn; Trojer, H; Pepper, RJ; Brogan, Paul A.; Hawkins, PN; Lachmann, HJ

doi:10.1186/1546-0096-13-s1-o65

Cited by 4 publications

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“…Ten observational studies reported the effectiveness of canakinumab in patients with different CAPS phenotypes and of various age groups. 34 39– 41 48 52 59 66 82 92 Among the studies reporting CR/PR, 93% of canakinumab-treated MWS patients achieved a CR at short-term follow-up. 59 Patients who achieved a CR with canakinumab ranged from 62% 48 to 93% 59 at mid-term follow-up, and 50% 34 52 to 100% 82 at long-term follow-up (online supplementary figure 2A–B).…”

Section: Resultsmentioning

confidence: 99%

“…In CAPS studies, patients were switched from anakinra to canakinumab in 9 of the 11 studies, 34 36 38 45 57 59 65 67 86 and from canakinumab to anakinra in three studies. 39 41 45 The most common reasons patients switched from anakinra to canakinumab were insufficient response, inconvenience of daily injections, local reactions to anakinra and patient/parent preference (table 4). In three studies in which patients switched from canakinumab to anakinra, the main reasons included inadequate response, 45 and AE.…”

Section: Resultsmentioning

confidence: 99%

“…In three studies in which patients switched from canakinumab to anakinra, the main reasons included inadequate response, 45 and AE. 41 One patient was initially treated with canakinumab but changed to anakinra during pregnancy, and then restarted canakinumab following a successful pregnancy. 45…”

Section: Resultsmentioning

confidence: 99%

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Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome

et al. 2020

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ObjectivesSeveral therapies are used for the treatment of rareautoinflammatory conditions like cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome (HIDS)/mevalonate kinase deficiency (MKD) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS). However, reviews reporting on treatment outcomes of these therapies are lacking.MethodsA systematic literature review was conducted using Embase, MEDLINE, MEDLINE-In Process and Cochrane databases to identify the randomised/non-randomised controlled trials (RCTs/non-RCTs) and real-world observational studies of CAPS, HIDS/MKD and TRAPS published as full-texts (January 2000–September 2017) or conference abstracts (January 2014–September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded.ResultsOf the 3 342 retrieved publications, 72 studies were included (CAPS, n=43; HIDS/MKD, n=9; TRAPS, n=7; studies with ≥2 cohorts, n=13). Most studies were full-text (n=56), published after 2010 (n=56) and real-world observational studies (n=58). Among included studies, four were RCTs (canakinumab, n=2 (CAPS, n=1; HIDS/MKD and TRAPS, n=1); rilonacept, n=1 (in CAPS); simvastatin, n=1 (in HIDS/MKD)). Canakinumab and anakinra were the most commonly used therapies for CAPS and HIDS/MKD, whereas etanercept, canakinumab and anakinra were the most common for TRAPS. The available evidence suggested the efficacy or effectiveness of canakinumab and anakinra in CAPS, HIDS/MKD and TRAPS, and of etanercept in TRAPS; asingle RCT demonstrated the efficacy of rilonacept in CAPS.ConclusionsCanakinumab, anakinra, etanercept and rilonacept were reported to be well tolerated; however, injection-site reactions were observed frequently with anakinra, rilonacept and etanercept. Data on the use of tocilizumab, infliximab and adalimumab in these conditions were limited; thus, further research is warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome

et al. 2020

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“…Etanercept was stopped, and canakinumab and then anakinra (interleukin-1 [IL-1] antagonists) were trialled for eight months, unfortunately resulting in a recrudescence of knee and systemic inflammation. At that time the case was presented to a meeting as s an example of CAPS with a poor response to IL-1 therapy [ 2 ]. Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor (IL-6R) antagonist, was prescribed for three years, and joint effusion improved, CRP was suppressed, and the patient gained weight.…”

Section: Case Presentationmentioning

confidence: 99%

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function

Doctor,

Dudreuilh,

Perera

et al. 2024

JCM

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Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a young man with allograft dysfunction who had GTIN upon biopsy. We performed a thorough case review based on recovered records from early childhood and reassessed genetic testing results. We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type NOD2 and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). This suppressed his inflammatory disease and stabilised kidney function. We performed a literature review related to the emerging role of IL-6 pathway blockade in kidney transplantation. We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials.

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“…Interleukin (IL) 3 -1␣ and IL-1␤ are initiators and regulators of innate and acquired immunity (1,2), sterile inflammation, tissue remodeling (3), cell death (4), hypoxia-ischemia (5), and organ failure (6). First separately identified in 1974 (7), IL-1␣ and IL-1␤ signaling has since been implicated in a wide range of pathological conditions, including gout and rheumatoid arthritis (RA) (8), type II diabetes (9), and systemic autoinflammatory conditions such as cryopyrin-associated periodic syndromes (10), heart disease (11), and cancer (1).…”

mentioning

confidence: 99%

PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis

et al. 2019

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Interleukin-1 (IL-1) is a key mediator of inflammation and immunity. Naturally-occurring IL-1 receptor antagonist (IL-1Ra) binds and blocks the IL-1 receptor-1 (IL-1R1), preventing signaling. Anakinra, a recombinant form of IL-1Ra, is used to treat a spectrum of inflammatory diseases. However, anakinra is rapidly cleared from the body and requires daily administration. To create a longer-lasting alternative, PASylated IL-1Ra (PAS–IL-1Ra) has been generated by in-frame fusion of a long, defined-length, N-terminal Pro/Ala/Ser (PAS) random-coil polypeptide with IL-1Ra. Here, we compared the efficacy of two PAS–IL-1Ra molecules, PAS600–IL-1Ra and PAS800–IL-1Ra (carrying 600 and 800 PAS residues, respectively), with that of anakinra in mice. PAS600–IL-1Ra displayed markedly extended blood plasma levels 3 days post-administration, whereas anakinra was undetectable after 24 h. We also studied PAS600–IL-1Ra and PAS800–IL-1Ra for efficacy in monosodium urate (MSU) crystal-induced peritonitis. 5 days post-administration, PAS800–IL-1Ra significantly reduced leukocyte influx and inflammatory markers in MSU-induced peritonitis, whereas equimolar anakinra administered 24 h before MSU challenge was ineffective. The 6-h pretreatment with equimolar anakinra or PAS800–IL-1Ra before MSU challenge similarly reduced inflammatory markers. In cultured A549 lung carcinoma cells, anakinra, PAS600–IL-1Ra, and PAS800-IL-Ra reduced IL-1α–induced IL-6 and IL-8 levels with comparable potency. In human peripheral blood mononuclear cells, these molecules suppressed Candida albicans–induced production of the cancer-promoting cytokine IL-22. Surface plasmon resonance analyses revealed significant binding between PAS–IL-1Ra and IL-1R1, although with a slightly lower affinity than anakinra. These results validate PAS–IL-1Ra as an active IL-1 antagonist with marked in vivo potency and a significantly extended half-life compared with anakinra.

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A decade of anti-IL-1 therapy in CAPS - a spectrum of efficacy in this spectrum of diseases

Cited by 4 publications

References 0 publications

Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome

Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome

Granulomatous Tubulointerstitial Nephritis in a Kidney Allograft: Treatment with Interleukin-6 Receptor Antagonist Stabilises Kidney Function

PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis

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