Identification
- Summary
Rilonacept is an IL-1 inhibitor used to treat cryopyrin-associated periodic syndrome, a rare hereditary inflammatory disorder.
- Brand Names
- Arcalyst
- Generic Name
- Rilonacept
- DrugBank Accession Number
- DB06372
- Background
Rilonacept is a dimeric fusion protein consisting of portions of IL-1R and the IL-1R accessory protein linked to the Fc portion of immunoglobulin G1. Rilonacept functions as an interleukin 1 inhibitor and is used in the treatment of CAPS, also known as cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children greater than 12 years old.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Chemical Formula
- C9030H13932N2400O2670S74
- Protein Average Weight
- 251000.0 Da
- Sequences
>8750_M|rilonacept|Homo sapiens||FUSION-IL1RAP-IL1R1-GAMMA-1 (IL1RAP+(Pr21-359)(1-339)+IL1R1+(Pr22-333)(340-651)+HINGE-REGION(652-663)+CH2(664-773)+CH3(774-880))|||||||880||||MW 100630.6|MW 100630.6| SERCDDWGLDTMRQIQVFEDEPARIKCPLFEHFLKFNYSTAHSAGLTLIWYWTRQDRDLE EPINFRLPENRISKEKDVLWFRPTLLNDTGNYTCMLRNTTYCSKVAFPLEVVQKDSCFNS PMKLPVHKLYIEYGIQRITCPNVDGYFPSSVKPTITWYMGCYKIQNFNNVIPEGMNLSFL IALISNNGNYTCVVTYPENGRTFHLTRTLTVKVVGSPKNAVPPVIHSPNDHVVYEKEPGE ELLIPCTVYFSFLMDSRNEVWWTIDGKKPDDITIDVTINESISHSRTEDETRTQILSIKK VTSEDLKRSYVCHARSAKGEVAKAAKVKQKVPAPRYTVEKCKEREEKIILVSSANEIDVR PCPLNPNEHKGTITWYKDDSKTPVSTEQASRIHQHKEKLWFVPAKVEDSGHYYCVVRNSS YCLRIKISAKFVENEPNLCYNAQAIFKQKLPVAGDGGLVCPYMEFFKNENNELPKLQWYK DCKPLLLDNIHFSGVKDRLIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEENK PTRPVIVSPANETMEVDLGSQIQLICNVTGQLSDIAYWKWNGSVIDEDDPVLGEDYYSVE NPANKRRSTLITVLNISEIESRFYKHPFTCFAKNTHGIDAAYIQLIYPVTNSGDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format- Synonyms
- interleukin-1 (IL-1) trap
- Rilonacept
Pharmacology
- Indication
Rilonacept is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in patients aged 12 and older. Rilonacept is also indicated for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adult and pediatric patients weighing at least 10 kg. Finally, rilonacept is indicated for the treatment of recurrent pericarditis (RP) and to reduce the risk of RP recurrence in patients aged 12 and older.5
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Treatment with Rilonacept resulted in decreased levels of mean C-Reactive Protein (CRP) and Serum Amyloid A (SAA). Higher levels of CRP and SAA are associated with inflammatory disease activity found in patients with Cryopyrin-Associated Periodic Syndromes.
- Mechanism of action
CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto-inflammatory Syndtrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis are features common to all disorders. In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) with reduced affinity. By binding IL-1, rilonacept prevents the activation of IL-1 receptors, thus reducing inflammatory responses and other effects related to an excess of IL-1.
Target Actions Organism UInterleukin-1 beta binderHumans UInterleukin-1 alpha binderHumans UInterleukin-1 receptor antagonist protein binderHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
8.6 days
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Rilonacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Rilonacept. Abrocitinib The metabolism of Abrocitinib can be increased when combined with Rilonacept. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Rilonacept. Acebutolol The metabolism of Acebutolol can be increased when combined with Rilonacept. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Rilonacept. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Rilonacept. Acetohexamide The metabolism of Acetohexamide can be increased when combined with Rilonacept. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be increased when combined with Rilonacept. Acyclovir The metabolism of Acyclovir can be increased when combined with Rilonacept. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Arcalyst Injection, powder, lyophilized, for solution 160 mg/2mL Subcutaneous Regeneron Pharmaceuticals, Inc. 2008-02-27 2022-01-31 US 
Arcalyst Injection, powder, lyophilized, for solution 160 mg/2mL Subcutaneous Kiniksa Pharmaceuticals (Uk), Ltd. 2008-02-27 Not applicable US Rilonacept Regeneron Injection, powder, for solution 80 mg/ml Subcutaneous Regeneron Pharmaceuticals 2016-09-07 2012-10-30 EU 
Categories
- ATC Codes
- L04AC04 — Rilonacept
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Anti-Inflammatory Agents
- Antineoplastic and Immunomodulating Agents
- Immunosuppressive Agents
- Immunotherapy
- Interleukin Inhibitors
- Interleukin-1 Blockers
- Interleukin-1 Receptor Accessory Protein
- Proteins
- Receptors, Interleukin-1 Type I
- Recombinant Proteins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8K80YB5GMG
- CAS number
- 501081-76-1
References
- Synthesis Reference
Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells.
- General References
- Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, Weinstein SP: Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012 Oct;34(10):2091-103. doi: 10.1016/j.clinthera.2012.09.009. Epub 2012 Sep 29. [Article]
- Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
- Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. [Article]
- Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
- FDA Approved Drug Products: ARCALYST (rilonacept) for subcutaneous injection [Link]
- External Links
- KEGG Drug
- D06635
- PubChem Substance
- 347910349
- 763450
- ChEMBL
- CHEMBL1201830
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Rilonacept
- FDA label
- Download (148 KB)
- MSDS
- Download (568 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Prevention Renal Insufficiency,Chronic 1 3 Completed Prevention Gouty Arthritis 1 3 Completed Treatment Acute Gout Flare 1 3 Completed Treatment Familial Cold Autoinflammatory Syndrome (FCAS) / Genetic Diseases, Inborn / Muckle-Wells Syndrome (MWS) 1 3 Completed Treatment Gouty Arthritis 1 3 Completed Treatment Intercritical Gout 1 3 Completed Treatment Recurrent Pericarditis 1 3 Terminated Treatment Gouty Arthritis 1 2 Completed Treatment Alcoholic Hepatitis (AH) 1 2 Completed Treatment Atherosclerosis / Coronary Artery Disease (CAD) / Endothelial Dysfunction / Inflammation 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Subcutaneous 160 mg/2mL Injection, powder, for solution Subcutaneous 80 mg/ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5844099 No 1998-12-01 2020-01-01 US US8114394 No 2012-02-14 2020-01-01 US US8080248 No 2011-12-20 2020-01-01 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Protein domain specific binding
- Specific Function
- Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
- Gene Name
- IL1B
- Uniprot ID
- P01584
- Uniprot Name
- Interleukin-1 beta
- Molecular Weight
- 30747.7 Da
References
- Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
- Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Cytokine activity
- Specific Function
- Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are in...
- Gene Name
- IL1A
- Uniprot ID
- P01583
- Uniprot Name
- Interleukin-1 alpha
- Molecular Weight
- 30606.29 Da
References
- Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
- Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Interleukin-1, type ii receptor binding
- Specific Function
- Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional int...
- Gene Name
- IL1RN
- Uniprot ID
- P18510
- Uniprot Name
- Interleukin-1 receptor antagonist protein
- Molecular Weight
- 20054.82 Da
References
- Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. [Article]
- Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
Drug created at March 19, 2008 16:27 / Updated at February 18, 2022 00:37