Rilonacept

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Compound Name:RilonaceptMolecular Target:IL-1 beta (IL-1?)Molecular Structure:Dimeric fusion protein; ligand-binding domains of IL-1 receptor (IL-1R) & IL-1 receptor accessory protein (IL-1RAcP) linked to human IgG1Licensed Indication:cryopyrin-associated periodic fever syndromes (CAPS), including Muckle-Wells syndrome (MWS) and familial cold autinflammatory syndrome (FCAS) in children 12 years and olderManufacturer and/or Distributor:RegeneronInitial FDA Approval:2008Summary:Rilonacept (Arcalyst) is a genetically engineered homodimeric fusion protein consisting of the ligand-binding domains of the IL-1 receptor (IL-1R) and the IL-1 receptor accessory protein (IL-1RAcP) linked to the Fc portion of human IgG1 (MW ~251 kDa). Rilonacept binds to IL-1b, and thereby blocks its interaction with the cell bound IL-1R. It also binds to IL-1a and the IL-1 receptor antagonist (IL-1ra). Rilonacept is the first approved biologic in the new class of therapeutics known as 'Cytokine Traps'. These 'traps' are engineered to exhibit much higher binding avidities to their targets than traditional decoy receptor. Rilonacept is generally administered as a weekly subcutaneous 160 mg maintenance dose for adults older than 18 years of age. The loading dose is given at two separate injections sites (each injection is 160 mg) on the same day for a total of 320 mg dose. For pediatric dosing (ages 12-18), the maintenance dose is 2.2 mg/kg weekly. Rilonacept received FDA approval in 2008 under Orphan Drug Status for treatment of cryopyrin-associated periodic fever syndromes (CAPS), including Muckle-Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS) in children 12 years and older. These rare autosomal dominant conditions are caused by mutations in the gene (NLRP-3) coding for the inflammasome protein cryopyrin, which regulates the activation of IL-1b by caspase-1. This proinflammatory cytokine also has been implicated in the pathogenesis of gout, and its inhibition has now been evaluated in several clinical trials for flare prophylaxis. The FDA Advisory Panel voted against the approval of rilonacept for the treatment of gout in May 2012. Rilonacept has also been studied in the treatment of subacromial bursititis against triamcinolone acetonide injections and was less effacious in a small unblinded study of 33 subjects. Safety concerns with rilonacept include infections and hypersensitivity reactions. Treated patients should not receive live vaccines. Taking rilonacept with TNF inhibitors is not recommended because this may increase the risk of serious infections. The most commonly reported adverse reactions associated with rilonacept were injection site reaction and upper respiratory tract infection. Patients should be monitored for changes in their lipid profiles while on this medication.References

Package Insert: https://www.regeneron.com/sites/default/files/Arcalyst_FPI.pdf

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3. Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008 Aug;58(8):2443-2452. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18668535

4. Hoffman HM. Rilonacept for the treatment of cryopyrin-associated periodic syndromes (CAPS). Expert Opin Biol Ther. 2009 Apr;9(4):519-531. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19344287

5. Kastner DL, Aksentijevich I, Goldbach-Mansky R. Autoinflammatory disease reloaded: a clinical perspective. Cell. 2010 Mar 19;140(6):784-790. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20303869

6. Sivera F, Wechalekar MD, Andrés M, Buchbinder R, Carmona L. Interleukin-1 inhibitors for acute gout. Cochrane Database Syst Rev. 2014 Sep 1;9:CD009993. http://www.ncbi.nlm.nih.gov/pubmed/25177840

7. Cavalli G, Dinarello CA. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford). 2015 Dec;54(12):2134-44. http://www.ncbi.nlm.nih.gov/pubmed/26209330

8. Carroll MB, Motley SA, Wohlford S, Ramsey BC. Rilonacept in the treatment of subacromial bursitis: A randomized, non-inferiority, unblinded study versus triamcinolone acetonide. Joint Bone Spine. 2015 Dec;82(6):446-50. doi: 10.1016/j.jbspin.2015.02.009. Epub 2015 Jul 13. https://www.ncbi.nlm.nih.gov/pubmed/26184525

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