Compound Name:SecukinumabMolecular Target:IL17AMolecular Structure:human immunoglobulin G1k (IgG1k) subclass monoclonal antibodyLicensed Indication:moderate to severe plaque psoriasis; ankylosing spondylitis; psoriatic arthritisManufacturer and/or Distributor:NovartisInitial FDA Approval2015SummarySecukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines. Secukinumab is specifically indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. It was used sucessfully to treat adult patients with ankylosing spondylitis and psoriatic arthritis when conventional treatments do not work well enough. Cosentyx is given by 300 mg subcutaneous injections as four weekly injections followed by monthly maintenance injections for 5 months. The FDA approval of Cosentyx on January 21, 2015 was based on four multicenter, randomized, double-blind, placebo-controlled studies involving 2,403 patients with psoriasis, 79% of those on Cosentyx achieved a 75% reduction in their Psoriasis Area and Severity Index (PASI) scores after 12 weeks of treatment. In addition, 65% of patients given Cosentyx had clear or nearly clear skin, compared with 27% of patients given etanercept and 2% of those given placebo. On September 30, Novartis announced the results from the pivotal Phase III FUTURE 1 study for secukinumab in psoriatic arthritis. In this study, secukinumab met the primary endpoint with a 20% reduction in the American College of Rheumatology response criteria (ACR 20) at week 24 showing rapid and significant clinical improvements versus placebo. In addition, secukinumab met all secondary endpoints, including improvements in skin and joint diseases and joint structural damage progression. Caution should be exercised when considering the use of Cosentyx in patients with a chronic infection or history of recurrent infection, and in patients with active Crohn’s disease. The most common side effects include diarrhea and upper respiratory infections with nasopharyngitis. Serious allergic reactions have been reported with the use of Cosentyx.References

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1. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014 Jul 24;371(4):326-38.

2. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015 Dec 24;373(26):2534-48.

3. Tzellos T, Kyrgidis A, Vakirlis E, Trigoni A. Secukinumab for ankylosing spondylitis. Lancet. 2014 Mar 1;383(9919):780.

4. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med. 2015 Oct;373(14):1329-39.

5. McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 Sep 19;386(9999):1137-46.

6. Burkett PR, Kuchroo VK. IL-17 Blockade in Psoriasis. Cell. 2016 Dec 15;167(7):1669.