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PhA60104 Drug Discovery & Development
- 1. PHA60104 DRUG DISCOVERY & DEVELOPMENT USTEKINUMAB Treatments for Management of Psoriasis
- 2. Group members Chia Kay Veng 0315349 Liew Lee Bing 0321961 Muhammad Haris Ursilaniew 0325909 Sathiavani A/P Arishkrinan 0316271 Tan Kian Leong 0323426
- 3. Introduction Known as Stelara and CNTO 1275 Plaque psoriasis and psoriatic arthritis p40 interleukin-12 (IL-12) and interleukin-23 (IL-23) subunit Functions : - inhibition of IL-12 and IL-23- mediated signalling - downstream cytokine production - inhibition of cellular activation Usually given as syringe and vial Crucial to be given according to a fixed schedule.
- 4. Properties of Protein Target IL-12 also known as the cytotoxic lymphocyte maturation factor (CLMF) or natural killer stimulatory factor (NSFK) is a disulphide- linked heterodimeric (p40+p35) cytokine. IL-12 are produced by monocytes, macrophages and dendritic cells when pathogens interact with the T- cells (Ebioscience.com 2016) IL-23 is also a disulphide-linked heterodimer (p40+p19) secreted by activated dendritic cells and macrophages (Ebioscience.com 2016).
- 5. Mode of Mechanism Binds specifically to IL-12 (Interleukin 12) and IL-23 (Interleukin 23) which are responsible in the inflammatory and immune responses, such as activation of NK (natural killer) cells and T-cell + CD4 activation and differentiation (RxList 2016). Interaction between IL-12 and IL-23 with IL-12R硫1, a cell-surface receptor chain, was disrupted therefore mechanism that are mediated by these 2 interleukins were disrupted.ustekinumab directed against naturally occurring proteins interleukin 12 and interleukin 23, that regulate the immune system and immune mediated disorders (Reddy et al. 2007). Activation of proliferation in the cell, activation of IFN gamma and activate cell cytotoxicity can be done by these IL-12which contributes highly to the immune responses (Ebioscience.com 2016). The IL-23 regulates the Th17 function and cell proliferation which plays a role in the innate and adaptive immunity (Ebioscience.com 2016).
- 6. Development of Derivatives In 21st January 2015, Cosentyx (secukinumab) was approved to treat adults with moderate-to severe plaque psoriasis (U.S. Food & Drug Administration 2015). Secukinumab - An antibody which binds to a protein interleukin (IL) 17A (Langley et al. 2014). - Significantly improves patient-reported itching, pain and scaling in adults with moderate to severe psoriasis (Strober et al. 2016) - 44.3% : 24.4% of Cosentyx (secukinumab) : Stelara (ustekinumab) at week 16 reach completely clear skin (Hilton 2015). - Superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks (Tha巽i et al. 2015).
- 7. Side Effects Psoriatic arthritis, the common side effects are nausea and dental infections. Cold-like symptoms such as runny nose and sore throat. Fatigueness, diarrhea and skin rashes. Bruising, itching and swelling of the skin. Arthralgia Immunosuppression, or a weakened immune system. Increased risk of infections such as tuberculosis Serious effects include reverse posterior leukoencephalopathy syndrome (RPLS) (Cunha 2016)
- 8. Future Development Shows promising effects for immune-mediated inflammatory diseases (IMID) such as Crohns disease (Jnj 2016). Ustekinumab is also in the Phase II study to evaluate its efficacy in treating sarcoidosis.
- 9. Conclusion Not only effective but as well safe Further studies and researches - to expose the efficacy and side effect statues - comparison of both Consentyx and Stelara
- 10. ReferencesCunha, JP 2016, Sterela Side Effect Centre, Common Side Effects Of Stelara Injection (Ustekinumab) Drug Center - Rxlist., viewed 17 November 2016, <http://www.rxlist.com/stelara-side-effects-drug-center.htm> Ebioscience.com. (2016). IL-12 Overview. [online] Available at: http://www.ebioscience.com/knowledge-center/antigen/il-12.htm [Accessed 24 Nov. 2016]. Dermatology Times. (2016). Secukinumab vs. Ustekinumab. [online] Available at: http://dermatologytimes.modernmedicine.com/dermatology- times/news/secukinumab-vs-ustekinumab?page=full [Accessed 24 Nov. 2016]. Jnj.com. 2016, FDA Approves STELARA速 (Ustekinumab) for Treatment of Adults With Moderately to Severely Active Crohns Disease | Johnson & Johnson, viewed 20 November 2016, <https://www.jnj.com/media-center/press-releases/fda- approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely- active-crohns-disease> Langley, R, Elewski, B, Lebwohl, M, Reich, K, Griffiths, C, Papp, K, Puig, L, Nakagawa, H, Spelman, L, Sigurgeirsson, B, Rivas, E, Tsai, T, Wasel, N, Tyring, S, Salko, T, Hampele, I, Notter, M, Karpov, A, Helou, S & Papavassilis, C 2014, 'Secukinumab in Plaque Psoriasis Results of Two Phase 3 Trials', New England Journal of Medicine, vol. 371, no. 4, pp. 326-338. PMG Research 2016, 'Plaque Psoriasis comparing secukinumab (Cosentyx速) with ustekinumab (Stelara速) Clinical Trial in Charlotte, NC', viewed 14 November 2016, <https://www.pmg-research.com/studies/facility/charlotte/plaque-psoriasis- comparing-secukinumab-cosentyx-with-ustekinumab-stelara/>. Psoriasis.org. (2016). Psoriasis types: Plaque Psoriasis | National Psoriasis Foundation. [online] Available at: https://www.psoriasis.org/about-psoriasis/types/plaque [Accessed 24 Nov. 2016]. Reddy, M, Davis, C, Wong, J, Marsters, P, Pendley, C & Prabhakar, U 2007, 'Modulation of CLA, IL-12R, CD40L, and IL-2R留 expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275', Cellular Immunology, vol. 247, issue 1, pp. 1-11. RxList. 2016, Stelara Injection (Ustekinumab) Drug Information: Clinical Pharmacology - Prescribing Information at RxList., viewed 17 November 2016, <http://www.rxlist.com/stelara- drug/clinical-pharmacology.htm> Strober, B, Sigurgeirsson, B, Popp, G, Sinclair, R, Krell, J, Stonkus, S, Septe, M, Elewski, B, Gottlieb, A, Zhao, Y, Tran, M, Karpov, A, McLeod, L, Mordin, M, Papavassilis, C, Nyirady, J & Lebwohl, M 2016, 'Secukinumab improves patient-reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo-controlled clinical trials', International Journal of Dermatology, vol. 55, no. 4, pp. 401-407. Tha巽i, D, Blauvelt, A, Reich, K, Tsai, T, Vanaclocha, F, Kingo, K, Ziv, M, Pinter, A, Hugot, S, You, R & Milutinovic, M 2015, 'Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial', Journal of the American Academy of Dermatology, vol. 73, no. 3, pp. 400-409. U.S. Food & Drug Administration 2015, FDA approves new psoriasis drug Cosentyx, viewed 16 November 2016, <http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430969.htm>.
Editor's Notes
- #7: Secukinumab is an antibody which binds to a protein interleukin (IL) 17A (Langley et al. 2014) which is involved in inflammation, where different with ustekinumab that targeting interleukin 12 and interleukin 23.