Introduction
Using the articles from the annotated bibliography, we were required to compose a literature review that synthesized all these articles. We had to take the common trend between all the articles and report on them in an organized method. I chose to use a chronology because that best suited the articles I chose.
Peer Review and Instructor Feedback
This is an in class exercise we did to improve our understanding of in-text CSE citations and how to write a literature review
Final Draft
A Historical Development of Secukinumab as a Treatment for Plaque Psoriasis
Abstract
Secukinumab is a monoclonal antibody treatment used for plaque psoriasis. It targets the interleukin-17A (IL-17A) protein that is responsible for inflammation throughout the body (Hueber et al. 2010). Secukinumab was initially created in Novartis laboratories (Hueber et al. 2010) and went through many phase trials to become FDA approved (Langley et al. 2014). Eventually, it was confirmed to be the most effective and safe monoclonal antibody available to be used for plaque psoriasis, both long and short-term (Thaçi et al. 2015; Bissonnette et al. 2018). Its development can be used as a guide for creating future monoclonal antibodies that may treat or cure currently incurable illnesses.
Introduction
Plaque psoriasis is an autoimmune, dermatological condition that is characterized by dry, itchy plaques across the body. The plaques develop when skin cells continuously regenerate, which causes them to layer on top of each other. These plaques cause severe deterioration in patients’ quality of life, both physically and mentally (Langley et al. 2014). Psoriasis is an inflammatory disease that is primarily controlled by a protein called interleukin-17A (1L-17A) (Langley et al. 2014). The treatment developed after discovering IL-17A was responsible for causing psoriasis was called AIN457 or secukinumab (Hueber et al. 2010). Secukinumab is a monoclonal antibody, which is a type of medication that is used to block specific types of cells in the body. Monoclonal antibodies are still a new type of medication, but secukinumab’s history shows that not only has it been successfully approved by the FDA, but it also is a viable treatment option. Secukinumab’s development demonstrates the progress being made in monoclonal antibody research, and how similar developments can be applied to other incurable diseases.
Initial Development
Hueber et al. (2010) is part of a pharmacological company based in Switzerland named Novartis, which created AIN457 as a monoclonal antibody for IL-17A. IL-17A is responsible for causing inflammatory diseases such as collagen-induced arthritis and autoimmune uveitis in animals. However, to determine if this same protein was responsible for causing similar inflammatory diseases in humans, AIN457 was tested on individuals with inflammatory diseases. A study was conducted with patients diagnosed with plaque psoriasis, noninfectious uveitis, and rheumatoid arthritis (RA). For the psoriasis portion of the study, 36 patients with plaque psoriasis were split into two groups. One group received a 3 mg/kg dosage of AIN457 while the other group received a placebo. After 12 weeks, approximately 75% of patients who received the AIN457 treatment showed a significant increase in clearer skin compared to the placebo group. Similar tests were conducted on individuals with rheumatoid arthritis and uveitis, and patients experienced positive results. These results signify that IL-17A plays a role in the pathogenesis of plaque psoriasis, which means that AIN457, now called secukinumab, is a potential treatment option for plaque psoriasis.
Further Research: Phase III
Once IL-17A was determined to be part of the pathogenesis of psoriasis (Hueber et al. 2010), phase trials for secukinumab commenced (Langley et al. 2014). Phase trials are a series of clinical studies used to test new drugs. Phase III of a study evaluates the efficacy and safety of a drug on a large group of the target population (Langley et al. 2014). For secukinumab, phase III consisted of a large dosage test (300 mg of secukinumab), a smaller dosage (150 mg of secukinumab), an etanercept (an injection used to treat psoriasis), and a placebo. Over a 52-week period, both dosages of secukinumab resulted in patients with clearer skin over both the etanercept and the placebo (Langley et al. 2014). The Psoriasis Area and Severity Index (PASI) is a measure of skin clearance for patients with plaque psoriasis. PASI 75 means a patient has 75% fewer plaques on their skin than originally measured, and it is a standard benchmark for considering a patient to have significantly clearer skin (Hueber et al. 2010). An average of 75% of individuals tested with secukinumab achieved PASI 75 (Langley et al. 2014), which was similar to the developmental study that also achieved 75% of patients with PASI 75 (Hueber et al. 2010). The small sample size of the experimental group while secukinumab was being first developed limited the extrapolation of the data (Hueber et al. 2010). It could not be properly applied to the general population, but a phase III trial on nearly 2000 patients confirm that secukinumab is effective at reducing the plaques and IL-17A is the correct protein to target for plaque psoriasis treatment with monoclonal antibodies (Hueber et al. 2010; Langley et al. 2014). This was what allowed secukinumab to be FDA approved in 2015.
Efficacy Compared to Other Medications
Once secukinumab was confirmed as an effective treatment for increasing skin clearance in plaque psoriasis and an effective blocker of IL-17A, its efficacy compared to other anti-inflammatory monoclonal antibodies was to be to be tested (Langley et al. 2014; Thaçi et al. 2015). The phase III trial demonstrated secukinumab as a superior treatment to etanercept; however, this was only the beginning of comparison treatments (Langley et al. 2014; Thaçi et al. 2015). Head-to-head results comparing the efficacy of medications that treat plaque psoriasis are necessary to inform physicians and patients of the best available treatment options (Thaçi et al. 2015). Ustekinumab is a monoclonal antibody that targets IL-12 and IL-23, which similarly act as inflammatory agents (Thaçi et al. 2015). Instead of using PASI 75 as the benchmark for patient skin clearance, PASI 90 was used. This increased standard meant that both medications could provide accurate PASI 75 results, but PASI 90 would show which of the two is able to produce even more skin clearance (Thaçi et al. 2015), which shows how carefully designed and specific secukinumab trials have become since the initial trials (Hueber et al. 2010). 676 patients were split evenly into two groups, where each received standard dosages of either secukinumab or ustekinumab. After 16 weeks, 79% of the secukinumab group achieved PASI 90, whereas only 57.6% of the ustekinumab group achieved PASI 90 (Thaçi et al. 2015). Not only is the efficacy of secukinumab is consistently validated throughout every trial that uses it a variable, but also its superiority to other plaque psoriasis medications (etanercepts and ustekinumab) have been confirmed as well (Langley et al. 2014; Thaçi et al. 2015).
Longevity
Psoriasis is a lifelong disease that requires life-long management (Bissonnette et al. 2018). Until this point, studies surrounding secukinumab have only lasted for a maximum of one year (Langley et al. 2014). Knowing that secukinumab is the most effective and safe treatment option available (Langley et al. 2014; Thaçi et al. 2015), the question now becomes is it sustainable long-term (Bissonnette et al. 2018)? In a 126-patient pool that received a 300 mg dosage of secukinumab every 4 weeks for 5 years, the average result was PASI 90. By year 5, 88.5% of patients achieved PASI 75, 66.4% of patients achieved PASI 90, and 41% achieved PASI 100 (Bissonnette et al. 2018). Throughout five years, the effectiveness of secukinumab and its safety remained valid, which provides the most updated status of the efficacy of the medication as a long-term treatment (Langley et al. 2014; Thaçi et al. 2015; Bissonnette et al. 2018).
Conclusion
Bissonnette et al. (2018) was able to confirm secukinumab’s efficacy as a monoclonal antibody treatment for plaque psoriasis. That study, along with the others conducted before it, are fundamental to physicians for deciding what medication to offer plaque psoriasis patients. Also, after observing the path that secukinumab has taken to become a potent treatment for plaque psoriasis, it is possible that other monoclonal antibodies can be created in a similar fashion. Once the cell or specific protein that potentially causes a disease is found, a monoclonal antibody can be created to block that cell from doing any further damage. Soon, incurable diseases will have potent monoclonal antibody treatments once their root causes are found.
References
Bissonnette R, Luger T, Thaçi D, Toth D, Lacombe A, Xia S, Mazur R, Patekar M, Charef P, Milutinovic M. 2018. Secukinumab demonstrates high sustained efficacy and a favourable safety profile in patients with moderate-to-severe psoriasis through 5 years of treatment (SCULPTURE extension study). J. Eur. Acad. Dermatol. Venereol. [accessed 2018 Apr 23]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.14878
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P. 2010. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci. Transl. Med. [accessed 2018 Apr 23];2(52). Available from: http://stm.sciencemag.org/content/2/52/52ra72.full
Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B. 2014. Secukinumab in plaque psoriasis — results of two phase 3 trials. N. Engl. J. Med. [accessed 2018 Apr 23];371(4):326–338. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1314258
Thaçi D, Blauvelt A, Reich K, Tsai T-F, Vanaclocha F, Kingo K, Ziv M, Pinter A, Hugot S, You R. 2015. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J. Am. Acad. Dermatol. [accessed 2018 Apr 23];73(3):400–409. Available from: https://www.sciencedirect.com/science/article/pii/S0190962215016837
Self Assessment
This assignment was the most unique one out of all the writings I did this semester. This literature review was a large synthesis of multiple original research papers. I found it very difficult to not provide my own analysis of the ideas presented. This allowed me to engage in multimodal composing across disciplinary contexts. I had never written a literature review before this, so to learn to write in a new style for the first time is always a challenge.
One thing I think I did well was taking the various information and data sets from the articles and connecting them with each other to create a single idea for my audience. By using multiple citations, which I have developed over the course of the semester, I was able to allow the texts to intermingle in a single sentence. Also, I think that my organization was effective in this assignment. By putting the articles in order of date, my readers can see the history of the research, and how the medication has developed over time. Finally, I practiced using library resources, mainly the databases, so that I could find my articles to use for the literature review.
One thing I did poorly was not formulating and articulating a stance in my writing. Although this assignment was not arguing a point, there was a still a thesis that needed to be discussed. I think my thesis statement was weak and did not resonate well with my readers.
One thing I want to improve is my conclusion. I think that I connected the broader theme of my literature review with the health issues today, but it could have been written better so that the ideas were better embedded in the text.
Farhan's Writing for the Sciences Portfolio 