Breakthroughs and Challenges: Psoriasis and treatment evolution

It is estimated that the worldwide prevalence of psoriasis is 3% of the population. It can affect anyone regardless of race, age, and geographical location. While genetic factors can contribute to the occurrence, many who do not have a family history of psoriasis can also be affected. Presentation can be mild to severe and can appear in different forms, ranging from pustular to joint involvement. During the ZPT Expo held on September 23, 2022, we were privileged to be able to witness a discussion on a breakthrough treatment for psoriasis – TALTZ® (Ixekizumab).

The event was graced by Dr. Bernardita I. Ortiz-Policarpio, FPDS and flawlessly moderated by Dr. Cecilia Roxas Rosete, FPDS, iFAAD, iFAADV, both renowned in the field of dermatology. 

Dr. Ortiz-Policarpio started her lecture by discussing the use of targeted therapy for cytokines that play a major role in the dysregulation of the innate and adaptive immune system. Much has been understood since it was first discovered in 2015, and we now know that there are different inflammatory pathways involved in the pathophysiology of psoriasis and how they can be specifically targeted to reduce symptoms.

Interleukin 17A

Ixekizumab is a monoclonal antibody that selectively targets interleukin-17A (IL-17A). ¹ IL-17A is a proinflammatory cytokine that is associated with psoriasis. IL-17A is known to combine with tumor necrosis factor-α to stimulate keratinocytes to produce mediators that would result in amplification loops that would contribute to self-perpetuating autocrine and paracrine reactions that mediate chronic inflammation, causing unrelenting symptoms. ² Targeting IL-17A thus halts the chronic inflammation seen in psoriasis and reduces neutrophils in the epidermis of skin lesions. ³

Dr. Ortiz-Policarpio then proceeded to discuss her patient who was put on the treatment and how they progressed from years of severe plaque psoriasis to complete clearance of symptoms in a span of just 1 month. According to her, many patients would come to dermatologists expecting a quick cure that could improve symptoms overnight, many frustrated with their quality of life. In a large-scale survey done by Baker CS, et. al. among Australian adults with psoriasis, quality of life of patients with different diseases were assessed using a questionnaire and the 5-dimension European quality of life instrument (EQ-5D). It was seen that patients with psoriasis had comparable EQ-5D Quality of Life scores to patients with chronic congestive heart failure or stable advanced gastric cancer and much lower scores than patients with early human immunodeficiency virus-1 infection or sub-syndromal bipolar depression. ⁴ Therefore, she called on her fellow colleagues to be more passionately aggressive in treating patients with psoriasis.

Evolution of treatment goals

Treatment goals of psoriasis have evolved over time, in 2004, achieving a Psoriasis Area Severity Index (PASI) 50 score was clinically meaningful and PASI 25 was recognized as minimal response to therapy. Eventually tumor necrosis factor (TNF) blocking therapies became available between the year 2004 - 2008 and the objective of treatment became PASI 75. More recently however, from the year 2015, with research work continuing to advance and newer biologics becoming available, dermatologists can safely aim for PASI 90 and PASI 100. ⁵˒⁶˒⁷˒⁸ 

According to several clinical trials conducted using Ixekizumab, more patients are now allowed to achieve complete or near-complete resolution. In the UNCOVER-2 study, the proportions of patients treated with Ixekizumab 80 mg every other week who achieved PASI 75, 90 and 100 responses at Week 12 were 90%, 71% and 41%, respectively. In the UNCOVER-3 study, the corresponding values were 87%, 68% and 38%, respectively. ⁹ In parallel to this, a separate prespecified analysis from an Ixekizumab trial assessed the association between Dermatology Life Quality Index improvements and levels of clinical response, and as expected, the quality of life improved as PASI index scores became higher. ¹⁰

Dr. Ortiz-Policarpio then proceeded to discuss how dermatologists and patients have different treatment goals. While dermatologists aim for improvement of symptoms alongside tolerability, and low risks of adverse effects as well as improved access to therapy, most patients only care about recovering quickly, this becomes the key to understanding patient compliance to treatment.

Efficiency of Ixekizumab

Ixekizumab’s mean time to achieve PASI 50 response ranged between 1.8 and 7.0 weeks, which is considered the most rapid response. The time to achieve clinically meaningful improvements, as defined by 25% of patients achieving PASI 75, ranged from 2.1-25.3 weeks. ¹¹ In a meta-analysis done on psoriasis randomized-controlled trials, it was concluded that PASI 100 rates were significantly higher with Risankizumab (RIS), Ixekizumab (IXE), Brodalumab (BRO) and Guselkumab (GUS) when compared to Etarnecept (ETN), Adalimumab (ADA), Ustekinumab (UST), Certolizumab pegol (CZP) and Tildrakizumab (TIL). IXE, RIS, BRO, and GUS had the highest PASI 100 rates at Weeks 10-16. ¹² Therefore, Ixekizumab undoubtedly allows patients to achieve a high PASI score in the shortest time possible.

The discussion then moved on to the safety of the drug. Adverse events were seen to be mostly mild to moderate injection-site reactions or hypersensitivity reactions. Rates of adverse events and discontinuation from treatment were consistently low through year 5. ¹³ 

Dr. Ortiz-Policarpio ended the lecture with a summary of what Ixekizumab can offer, further reiterating how this treatment is a promising solution to patients burdened by psoriasis.

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