Psoriasis Treatment: Ixekizumab

Psoriasis is a chronic autoimmune disease that affects about 2-4% of the world population, and those with psoriasis form patchy scales called plaques to form on the skin. Psoriasis is known to affect a patient’s quality of life, particularly those with moderate or severe psoriasis. This week, we summarize a recent study on SkinTherapyLetter reviewing Ixekizumab (Taltz™ in the US).

Psoriasis: Severity and Impact

Mild psoriasis is generally defined as covering less than 10% of the patient’s body, and thankfully, the majority of psoriasis patients fall into this category. Unfortunately about a third of patients fall into the moderate to severe involvement category. Although psoriasis is not a fatal disease, it has a serious impact on a patient’s quality of life, and is strongly correlated with depression and anxiety. Even mild cases of psoriasis can impact patients in very serious ways. Some of the ways in which psoriasis can negatively affect patients include:

  • Stigmatization and fear of contagion due to lack of public awareness and the visible nature of the symptoms
  • Direct symptoms including scaling of the skin (92%), itching (72%), redness (69%), fatigue (27%), swelling (23%), burning (20%), bleeding (20%)1
  • Psoriatic arthritis, which is painful and significantly reduces mobility, affects nearly a third of psoriasis patients
  • Links and comorbidities with other cardiovascular diseases
  • Effect on mental wellness, self-esteem, workplace and other social participation
  • Other impacts on daily living in a study includes clothing choice (54%), need for more frequent bathing (45%), more frequent washing of clothes (40%), sport activities (38%), sleep disorders (34%), inhibiting school or work activities (27%), sexual difficulties (27%), social relations (26%)2
  • Psoriasis on the arms, legs, and scalp are particularly concerning for patients as it is often uncovered making the symptoms more visible3

The Context Behind Biologics Treatment

Mild psoriasis is generally treated with topical medication and moisturizing. Phototherapy is also used when plaques cover a larger area of the body as topical treatment becomes less practical. For patients with moderate or severe psoriasis, and especially for those with psoriatic arthritis, systemic therapies are often used for treatment. These are administered orally or intravenously, and while they are powerful, generally, so are their side-effects. The general premise of systemic therapy is to suppress the immune system, which are thought to dysregulated in psoriasis patients, and the culprits behind the visible symptoms of psoriasis.

Ixekizumab is a member of the class of drugs called biologics, which are protein based drugs derived from living cells. The advantage of biologics compared to general immunosuppressants is that biologics have the ability to target very specific components of the immune system, rather than affect the entire immune system. In this case, Ixekizumab targets interleukin-17, which is thought to be a critical proinflammatory mediator for psoriasis. There are two other monoclonal antibodies that also target this pathway in the market, Brodalumab, and Secukinumab, adding weight to the evidence for this approach’s potential. Unlike topical medication which manages the visible symptom, these biologics have the ability to disrupt the process of psoriasis closer to the root of the problem, and are therefore effective against the arthritic component of psoriasis for patients with psoriatic arthritis as well. The main drawbacks with biologics is that they are extremely costly, and while targeted, it still does disrupt the immune response, and can cause increases in infections, and be contraindicated in some patients with active infections.

The Main Takeaways from the Study

The full study can be found here on SkinTherapyLetter.com, but there are some important findings that is sure to be exciting for those struggling with psoriasis or have friends and family that are struggling with psoriasis.

  • Given the success of drugs that target IL-17A, it’s becoming more evident that this cytokine plays an integral role in the pathogenesis of psoriasis.
  • The phase I-III trials unquestionably demonstrate promise of Ixekizumab in treating moderate to severe psoriasis.
  • Previous use of biologics has previously been shown to reduce efficacy of future biologics treatment. This has not been the case with Ixekizumab, which is significant for patients as psoriasis is a lifelong disease.
  • Long-term effects of inhibiting the IL-17A cytokine will require further research given its importance in immune function. There may also be concerns with depression that will require further research.

Background

  • Biologics target specific immunological pathways that create psoriasis.
  • Can treat moderate and severe psoriasis better than PUVA or topicals.
  • Interleukin 17 identified as a key pro-inflammatory mediator in psoriasis.
  • Ixekizumab an anti-IL-17 monoclonal antibody research in phase 1-3.
  • Can address underlying joint disease in psoriatic arthritis as well.
  • Plaques are caused by skin cells building up prematurely at the surface due to accelerated skin regeneration. “One of the cytokines produced by activated Th17 cells, IL-17A, is particularly central to the pathophysiology of psoriasis.”
  • Anti-psoriatic agents that target IL-17, a critical pathway, has become a research focus. There are currently 3 monoclonal antibodies targeting IL-17: Brodalumab, Secukinumab, and Ixekizumab.

Conclusions:

  • IL-17A is a critical cytokine in the pathogenesis of psoriasis. Data from late stage clinical trials from drugs that target this receptor (ixekizumab, brodalumab, secukinumab) and their effectiveness add further weight to the evidence.
  • Further studies will be needed to ascertain more precisely the role of IL-17 and Th17 cells to ensure safety and better understand risks of the class of IL17 inhibitors.
  • The clinical data suggest high levels of skin clearance for ixekizumab.
  • There is reason to be hopeful about research and development into this angle of treatment for psoriasis patients and dermatologists.

1WHO Report on Psoriasis: http://apps.who.int/iris/bitstream/10665/204417/1/9789241565189_eng.pdf
2Clearly, taken as a whole, psoriasis is life-altering for the majority of patients. http://apps.who.int/iris/bitstream/10665/204417/1/9789241565189_eng.pdf
3The sample is from members of psoriasis.org, which will likely skew towards people with more severe symptoms, but nonetheless important data. https://www.psoriasis.org/citizenpscientist/welcome
4http://www.skintherapyletter.com/2016/21.6/1.html