The Role of IL-17 in Papulopustular Rosacea and Future Directions

[Dan3dwards]

Rosacea is a chronic, progressive, inflammatory condition phenotypically subtyped into diagnostic features, major features, and minor/secondary features. There is currently no cure for rosacea, and it carries a significant negative psychosocial burden for afflicted patients. While there are a number of treatment modalities at the disposal of the clinician, clinical experience has suggested a need for updated treatments. The pathogenesis of rosacea is multifactorial; however, this paper will focus on the pivotal role of interleukin 17 (IL-17) in the development and progression of the disease. Furthermore, this paper will explore the mechanism of action of standard rosacea treatments and their effect on different stages of the IL-17 pathway. The standard treatments for rosacea are usually effective in controlling the symptoms of the disease in its mild-to-moderate form; however, their efficacy is diminished in the setting of severe and treatment-resistant rosacea. We hypothesize that IL-17 inhibitors, currently used successfully in psoriasis and psoriatic arthritis, could perhaps be used to treat severe and treatment-resistant papulopustular rosacea in the future; however, clinical trials and case reports will be needed to dictate expanded indications of IL-17 inhibitors. Furthermore, the high cost of IL-17 inhibitors presently prevents their use in disease states other than psoriasis or psoriatic arthritis

https://journals.sagepub.com/doi/abs/10.1177/1203475419867611?journalCode=cmsa

Here is a trial to cosentyx a psoriasis drug being used for rosacea. However there is no data on this as of yet.

https://clinicaltrials.gov/ct2/show/NCT03079531

I did however join a facebook group of users using cosentyx and ask if it has helped anybody with rosacea. Sadly the response wasn't that positive and a few users still had rosacea regardless of using cosentyx. This was of interest to me as I have both psoriasis and rosacea all over the centre of my face and it is difficult for me to know where the rosacea and psoriasis begin as the diseases appear to overlap according to my dermatologist.

[Dan3dwards]

I decided to go ahead and purchase the article mentioned above. Most of it covers similar aspects to a lot of papers on Rosacea. Although interestingly highlights that most current therapies like doxycycline or isotretinoin as well as topicals are all tackling the IL-17 pathway. Here is perhaps the most interesting aspect of the article below...

"Future Directions

Given the contribution of IL-17 to the development of PPR and the fact that current therapies already target the IL-17 pathway, perhaps IL-17 inhibitors can be used as a potential treatment for severe and treatment-resistant PPR. There is
currently 1 clinical trial in Phase 1b at Stanford University that is studying the use of secukinumab in moderate-tosevere PPR; however, preliminary results are not yet available from this study.43 IL-17 inhibitors have been used
successfully in psoriasis; however, their high cost represents a barrier to their use in other conditions.

There are 3 IL-17 inhibitors currently on the market—secukinumab (Cosentyx-Novartis), ixekizumab (Taltz-Lilly),and brodalumab (Siliq-Bausch Medical). Cosentyx has been on the market the longest, having been first approved by the Food and Drug Administration in January 2015. Taltz was approved next in March 2016, followed by Siliq in February 2017. Secukinumab is a recombinant human monoclonal IgG1/κ antibody that specifically binds to IL-17A.44 Ixekizumab has a similar mechanism of action but is a humanized IgG4 monoclonal antibody.45 Brodalumab, on the other hand, is a human monoclonal IgG2 antibody that bindsto IL-17RA, which is a protein expressed on the cell surface receptor utilized by multiple IL-17 cytokines.46 Brodalumab can thus block the action of IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25.46

All 3 agents have a similar side effect profile; however, brodalumab has a black box warning for suicidal ideation and behavior, including completed suicides.46 The best option for a patient has to be tailored to their individual
needs; however, brodalumab represents an attractive treatment option for severe rosacea as it blocks the action of a number of IL-17 cytokines. Secukinumab, on the other hand, has been studied for longer and may be the safest of the 3 to
administer if IL-17 inhibitors are used in the future to treat severe and treatment-resistant cases of PPR.

Conclusion
IL-17 plays a pivotal role in the development and progression of PPR, and current therapies already target different parts of the IL-17 pathway. Further studies and careful observation of patients with both psoriasis and rosacea on IL-17
inhibitors will dictate whether the indications for IL-17 inhibitors can be expanded to include treatment of severe and treatment-resistant PPR when traditional routes fail."