Rationale and Early Clinical Data on IL-17 Blockade in Psoriasis

Steven M Nwe; Amanda H Champlain; Kenneth B Gordon

Disclosures

Expert Rev Clin Immunol. 2013;9(7):677-682. 

In This Article

Expert Commentary & Five-year View

Clinical data on IL-17 blockade have definitely produced very encouraging results. If Phase II data is an indication, then IL-17 blockade not only has improved efficacy but also a much quicker response than its predecessors. Phase III data will attempt to look at long-term efficacy and safety in a much larger population, and, if positive, will be another good option for those suffering with moderate-to-severe plaque psoriasis. Data obtained will also reveal whether this target will be effective against psoriatic arthritis, of which there are currently very limited options.

The hope will be that targeting a cytokine further downstream on the Th17 pathway will provide a maximal benefit with a lower risk profile. Phase III trials for IL-17 blockade, influenced heavily by known risks of TNF blockade (infections, tuberculosis reactivation) and the possible increased MACE with IL-12/23 inhibition, have strict exclusion criteria that generate a participant pool that is generally healthier than the general psoriasis population.[63] While this ensures safety during clinical phases of drug development, it may underestimate the risks of using IL-17 blockade in psoriasis patients who have coronary artery disease risk factors once US FDA approved. This will also present a clinical challenge for clinicians who care for psoriasis patients (of whom many have concomitant coronary artery disease risk equivalents), who look to clinical trial data for risk/benefit assessments in these patient populations. Although this should not stop the further study of these agents, clinicians should consider the discrepancy between screened study subjects and the general psoriasis population prior to making informed decisions about patient treatment with IL-17 blockade, should these agents become commercially available.

In addition to assessments of long-term efficacies and risk profiles, further studies will help to better define IL-17's role in other inflammatory diseases. While the information presented thus far has shown impressive progress in psoriasis, early data of IL-17 blockade use in Crohn's disease and rheumatoid arthritis has not been as promising, revealing that there is still a lot to learn about the complex interactions of various immune cells and cytokines.[64]

As more information becomes available over the next few years, there will be important considerations on implementing trial data in real world settings. Should therapy prove effective and safe for psoriasis patients, successfully transitioning the medications to the clinic setting will require dermatologists to be more comfortable with prescribing biologic therapies as well as monitoring for systemic side effects. This somewhat reflects the dynamic evolution of dermatology in general, in which the understanding and treatment of skin disease will require a much deeper understanding of the systemic interactions that cause the skin manifestations themselves. In addition to gaining comfort in treating psoriasis with increasingly novel and systemic treatments, dermatologists will also need to address access-to-care issues that often limit the sickest psoriasis patients from being able to benefit from the most effective therapies. All this being said, data from IL-17 blockade for use in moderate-to-severe plaque psoriasis and psoriatic arthritis appears positive and if it continues on this trajectory, it will become a very meaningful therapy option for those treating and living with these diseases.

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