• Where are we with treatments for atopic dermatitis?

    AD is a disease that is fundamentally different from psoriasis, but also presents a high burden to patients, with severe interference in work capacity and ability to sleep. We are really just beginning to learn about AD, and there are currently no FDA-approved systemic drugs for the treatment of moderate to severe AD.

    One topical treatment for AD is crisaborole, a phosphodiesterase 4 inhibitor that is likely to hit US markets in 2016. PDE4 increases intracellular cyclic AMP, which can have an anti-inflammatory effect. Phase 2 data for an IL-31 monoclonal antibody, nemolizumab, were reported recently. IL-31 is discussed a lot in the genesis of itch, but it is not just itch: IL-31 is critical to barrier integrity and to the generation of anti-microbial peptides; it is a pro-inflammatory cytokine. In some patients, blocking IL-31 appears to improve itch rapidly but there are a few side effects such as edema that will need to be monitored.

  • How prevalent is depression in psoriasis and is it something that dermatologists should screen for routinely?

    Depression is very prevalent in psoriasis but the latest data suggest that there may be an association between skin clearance and improvements in depression, irrespective of the agent used to treat psoriasis. It is not entirely clear whether this is due to lessened systemic inflammation, cognitive function, or how patients feel about themselves. Nonetheless, depression is an important factor that should be screened, although this may be something that dermatologists are not comfortable doing. It is also important to emphasize that despite data suggesting psoriasis treatments can improve depressive symptoms, this does not necessarily translate into a reduction in suicides or suicidal ideation. Even the largest studies show that suicide remains rare yet unpredictable.

  • Tuberculosis appears to be less of an issue with IL-23 inhibitors. Will this be another convenience factor over other drugs?

    In addition to very impressive results in terms of skin clearance, the added convenience of IL-23 inhibitors is likely to set them apart from other treatments. Convenience is very important when considering treatments, and this will be especially relevant if a dermatologist is able to prescribe a biologic without the need for tuberculosis (TB) testing. The science also supports the concept that treatments targeting IL-23 can reduce side effects such as TB reactivation. Systemic cases of TB were a concern in the early days of anti-TNF therapy. However, by targeting cells and cytokines that are specifically relevant to psoriasis, such as IL–23-producing dendritic cells, there is the potential to remove some of the side effects seen with TNFα inhibition. It should be noted that IL-17 inhibition likely also presents a reduced risk of TB reactivation

  • What are the main challenges of palmoplantar disease?

    Pustular palmoplantar disease, with or without coexisting plaque-type psoriasis, presents a number of challenges, particularly in patients who have heavy coverage of palmoplantar pustulosis. It is important to understand the different types of palmoplantar disease: specifically, pure plaque psoriasis that occurs only on the hands and feet should be distinguished from psoriasis that occurs on the hands and feet as well as everywhere else. Many dermatologists may assume that if a drug were effective for plaques on the body then it would also be effective for plaques in the palmoplantar location. The patients who are most difficult to treat are those with plaques only on the hands and feet, as they are particularly resistant to treatment even with the most effective psoriasis drugs. That said, all the effective medications for psoriasis, old and new, conventional or biologic, may be effective for strictly palmoplantar disease.

    Palmoplantar psoriasis accounts for a great deal of absenteeism from work and reduced productivity, which is why additional patient-reported outcomes are important to consider when assessing outcomes. It can be particularly problematic to treat these patients in some countries, especially in the EU, as the patients do not have a PASI score of 10, meaning it can be difficult to get reimbursement.

  • Based on the currently available data, is it possible to say conclusively that anti-TNF treatment reduces major cardiovascular events?

    Although the latest observational data adds to a body of literature suggesting that aggressive treatment with biologics, such as TNFα inhibitors, may reduce future major adverse cardiovascular events (MACE), without randomized trials it is not possible to conclude too much. Much of the data come from commercial claims databases, which do not easily allow adjustment for potential confounding factors, such as BMI, family history or disease severity. Many people do not account for these caveats when interpreting the data and believe that as long as a patient is on an anti-TNF treatment they do not have to worry about MACE. This is the wrong message to convey—for example, a patient who is receiving a biologic therapy may have been seen more regularly and may have had their treatment managed by experts who are familiar with co-morbidities and ensure that the patient takes acetylsalicylic acid and statins, issues not reliably identifiable in claims databases. This alone could account for a major part of the observed protective effect.

    However, despite all the limitations, the body of observational data is quite compelling, and we repeatedly see reductions in MACE in the context of TNFα inhibitor treatment. Over the next 5 years, we will learn a lot more, as rigorous controlled studies investigating TNF inhibition as well as other mechanisms of action should clarify some of the prospective effects of biologics on inflammation.

  • Is inflammatory bowel disease a problem with IL-17 inhibitors?

    This is a controversial area: many people have differing opinions regarding the data. The absolute numbers of IBD cases reported in studies are very low and there is some debate over whether these truly represent an increase in risk. To interpret the data accurately, we need to take into account background rates of IBD, but research into this has been limited. In the future, it may be that we do not consider IBD a problem, but the current message should be to treat according to the label and exercise caution in patients with pre-existing IBD. Rationally, IL-17 inhibitors should not be first-line therapies in these patients.

  • Many people talk about immunogenicity with biosimilars; what happens in terms of switching?

    This is an important clinical question. Data suggest that immunogenicity is cross-reactive, which means that if you have secondary loss of a response due to anti-drug antibody production it is unlikely that it would be possible to change to a biosimilar and see a response. In other words, biosimilars will not allow a successful switch from the branded reference drug.

  • How do the improvements in work productivity seen with IL-17 inhibitors in psoriatic arthritis resonate in the clinic?

    Disability is one of the biggest issues in PsA, so if we can see patients functioning better that is a key benefit. However, one of the issues with IL-17 inhibitors is their likely position as second-line treatment, so what we really need to see are data for patients who have failed or had multiple exposures to TNFα inhibitors. Whether physicians use IL-17 inhibitors as a first- or second-line treatment will be very important, as second-line use in PsA is more complicated. In North America, we have not seen many of these studies, but in Europe this type of data is vital, particularly for payers.

  • For psoriatic arthritis, do the alternatives to anti-TNF treatment have the same level of effect?

    When a patient whose arthritis has been responding well to a TNFα inhibitor switches to a drug with a different mechanism of action, you often see a flare in disease. The current data do not provide the full clinical picture; however, alternatives to anti-TNF therapy, such as IL-17 inhibitors, do appear to work in PsA. Similarly, we can be optimistic about the efficacy of IL-23 inhibitors in treating PsA.