“No one needs to walk around with psoriasis these days”.

In the second part of his interview, Andreas Pinter, MD, University Hospital Frankfurt/Main, Germany, explains how IL-17 and IL-23 inhibitors differ in the treatment of psoriasis in terms of mechanism of action, clinical trial data, and applicability in practice, and how ambitious therapeutic goals can be better achieved in the future.

Dr. med Andreas Pinter Senior Physician Dermatology,

Head of Clinical Research and Head of Consultation for Chronic Inflammatory Dermatoses,

Clinic for Dermatology, Venerology and Allergology, University Hospital Frankfurt/Main

To the 1st part of the interview

1. IL-23 promotes the differentiation and maintenance of a pathogenic Th17 cell population and thus also supports the production of the proinflammatory IL-17, which is typical for psoriasis [1]. How do indirect inhibition of IL-17 by IL-23 inhibitors and direct IL-17 blockade by IL-17 inhibitors differ in terms of mechanism of action and effects on the immune response?

Here, pathophysiology plays a crucial role. Along with IL-23, IL-17 is one of the most important pathophysiological cytokines in psoriasis. If we block IL-17 directly by appropriate antibodies, for example secukinumab or ixekizumab, we achieve an anti-inflammatory effect very quickly [2]. By blocking IL-23, it is possible to reduce the number of IL-17-producing pathogenic Th17 cells or to induce them to undergo apoptosis. While this implies that it usually takes a little longer for IL-17 to be truly downregulated, and the time to response may be a few days longer than under IL-17 inhibitors [3-7]. However, it also means that IL-23 inhibitors have the more sustained effect [1], which is more significant than a rapid response in chronic disease.

2) How do you rate the recently published results of the head-to-head study IMMerge, which compared the efficacy and safety of risankizumab and the IL-17A inhibitor secukinumab in moderate to severe psoriasis [8]?

Of course, everyone is waiting for the results of such head-to-head studies between IL-23 and IL-17 inhibitors. The data from the IMMerge study are certainly among the most exciting study results that have been published recently in this regard. Because two very good and potent drugs are compared here. If you look at the data a little more closely, you can definitely see differences in response and dropout rates. Thus, more patients in the secukinumab arm dropped out of the study, perhaps because of side effects or waning efficacy, than in the risankizumab arm. Here, the rate of patients who completed the entire study period is significantly higher. In terms of effectiveness, exactly what would be expected from the mechanism of action can be observed. Initially, numerically, efficacy occurs slightly faster under secukinumab, but from week 20 onward, the response in terms of PASI 90 or 100 is significantly better under risankizumab. This gap splits significantly as we go along, so the data in week 52 is very meaningful. Here, one clearly sees a large difference of 30% in PASI 90 response between secukinumab and risankizumab. The data illustrate that early, rapid response with IL-17 inhibitors does not necessarily translate into a stable maintenance phase. Under IL-23 inhibitors, it may take a little longer to reach full efficacy, but this then remains stable over time. The side effect profiles of both drugs were comparable. I consider both secukinumab and risankizumab to be drugs with positive safety profiles and no new or serious side effects were observed [8].

3. how do the two therapy options differ in terms of their application and what does this mean for patients?

Both drugs are administered as a double injection, which is not a major problem for most patients. However, there is a big difference in the number and timing of injections. With secukinumab, the up-dosing phase is very intense during the first four weeks [6]. In contrast, with risankizumab, there is no intermediate injection during the first four weeks [3]. And also in the maintenance phase it makes a difference whether under secukinumab every four weeks or under risankizumab only once a quarter has to be injected [3, 6]. In total, patients receive 16 injections of secukinumab and five injections of risankizumab in one year [3, 6]. With longer intervals between injections, patients are much freer in how they manage their medication. And, of course, most patients like it uncomplicated [9]. For the physician, administration of risankizumab at the three-monthly checkup provides assurance that compliance is not a problem.

4. through what channels could patients be better informed about the options of available psoriasis therapies?

Independent reporting, independent media and independent sources of information are very important. There are several options here. For example, patient associations offer websites with good and independent information, where patients can also share their experiences with other sufferers. Certainly, the dermatologist should also be a good source of information, especially if he specializes in the therapy of psoriasis. In addition, print media that do good, independent reporting and provide information about novel treatment options or new scientific findings play an important role. Unfortunately, you can also find many sources with dubious information content on the net, which is not always obvious to the patient. That is why I advocate using official sources of information from the federal government or patient associations, for example at www.psori.ch.

5. what therapy goals would you like to see in psoriasis and how can HCPs, professional societies and pharmaceutical companies help to ensure that these goals are achieved in everyday practice?

In the short term, we have certainly fulfilled all wishes – for the first six to twelve months, most medications work very well. What we should focus on now is long-term therapy adherence. This means that we can get the patient on one drug and they are very well controlled under it for the next five to ten years with a low side effect rate. Here we still lack long-term data for some drugs – it would be immensely important to obtain them. It is also very important to me that we see patients early enough. There are many patients suffering from psoriasis who do not receive the appropriate therapies for years, if not decades. I would like to see better management of patient flow so that we can adjust patients to these therapies in a timely manner for better effect. Because the earlier we intervene therapeutically in the disease process, the better and the more long-lasting the effect. In addition, we should pay more attention to comorbidities in the future. Because if we initiate therapy early enough, we may be able to reduce certain comorbidities, for example psoriatic arthritis or a metabolic syndrome, which would be fantastic for the patients. To achieve these goals, efforts must come from all sides – from the medical profession, perhaps even from patients themselves, from patient organizations. A certain awareness has to be created: No one has to walk around with psoriasis these days, even though someone may have said so once. Although psoriasis still cannot be cured, it can be controlled very well. For further progress, we need good clinical trials, which can be initiated by pharmaceutical companies but also by independent professional societies.

6. what developments do you see in the future for psoriasis patients? Do you consider sustained complete freedom from symptoms to be a realistic goal in psoriasis therapy?

I believe that in the future we will be able to treat more and more patients in such a way that we achieve a lasting effect, perhaps even without sustained therapy. However, no data is currently available for this. Another important point is to perform good patient profiling, i.e. to predict the response to certain drugs based on certain markers and thus select the optimal treatment option. For this we also still need a lot of scientific data. Overall, I am very confident that the proportion of patients that we can control well and for a long time continues to increase.

Literature

This article was written with the financial support of AbbVie AG, Cham.