In the run-up to his nationwide roadshow from October 6 to 8, 2020, Andreas Pinter, MD, University Hospital Frankfurt/Main, Germany, explained the importance of interleukin (IL)-23 inhibitors for modern psoriasis therapy and reported on his experience with this treatment option as well as on the wishes and expectations of his patients.
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
1. Since the discovery of IL-23 at the turn of the millennium, the role of this proinflammatory cytokine as a master regulator in the development of psoriasis has been identified [1, 2]. What does this finding mean for modern psoriasis therapy?
With the discovery of IL-23, a much more detailed insight into the pathophysiology of psoriasis has been gained. IL-23 is a very early proinflammatory cytokine. Its blockade makes it possible to intervene relatively early in the pathophysiology. The designation “master regulator” bears IL-23 quite rightly, because through its inhibition many other cytokines are subsequently suppressed, which in turn can have a very good and lasting effect in the fight against psoriasis.
2. How do the different IL-23 inhibitors risankizumab, guselkumab, and tildrakizumab differ in terms of their mechanisms of action?
Although the mode of action is the same for all three IL-23 inhibitors, there are nevertheless certain pharmacological and clinical differences. Thus, not every antibody has the same binding site on the cytokine, which is why IL-23 inhibition by different IL-23 inhibitors may vary. Although head-to-head data are not available, differences in effectiveness are seen. For example, the PASI 75, PASI 90, or PASI 100 response of tildrakizumab in phase III studies is somewhat less pronounced than that of risankizumab or of guselkumab [3-5]. There are also small differences in the half-life of the antibodies, which in turn is reflected in different injection intervals. Guselkumab has to be injected every eight weeks in the maintenance phase, tildrakizumab and risankizumab only every twelve weeks – this is a great advantage [3-5].
3. what is your practical experience in treating patients with moderate to severe plaque psoriasis with the selective IL-23 inhibitor risankizumab in terms of efficacy and tolerability [3]?
Risankizumab has now been on the market for just over a year. So far, even outside of clinical trials, I have been able to observe a very good, sometimes even excellent effect and all of my patients under Risankizumab have responded to the therapy. A large proportion of patients are even completely or almost completely free of appearances. So the effect is very convincing. In addition, no patient complains of relevant side effects, such as respiratory infections. Overall, I can observe a low rate of side effects, which was already present in clinical trials, in practice [3]. So in summary, my experience with Risankizumab has been very good – it’s very tolerable and very effective.
4. what do your patients expect from their psoriasis therapy nowadays and, based on the communication with your patients, how do you assess the therapy management in a treatment with risankizumab?
Of course, patients want an uncomplicated therapy that is effective and has few side effects. Risankizumab is one of the drugs that combine these properties. The three-month injection interval in maintenance therapy makes it very easy for patients, as they do not have to deal with the therapy at all in the meantime. In terms of effectiveness, as we see in both clinical trials and clinical practice, patients can also benefit greatly from the treatment. They can become appearance-free with risankizumab, which is what most patients expect from their therapy. And the side effect rate is also low, as already mentioned [3].
5. what makes the difference between a complete and an almost complete absence of appearance for the patient and what does this mean for the physician?
In any case, whether the skin has healed completely or only almost completely makes a difference [6]. Because if not all symptoms have disappeared, the patient does not have the certainty that his psoriasis is completely under control. Especially when there is a claim of complete freedom from appearance, residual skin symptoms are disturbing, even if they are only minor plaques. In addition, whether the plaques itch or burn and whether they are located in visible areas, such as the scalp or hands, play a role [7]. In this case, patients are even more uncomfortable if complete freedom from appearance is not achieved, and they may begin to cream or hide the affected areas again. And that is exactly what patients do not want, because they want a life without psoriasis [8]! Forgetting the disease is best accomplished with a complete Healing of the skin.
6. should the treatment of a patient with an absolute PASI > 3 who is satisfied with his current therapy be changed and how do you deal with such a patient?
Such a situation must be discussed individually with the patient. This is because how it is handled depends, among other things, on how severely the patient was affected when the pre-therapy was initiated. If someone was very severely affected, with a PASI 30 or above, and it was still reduced well, you don’t necessarily need to aim for a PASI < 3. Such special cases are certainly also well adjusted with a PASI < 5 or <8. In general, however, one should always check again whether the therapy goal could be achieved and how satisfied the patient is. If he is dissatisfied, for example, topical local therapies, such as creams or ointments, can be added to the treatment to achieve a PASI < 3. If such additional, rather conventional, therapies do not lead to the desired success, a short-term wait-and-see approach is certainly also a good option, as psoriasis also has a naturally fluctuating course. However, if psoriasis cannot be adequately controlled in the long term after a maximum of six months on a particular therapy, a switch to a drug with proven greater efficacy should be considered. However, one should not change the therapy too early, but give each drug at least three months to develop its effect. Because even though many drugs are now available, the treatment options are exhausted quite quickly. Overall, it would be desirable for the physician to seek discussion with the patient and, depending on the current therapy, to point out to him that more potent active substances may now be available. This could increase the motivation for a possible switch.
The continuation of the interview can be found here.
Literature
CH-SKZD-210046_08/2021
This article was written with the financial support of AbbVie AG, Cham.
