Better outcomes through innovative methods of therapy management

Personalized medicine is also becoming increasingly important in the field of inflammatory skin diseases. Currently, IL-17 and IL-23 inhibitors are most effective in moderate to severe psoriasis, but the response to therapy varies between individuals. Using molecular biological methods, a large number of characteristics can be correlated with the course of the disease and treatment, which is useful for individualized therapy management.

The question of how the treatment of immune-mediated diseases such as psoriasis can be further optimized is a research focus of Prof. Jo Lambert, MD, Department of Dermatology, University Hospital Ghent, Belgium. The expert reported on current projects dealing with the identification of treatment-relevant biomarkers and therapeutic drug monitoring [1]. The market launch of biologics has revolutionized the treatment options for psoriasis. The development of these modern antipsoriatic drugs is based on an increasing understanding of the pathophysiological processes. According to current research, psoriasis is an inflammatory autoimmune disease that is dominated by interleukin (IL)-17-producing T helper cells (Th17). In addition to TNF-α inhibitors and an IL-12/23 inhibitor, anti-IL-17 and anti-IL-23 antibodies in particular have raised the therapeutic goals to a new level in recent years, so that today PASI (Psoriasis Area and Severity Index)-90 or PASI-100 is often the declared goal [2]. Even though modern biologics are characterized by high response rates, particularly in clinical studies, inadequate treatment response in the sense of primary loss of efficacy (lack of clinical improvement or deterioration after initiation of treatment) or secondary loss of efficacy (lack of effect after initial clinical improvement) is repeatedly observed in everyday clinical practice and in case studies in some patients.

Identification of biomarkers for the prediction of therapy response

By definition, a biomarker is a measurable parameter that is correlated with the presence of a disease, a physiological change, a mental state or the response to treatment [3]. It is a truism that biomarkers are a key aspect in predicting treatment response. However, even though ^HLA-C*06:02 has been identified as the most important susceptibility allele in psoriasis and numerous other potential biomarkers are currently being researched, no biomarkers have yet been established for routine clinical use [4]. But there are numerous research projects dedicated to this topic. For example, as part of the BIOMAP (Biomarkers in Atopic Dermatitis and Psoriasis) project, large-scale analyses of clinical and molecular data were carried out to identify patient subgroups with different subtypes of the disease and different responses to therapy [4]. In a review article, Mortlock et al. The translational methods that can be used to determine treatment-relevant biomarkers in inflammatory skin diseases are summarized in Fig. 1 [5].

There are various methods to isolate biomarkers from the skin, including shave or punch biopsies or minimally invasive approaches such as tape stripping or superficial curettage. In addition, biomarkers can be determined in the blood serum. DNA/RNA analyses include techniques such as real-time (RT)-PCR, microarray, sequencing analyses or in situ analyses. Proteins can be analyzed by immunoassay, mass spectrometry-based methods, proximity extension assay or aptamer technology. The long-term goal is to use the RNA or protein levels of various immunological molecules or molecular correlates for a targeted selection of biologics therapy. This is still being tested experimentally.

Therapeutic drug monitoring: What is the optimal dosage?

“We need predictive biomarkers,” emphasized Prof. Lambert. However, there are cases in which the choice of medication is adequate and a lack of response is due to the dosage. “We use pharmacokinetics to control the dosage of biologics,” explained the speaker. Therapeutic drug monitoring can possibly contribute to a more targeted use of biologics, although the data on this in the indication area of psoriasis is still relatively limited. An international survey study showed that most dermatologists consider dose adjustments to be important and apply them in everyday clinical practice based on experience [6]. This is one of the key research areas of Prof. Lambert’s team (Overview 1) . “We have been working for several years to identify the therapeutic windows of opportunity for each biologic”. The aim is to determine the concentration of active ingredient required for an optimal therapy response.

Include patient-reported outcomes

The dysregulation of the immune system underlying psoriasis does not only affect the skin. Quite a few patients also develop joint involvement (psoriatic arthritis) [7]. In addition, comorbidities such as hypertension, dyslipidemia and diabetes occur more frequently in psoriasis patients [8,9]. This can have a significant impact on quality of life, with patients who show a good response to biologics generally also benefiting enormously in terms of quality of life – an important Patient-Reported Outcome (PRO). On the other hand, patient assessments can also be used to identify any need for change. It has been shown that the recording of PROs, in addition to classic clinical parameters such as severity and complication rates, contributes to an improvement in the quality of care as part of “value-based healthcare” [10,11]. Prof. Lambert reported that they use an encrypted web platform at their department, which patients can use to fill out questionnaires to evaluate the course of treatment and therapy results. This approach is being evaluated as part of the PsoPlus project, for example, in which psoriasis patients are cared for by multidisciplinary teams (“Integrated Practice Unit”). It has been shown that psoriasis patients with multiple conditions (e.g. psoriatic arthritis, obesity, chronic inflammatory bowel disease, smoking) in particular benefit greatly from this approach [12]. The T2T (Treat-to-target) project is also part of the “Value-based Healthcare” initiative, which aims to develop a target-oriented therapy strategy to facilitate joint decision-making between patients and medical professionals [13].

Congress: SGDV Annual Congress

Literature:

«Optimising treatment choices in psoriasis», Prof. Lambert, MD, SGDV Jahreskongress, Lausanne, 6.–8.9.2023.
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Corbett M, et al.: BIOMAP consortium. Biomarkers of systemic treatment response in people with psoriasis: a scoping review. Br J Dermatol 2022; 187(4): 494–506.
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