Complete skin clearance and beyond.

Before the introduction of biologics, the treatment of moderate to severe psoriasis was Sisyphean. Today, interleukin (IL) inhibitors have made it possible in many cases to achieve complete skin clearance/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100). To investigate which IL inhibitors are most potent at the group level is essential. Randomized controlled trials show their particular strength in the head‐to‐head setting – the collection of real‐world evidence in this domain is not trivial. However, head‐to‐head trials are unfortunately rare, giving the article by Richard Warren et al. from Manchester in this issue of the BJD particular importance.

The AbbVie‐funded, multicentre, phase III, randomized open‐label, efficacy‐assessor‐blinded trial (IMMerge) compared both efficacy and safety between the IL‐23 inhibitor risankizumab (Skyrizi®, AbbVie) and the IL‐17 inhibitor secukinumab (Cosentyx®, Novartis) under 1 year (52 weeks) of treatment in a total of 327 included patients. Risankizumab met both primary endpoints – it was, in the proportion of patients achieving PASI 90, both noninferior at week 16 and superior at week 52. Even the secondary endpoints were met by risankizumab, including PASI 100 at week 52. That risankizumab only needs to be administered after initiation every 12 weeks (secukinumab every 4 weeks) is an additional advantage.

With several new molecules in each class of biologics it is not feasible to have evidence from comparative studies for all molecules. However, it is hazardous to regard one molecule as representative for a class. Correctly, the authors did not speculate on class effects but clearly restricted their conclusions to risankizumab vs. secukinumab. We know from everyday practice that patients may have a very different response to molecules within one class. To build evidence for personalized medicine, patient registers are of utmost importance to understand the therapeutic effectiveness of the various molecules in real life.

Two patients treated with risankizumab experienced nonfatal myocardial infarctions confirmed as major adverse cardiovascular events (MACEs) (no MACE occurred in patients treated with secukinumab). Both patients had a smoking history extending decades. Neither event was considered to have a causal relationship with risankizumab treatment, and both patients remained in the study without treatment interruption. The authors conclude that no new safety signals were detected during this trial, which is correct, as MACE signals for risankizumab were described in independent trials before. , At this stage, it is of course difficult to exclude a causal relationship between risankizumab and MACEs in particular risk groups – careful follow‐up in phase IV studies have to address this question. Patient registries are important here, too, to capture these rare adverse events and to retrieve the information for all molecules within each class of biologics.

But, in a larger sense, this study confronts us with the paradox of the interleukin era – that a patient with psoriasis who has achieved complete skin clearance is not necessarily healthy. This is particularly important now as the Coronavirus disease 2019 (COVID‐19) pandemic clarifies the vital importance of general health and fitness. In the delicate interplay between psoriasis of the skin, and somatic and psychiatric comorbidity, we cannot take comfort in the belief that pharmaceutical psoriasis treatment will also take care of comorbidities. In particular, as this study insinuates, pharmaceutical psoriasis treatment will not be able to compensate for poor lifestyle choices such as smoking.

Are we not obligated to explain to a patient with, for example, a MACE risk that we can treat the skin successfully with IL‐inhibitors, but that her overall health needs to be improved by optimizing lifestyle factors too?

We dermatologists are often the central caregiver for patients with psoriasis, and we interact directly with our patients. In this encounter, an excellent opportunity arises to raise and discuss health challenges beyond the skin. Let us be ambitious in the management of psoriasis, aiming for clear skin, optimal quality of life and last, but not least, optimal health in its broadest sense.

Author Contribution

Marcus Schmitt‐Egenolf: Conceptualization (equal); Writing‐original draft (equal); Writing‐review & editing (equal).