How to personalize the treatment of psoriasis with biologics?

A repertoir of biologics is available for the treatment of psoriasis and new biologics are in different phases of development. The question arises do we need all these? In other words: can we simplify the selection of treatments by reducing the number of available treatments by reconciling efficacy/safety ratio and costs?

Evidence-based medicine

In times of evidence-based medicine treatment selection is guided by best available evidence. In psoriasis, the number of controled comparative studies is limited. In the field of current biologics, head-to-head comparative studies are exemplary: etanercept against ustekinumab (1,2). Although the evidence is not available to justify the treatment selection based on comparative studies, we know from the randomized controled studies that efficacy is lowest with etanercept and is higher for the TNF antibodies and ustekinumab.

The other side of the coin is safety? Adverse effects of the various biologics have been studied in randomized controled clinical trials and in patient registries. Again no signal is available that one of the available biologics has an advantageous safety profile (2,3).

Based on safety and efficacy, a preference for one biologic in the treatment of psoriasis is not apparent.

There has not been shown a statistically significant difference with respect to safety or efficacy between the biologics in the treatment of psoriasis.

Cost effectiveness

The question arises whether treatment selection can be restricted to a limited number of biologics based on costs?

The value of a biologic can be estimated based on improvement of health-related quality-of-life measures over time. This value has to be balanced against costs. Healthcare authorities have calculated the incremental cost effectiveness ratio (ICER) for the different biologics. Willingness to pay had been given based on the ratio health gain/costs. ICERs for different biologics used in the treatment of psoriasis range from Pounds 30 111 and Pounds 40 250 (4). It can be seen that there is no preference for one single biologic, based on healthgain/costs.

Personalized biologics

In real clinical practise, the personalization of treatments has always been the medical art. To find out the most optimal treatment for an individual treatment is the ultimate significance of medical intervention.

Responsiveness to a treatment may differ from patient to patient and even within the same patient during life. Such cannot be predicted so far, although the historical responsivess to the various treatments, so far, may be our best guide.

In addition, the matching of co-morbidities of the patiënt with the potential side effects of the drugs is the other principle in discovering the right treatment in the individual patient (5). Recently, the value of ustekinumab in psoriatic arthritis was shown (6). Comparing these data with other studies on anti-TNF treatments, one may conclude that anti-TNF is prefered above ustekinumab in patient with active psoriatic arthritis, except in the situation of severe dactylitis and tendinitis, where ustekinumab has been shown to reach a similar efficacy. Comparative studies are lacking so far. In patients with increased risk for demyelinating disease, for example, a positive family history, ustekinumab is prefered above anti-TNF (5). In patient with metabolic syndrome and cardiovascular risk factors, no solid evidence exist that a biologic should be preferred above other treatments. However, in a patient with congestive hartfailure (NYHA grade III or IV) TNF-blockers are contra-indicated and ustekinumab is permitted (5). In patients with malignancies and infections, biologics should be avoided as much as possible. At present, there is circumstantial evidence that anti-TNF antibodies have a more robuste immunosuppressive effect as not only soluble but also membranebound TNF is inhibited. Furthermore, complement-dependent cytotoxicity and antibody-dependent cytotoxicity and reversed signalling are associated with the TNF antibodies and not with the etanercept.

Intermittent treatment with biologics may be anticipated. In particular, in women with pregnancy wish, in patients who will need in future surgery or life vaccin, or in patients who may suffer from intercurrent infections, etanercept will be prefered as the biologic with the shortest elimination half-life and the biologic with a very low degree of immunogenicity.

Future perspectives

The horizon of treatments in psoriasis is broadening. New small molecules with new modes of actions such as Janus kinase inhibitors and phosphodiesterase inhibitors are in clinical trial. Anti-IL17 treatments are in various phases of the development. The repertoir of treatments in psoriasis will broaden.

It will be the challenge and the opportunity to match the best treatment for the individual patient and not to select one treatment for the average patient as the average patient does not exist.

Declaration of interest

Prof. Dr. P.C.M. van de Kerkhof has consultancy services for: Celgene, Centocor, Allmirall, Amgen, Pfizer, Philips, Abbvie, Ely Lily, Galderma, Novartis, Jansen Cilag, Leo Pharma, Sandoz, Mitsibishu, Sandoz. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.