Stratified or personalised medicine in the treatment of psoriasis?

In the day to day management of patients with psoriasis, we try to find the optimal treatment for our particular patient, using a few general categories of disease severity and a therapeutic ladder with escalating therapeutic power: in mild psoriasis, topicals; in moderate psoriasis, phototherapy and subsequently classical systemics (fumarates, methotrexate, cyclosporin and retinoids); and in moderate and severe disease, biologics.

Evidence based guidelines have been developed to define the categories of disease severity; however, the definition of these categories of severity is extremely complex. Grosso modo, disease severity is assessed by objective severity criteria (PASI, BSA, PGA and others), subjective severity criteria (DLQI, EQ5D, etc), and assessment of historical severity (previous severe disease in the past and responsiveness to previous treatment) (1). The difficulty in disease assessment is that each of these three dimensions of severity assessment may be at variance with the others in the individual patient. For example, psoriasis involving one finger may be severe psoriasis in a violonist, while very extensive psoriasis responding well to a topical with remissions of many month resulting in a happy patient may be interpreted as mild psoriasis. A new aspect of our understanding is the appreciation of psoriasis as a multifaceted disease: highly variable responsiveness to treatments, comorbidities, large differences in the psychosocial context of the patient, and the differences in individual burden of the disease. As a doctor, I would say every patient has his her own disease, and I treat every patient with a personalised approach. It is an art to recognize the criticial individual elements and provide a tailored, optimal therapeutic solution addressing the patient’s needs and wishes.

As a chairman of a department of dermatology at a University hospital with a group of dermatologists and residents, I try to teach them the personalised approach. However, some degree of standardization of treatment selection is needed. It cannot be accepted that one doctor, stressing the presumed impact of psoriasis on quality of life in a patient with limited extend of psoriasis would prescribe an anti-IL17 treatment while another doctor would prescribe psychotherapy and a topical therapy to the same patient. We can appreciate the need for individualised care while recognizing the benefit of agreed upon guidelines of best practices.

As investigator and in my advisory role for positioning of new treatments, the question is what is the most appropriate window of severity in patients with psoriasis for a certain experimental treatment; in other words, what are the inclusion criteria with respect to severity for a new treatment? Should a drug be evaluated in severe disease or more moderate or mild disease? At present new treatments are appearing where most likely the appropriate indication is not severe psoriasis but more moderate disease. Fumarates do well as a first line systemic (2); experiences with apremilast suggest that this drug may perform better in patients who have not been exposed to systemics or biologics (3). The registration dossier of drugs should be compatible with the treatment guidelines.

It is the equilibrium between personalised and stratified care where we can individualise and standardize the treatment. A “contradictio in terminis” where we need creative doctors to find individual solutions and the context of standardization principles.