Choosing the right biologic in psoriasis

Biologic therapies for psoriasis are currently prescribed in a neither efficient nor cost-effective way. Disease endotypes, genotypes, cytokines, or patient baseline characteristics could allow for better guidance in treatment choice.

Therapeutic challenges in psoriasis management include disease clearance and maintaining remission effectively. New and developing insights into the aetiology of the condition, including the key genomic, immune, and environmental factors, have led to the development of precision therapies according to disease and drug endotype. Today, numerous biologics are approved with different targets. “However, it is critical to understand the real-world efficacy and safety profile of these agents,” said Prof. Nick Reynolds (Newcastle University, United Kingdom) [1]. In an analysis of the 3,523 biologically-naïve patients in the BADBIR registry, drug survival of ustekinumab was shown to be superior to etanercept, infliximab, and adalimumab –even after accounting for relevant covariates [2]. As Prof. Reynolds pointed out, studies like this will aid clinical decision-making when choosing biologic therapy for psoriasis patients.

Therapy according to disease endotype

Another way to choose the “right therapy” is to stratify response according to endotype analysis. An example of a successful therapy according to disease endotype is the inhibition of the interleukin(IL)-36 pathway for the treatment of generalised pustular psoriasis (GPP). Current genetic knowledge strongly links GPP to IL-36 signalling, and IL-36 is also highly expressed in GPP skin lesions [3]. In a first proof-of-concept study with 7 adults with moderate-to-severe GPP between 22 and 58 years of age, therapy with the monoclonal anti-IL-36 receptor antibody BI 655130 was remarkably successful. After a single dose of the antibody, all patients achieved a GPP Area and Severity Index Score of 0/1 (i.e. almost clear or clear skin) by week 4; 71% of patients already achieved this in week 1 or 2. Over 40% of patients were free of pustules within 2 days of treatment.

Another example of an endotype-driven selection of a biologic is the HLA-C*06:02 genotype, which is associated with a distinct psoriasis endotype. In an analysis of a psoriasis registry, with genome-wide genotype data of 1,326 patients, the HLA-C*06:02-negative patients were more likely to respond to adalimumab, whereas HLA-C*06:02-positive patients responded better to ustekinumab treatment [4].

Even certain cytokines can predict response to a biologic. In a trial published earlier this year, serum IL-19 levels at week 2 were predictive of outcome to ixekizumab at 16 weeks [5]. The lower the IL-19 levels were at 2 weeks, the better was the improvement in the Psoriasis Area and Severity Index (PASI) after 16 weeks.

Another analysis of the BADBIR registry showed that certain baseline characteristics are predictive of biologic treatment response [6]. The researchers investigated associations between 31 putative predictors and achievement of PASI 90 response at 6 months. In this analysis, white ethnicity was associated with a nearly 50% improved response, whereas obesity (>110 kg) and palmoplantar psoriasis were associated with significantly worse response. As Prof. Reynolds pointed out, the British Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium was founded to better understand determinants of response to biologic therapies and deliver, in close collaboration with commercial partners, a clinical test to predict response to biologic treatment in a cost-effective manner.

1. 
   
   1. Reynolds N. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
   2. Warren RB, et al. J Invest Dermatol 2015:135:2632-40.
   3. Bachelez H, et al. New Engl J Med 2019:380:981-3.
   4. Dand N, et al. J Allergy Clin Immunol 2019:143:2120-30.
   5. Konrad RJ, et al. Sci Rep 2019;9:5211.
   6. Warren RB, et al. Br J Dermatol 2019:180:1069-76.

 



Posted on 26 August 201918 March 2021