Intermediate monocytes are possible predictors of response to secukinumab

Research on various types of cells from the myeloid lineage found that the frequency of intermediate monocytes at baseline differs significantly between responders and non-responders to psoriasis therapy with secukinumab. This could lead to the use of intermediate monocytes as a biomarker for treatment success.

Dr Jonathan Hardman-Smart (King’s College London, UK) highlighted the clear need for stratification in psoriasis treatment [1]. Although the biologic armamentarium offers a wide range of drugs that have proven substantial efficacy, a lack of biomarkers exists for the prediction of treatment success. The objective of the Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium is to identify predictors of response, which may include clinical, pharmacological, and genetic markers, as well as blood immune monitoring. For example, previous PSORT research identified an association between baseline NF-κβ signalling in type-2 dendritic cells and an absence of clinical treatment response to adalimumab [2].

Dr Hardman-Smart presented new research that enrolled 17 patients from the SIGNATURE (NCT01961609) study and evaluated immunophenotyping of psoriasis patients receiving therapy with secukinumab [1]. SIGNATURE participants had been non-responders to TNF-blockers for psoriasis. “Real-world data has shown that about 57% of patients will achieve a 90% reduction in their Psoriasis Area and Severity Index (PASI) or achieve PASI 90 by 12 months of treatment. However, this means up to 40% of patients may not respond adequately to treatment,” Dr Hardman-Smart indicated.

From baseline blood samples and blood drawn after 12 weeks of secukinumab treatment, peripheral blood mononuclear cells, including myeloid cells, were isolated for further investigation. These comprised markers for plasmacytoid dendritic cells, myeloid dendritic cells, and also monocytes and subsets. Different types of monocytes express different levels of CD14 and CD16: classical monocytes are highly positive for CD14 but negative for CD16, non-classical in contrast show high levels of CD16 and low levels of CD14, while intermediate monocytes express little CD16 and much CD14. “We included these in our panel because it has recently been shown that monocytes express IL-17 receptor. Moreover, IL-17 promotes an inflammatory phenotype in monocytes and causes them to home to skin or tissue specifically,” Dr Hardman-Smart stated.

Monocyte subsets: the key to secukinumab response

Overall, the rates of plasmacytoid dendritic cells, myeloid dendritic cells, and monocytes did not change in the wake of secukinumab therapy. “However, when we broke this down and looked into the monocytes subsets, we found some interesting trends in the classic monocyte population and intermediate monocyte population but not in the non-classical monocytes,” Dr Hardman-Smart uncovered. Differentiating further between responders with PASI 75 and non-responders at week 12, a significant decrease was found in classical monocytes in responders together with an increase in intermediate monocytes (P<0.01 for both changes). This phenomenon was not seen in non-responders. Of note, responders already had a significantly higher percentage of classical and a lower rate of intermediate monocytes at baseline compared with non-responders (P<0.01).

But what about prediction of treatment response? “We first used a percentage relative PASI. This is a measure of an individual’s residual psoriasis based on week 12, and what we found was a significant correlation with the baseline frequency of intermediate monocytes and clinical response,” Dr Hardman-Smart explained. Testing the predictive validity of the baseline frequency of intermediate monocytes at a certain cut-off, the receiver operator analysis led to a sensitivity of 100%, a specificity of 83.3% and an area under the curve of 92.4% with a P-value of 0.0056. According to Dr Hardman-Smart, these are promising results.

The researchers concluded that these results suggest that the frequency of monocytes subsets before therapy may be an immune determinant of clinical response to secukinumab, which could be exploited as a predictive biomarker.

 

1. 
   
   1. Hardman-Smart JA, et al. Relative frequency of monocyte subsets at baseline in psoriasis is associated with clinical outcome to secukinumab therapy. FC26, Psoriasis Gene to Clinic Congress 2021, 9-11. December.
   
   
   2. Andres-Ejarque R, et al. Nat Commun. 2021;12(1):4741.

 

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Posted on 2 February, 2022