Will JAK inhibitors for inflammation expand mkt presence?

Heads Up and Level Up sub-analysis studies confirm Rinvoq's advantage

Evidence for treatment selection is used after the approval of switching between drugs as of March

It has been confirmed that Janus kinase (JAK) inhibitors are more effective at rapidly and powerfully controlling inflammatory responses in atopic dermatitis compared to biologics.

 

Now that switching therapies between different drug classes is allowed, this finding is expected to serve as a key basis for drug selection in clinical practice.

 

According to the pharmaceutical industry, on May 26, the Ministry of Health and Welfare (MOHW) revised reimbursement criteria as of March, allowing for the switching of therapies between JAK inhibitors and biologics for the treatment of atopic dermatitis.

 

Subsequently, clinical settings will have to consider treatment strategies following reimbursement approval for switching between drug classes.

 

Recently, the results of sub-analysis studies, Heads Up and Level Up clinical trials, were reported.

 

The study involved a comparison between the JAK inhibitor Rinvoq (upadacitinib, AbbVie) and the biologic dupilumab.

 

This research not only showed that Rinvoq rapidly and strongly suppresses Type 2 inflammatory responses, a core pathogenesis of atopic dermatitis, but also effectively controls other significant inflammatory responses related to atopic dermatitis, such as Type 1 and Type 17/22 responses.

 

Specifically, in the sub-analysis of the Heads Up study, at week 2 of treatment, the gene expression patterns (transcriptomes) in the skin of the Rinvoq group were approximately 66.5% similar to those of normal skin.

 

In contrast, dupilumab's transcriptome normalization was only 2.0% (P < 0.001).

 

At week 16 of treatment, the level of transcriptome normalization was 104.4% for the Rinvoq group and 62.9% for the dupilumab group, with the Rinvoq group showing significantly higher efficacy (P<0.0001).

 

Furthermore, Rinvoq demonstrated superior efficacy to dupilumab in inhibiting IL-13 (like IL-4 involved in Type 2 inflammation that causes skin barrier destruction, inflammation, and itching) and CCL17 (TARC), a cytokine involved in Type 2 inflammatory responses that amplifies these reactions.

 

Similar results were observed in the sub-analysis of the Level Up study, presented at the AAD (American Academy of Dermatology Annual) meeting held in March this year.

 

In this study, both the Rinvoq and dupilumab groups showed a reduction in cytokines related to Type 2 inflammatory responses (CCL17/26, eosinophil count).

 

However, the reduction in cytokines related to Type 1 inflammatory responses (CXCL10) and Type 17/22 inflammatory responses (IL-22, BD2) was greater in the Rinvoq group than in the dupilumab group.

 

Notably, patients in the Rinvoq group who achieved nearly clear skin (EASI 90) showed significantly greater reductions in cytokines such as IL-22, BD2, and CXCL10 compared to those who did not.

 

They also had lower levels of Type 2 inflammatory response-related cytokines like CCL17 and CCL26.

 

Dr.

 

Min Kyung Shin (Dermatology) at Kyung Hee University Hospital said, "Atopic dermatitis is a disease involving complex immune responses.

 

Rinvoq has demonstrated in clinical studies that it can rapidly and powerfully control not only Type 2 but also various other inflammatory responses, making it an optimal drug for managing atopic dermatitis patients to recover their daily lives quickly." Dr.

 

Shin further projected, "Rinvoq, which can control a broader range of inflammatory responses, may be more effective even in patients who do not respond to biologics.

 

Given that reimbursement for switching between atopic dermatitis treatments has recently been approved, drug prescriptions can now be made according to the patient's condition."