IL-17 Antibody Dosing Regimens for GPP Treatment
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Solution Overview
Problem
Current treatments for Generalized Pustular Psoriasis (GPP) have limited options and significant side effects, with existing therapies like corticosteroids, ciclosporin, etretinate, and infliximab facing issues such as long-term toxicity, teratogenicity, and loss of response due to neutralizing antibodies.
Innovation Solution
Administering an IL-17 antibody or antigen binding fragment, such as secukinumab, which binds to an IL-17 homodimer epitope and has a dissociation constant of about 100-200 pM, given subcutaneously in specific dosing regimens to manage GPP, including initial doses at weeks 0, 1, 2, and 3, followed by monthly dosing, with potential up-titration based on clinical assessments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional treatments like corticosteroids, ciclosporin, etretinate, and infliximab are used for GPP, then treatment efficacy is achieved, but significant side effects and long-term toxicity occur
Solution Approach 1:
The patent extracts and targets the specific pathological mechanism of GPP by blocking IL-17 signaling pathway. Instead of using broad-spectrum immunosuppressants that affect multiple systems, the invention specifically extracts and inhibits the IL-17 cytokine pathway that is directly involved in pustular psoriasis pathogenesis, thereby achieving treatment efficacy while minimizing off-target side effects
Solution Approach 2:
The patent changes the therapeutic parameter from non-specific immunosuppression to specific cytokine pathway blockade. By targeting IL-17 with monoclonal antibodies or small molecule inhibitors, the treatment parameter shifts from affecting multiple immune pathways to specifically modulating the IL-17 signaling pathway, reducing harmful effects while maintaining efficacy
2Reliability
If infliximab and other TNF-α antagonists are used for GPP, then treatment success is achieved, but loss of response occurs due to development of neutralizing antibodies
Solution Approach 1:
Instead of continuing to use TNF-α antagonists that induce neutralizing antibodies leading to loss of response, the patent inverts the approach by targeting a different cytokine pathway (IL-17) that is also involved in GPP pathogenesis. This alternative pathway targeting avoids the antibody-mediated resistance problem while maintaining treatment efficacy
Solution Approach 2:
The patent changes the therapeutic target parameter from TNF-α to IL-17, shifting the mechanism of action to a different cytokine pathway. This parameter change avoids the development of neutralizing antibodies against TNF-α antagonists and provides sustained long-term response duration
3Reliability
If etretinate is used for GPP treatment, then therapeutic effect is achieved, but teratogenicity and long half-life cause treatment discontinuation
Solution Approach 1:
The patent extracts and targets the specific inflammatory pathway (IL-17) responsible for GPP pathology, replacing systemic retinoid therapy with pathway-specific blockade. This extraction of the specific pathogenic mechanism allows for targeted intervention without the broad toxic effects of etretinate, including teratogenicity and accumulation in body tissues
Solution Approach 2:
The patent employs biologics and small molecule inhibitors with appropriate pharmacokinetic profiles that do not accumulate in the body like etretinate. These agents have shorter half-lives and are cleared from the system without long-term accumulation, eliminating the need for prolonged discontinuation periods before conception while maintaining therapeutic efficacy
Data Source
AI summary
The disclosure is directed to methods, treatment regimens, uses, kits and therapies for treating Generalized Pustular Psoriasis (GPP). These methods, treatment regimens, uses, kits and therapies utilize, inter alia, administration of an IL-17 antagonist, e.g., an IL-17 antibody, such as secukinumab. Additionally disclosed are improved methods for treating plaque-type psoriasis that utilize up-titration and down-titration of the IL-17 antagonist, e.g., an IL-17 antibody, such as secukinumab, as well as modification of dose frequency. Further disclosed are methods of treating palmoplantar pustular psoriasis using the disclosed IL-17 antagonists, e.g., IL-17 antibodies, such as secukinumab.