A review by Marije Koenders in Drug Design, Development and Therapy outlines some major features and characteristics of the new biological Secukinumab, which blocks the actions of interleukin 17A (IL-17), and explores its development, therapeutic potential and use in several rheumatic diseases.
IL-17 provides protection against extracellular bacterial and fungal infections. However, IL-17 and Th17 cells are perhaps the central drivers of inflammation in several chronic autoimmune and inflammatory diseases. The Th17–IL-17–IL-17R system has been implicated in psoriasis, psoriatic arthritis, rheumatoid arthritis, multiple sclerosis and Takayasu arteritis. This also includes autism, Guillain-Barré Syndrome and the meningeal remodeling and induction of tertiary lymphoid tissues (TLTs) formation during the early stages of EAE.
In the early 1990s, the remarkable therapeutic success of targeted inhibition of TNF-α in patients with rheumatoid arthritis have indicated that a selective targeting of cytokines may suppress inflammation and tissue destruction. Now, it appears that IL17 is a new therapeutic target in several common human maladies, and particularly rheumatic diseases.
Secukinumab (registered by Novartis with the brand name Cosentyx®) and ixekizumab are monoclonal antibodies (mAb) that inhibit interleukin-17A. These biologicals were recently approved for treatment of psoriasis, and secukinumab is also approved for treatment of two spondyloarthropathies, psoriatic arthritis and ankylosing spondylitis.
In the Drug Design, Development and Therapy review Marije Koenders summarizes some milestones in the development of secukinumab. As per this review Phase III trials proved the clinical efficacy of this anti-IL-17 antibody in psoriasis, followed by a rapid FDA approval of secukinumab for moderate-to-severe plaque psoriasis.
In rheumatoid arthritis, however, Phase II/III randomized controlled trials failed to demonstrate convincing data that secukinumab is effective in this condition. In contrast, Phase III trials appear to indicate that secukinumab is an efficacious treatment for psoriatic arthritis patients.
Moreover, it seems that secukinumab is also effective in ankylosing spondylitis – secukinumab is the first selective IL-17A inhibitor to meet primary endpoint in Phase III studies in active ankylosing spondylitis patients’. Most of the studies demonstrate a rapid and significant improvement of signs and symptoms, and importantly, a reduction of spinal inflammation as assessed by magnetic resonance imaging.
Thus, according to Marije Koenders the international treatment guidelines for various rheumatic diseases may need to be updated. Also secukinumab appears to be a novel class of drugs currently available for the treatment for several rheumatic diseases.
Source: Drug Des Devel Ther 2016; 10: 2069–2080
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