Ankylosing spondylitis (AS) is a condition that leads to inflammation in the spine, hip bones, and other joints of the body, leading to pain and damage to the joints. There is no cure for the disease and inadequate understanding of its root cause. With ongoing research, scientists aim to uncover the underlying cause of the disease so that more effective drugs can be developed to slow, prevent or cure it.
Research into the causes of AS
Inflammation can be caused by the immune system reacting to a perceived threat. In conditions like AS, the immune system can mistakenly attack and damage healthy tissues. The reason why the immune system starts targeting the joints in AS is unknown.
Recent research has identified potential pathways and specific genes that play a role in the immune system and could be associated with AS. For example, particular forms of a gene called ERAP1 could be involved in AS, as it may affect the HLA-B27 gene, which is known to be associated with the condition. Another study identified that defects in a particular type of immune cell (called regulatory T-cells) could contribute to the development of the disease, and could be a therapeutic target.
As scientists uncover more genes that could be involved in AS, drugs that specifically target them can be designed. This could result in AS-specific therapies that are more effective at treating the condition.
Treatments in clinical trials
Currently, there are many new or repurposed drugs in clinical trials begin tested to determine if they are safe and have a clinical benefit in patients with AS. Many of these are new biologics, which block specific targets that are involved in the immune response. Examples of potential new treatments are described below.
Pfizer is testing its rheumatoid arthritis product, Xeljanz (tofacitinib citrate) as a potential AS treatment. Results of a randomized, double-blind, placebo-controlled Phase 2 clinical trial (NCT01786668), published in the scientific journal Annals of the Rheumatic Diseases, assessed Xeljanz in patients with AS. Findings suggested that the treatment was safe, and showed a clear reduction of symptoms in AS patients compared to a placebo.
Galapagos is developing filgotinib, a drug that inhibits the same target as Xeljanz. Filgotinib has shown positive results in patients with rheumatoid arthritis, and a Phase 2 clinical trial (NCT03117270) called TORTUGA is actively recruiting participants with AS to assess the safety and effectiveness of the drug.
AbbVie is planning a Phase 2b/3 trial (NCT03178487) called SELECT Axis 1 to test the safety and effectiveness of upadacitinib compared to a placebo in patients with AS.
Other examples include bimekizumab by UCB Biopharma being tested in Phase 2 clinical trial (NCT02963506), BCD-085 by Biocad (also in Phase 2 clinical trial) (NCT02763111) and Arcoxia (etoricoxib) by Merck Sharp & Dohme (NCT01327638).
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