In a groundbreaking study presented at ACR Convergence 2022, the TMIC Li Node and pharmaceutical giant AbbVie have unveiled significant findings on the treatment of Ankylosing Spondylitis (AS), a chronic inflammatory disease. The collaboration centred on the drug Upadacitinib (UPA) and its effects on patients who have not responded adequately to nonsteroidal anti-inflammatory drugs (NSAIDs-IR).
What is Ankylosing Spondylitis (AS)?
Ankylosing Spondylitis is a form of arthritis that primarily affects the spine, although it can also impact other joints. It leads to inflammation of the vertebrae, causing pain and stiffness in the back and neck. Over time, this condition can lead to a fusion of the spine, significantly impacting a patient’s mobility and quality of life.
The Purpose of the Study
The primary focus of the study was to evaluate the efficacy of Upadacitinib, administered at a daily dose of 15 mg, in patients suffering from active Ankylosing Spondylitis. The research aimed to delve into how UPA influences the body’s global metabolome – the complete set of metabolites present in these patients.
Key Contributions by TMIC Li Node
The TMIC Li Node played a pivotal role in this research. Utilizing the CIL LC-MS metabolomics technique, the team meticulously analyzed serum samples collected at the baseline and two time points after the treatment. The process involved sophisticated labeling kits and the use of IsoMS Pro 1.2.15 software (NovaMT Inc.) for data analysis, ensuring precise identification of metabolites through the NovaMT Metabolite Database. This rigorous methodology led to the categorization of metabolites into three tiers based on their match to compounds in established libraries.
Results and Future Implications
The study’s findings are profound. A total of 8020 distinct metabolites were identified, shedding light on the biochemical pathways affected by UPA treatment. Notably, there was a significant impact on the histidine and tryptophan pathways. These changes correlated with improvements in clinical markers of AS, including CRP levels and the Ankylosing Spondylitis Disease Activity Score-CRP scores. Furthermore, histidine levels were linked to improvements in MRI spine indices, underscoring the potential of UPA in treating AS.
This comprehensive analysis is a first in the realm of metabolome studies in AS patients treated with UPA. It highlights the utility of advanced metabolomics in understanding how therapeutic agents work in this condition. The study particularly points to the tryptophan biochemical pathway, known to be involved in chronic pain and altered in AS patients, suggesting a novel mode of action for UPA in NSAID-IR AS patients.
The collaborative effort between TMIC Li Node and AbbVie represents a significant leap forward in understanding and treating Ankylosing Spondylitis. By unlocking the intricate biochemical pathways affected by UPA, this research not only paves the way for more targeted treatments but also exemplifies the power of advanced metabolomics in pharmaceutical research. The findings from this study open new doors for future research and offer hope for better management of this debilitating condition.
References:
Sornasse T, Li L, Zhao S, Wang X, Cai F, Bi Y, Song I, Wichuk S, Lambert R, Maksymowych W.Putative Role of the Histidine and Tryptophan Biochemical Pathways in the Mode of Action ofUpadacitinib in Patients with Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9).
