Tetra Therapeutics, a clinical-stage biopharmaceutical company developing novel treatments for patients with cognitive impairment and memory loss, today announced a poster presentation at the 12th Clinical Trials on Alzheimers Disease Meeting (CTAD) being held in San Diego, from December 4 “ 7.
The poster, titled Tumor Necrosis Factor (TNF) Blocking Agents Reduce Risk for Alzheimers Disease in Patients with Rheumatoid Arthritis and Psoriasis, highlights data from a retrospective population-based study of 56 million patients in which inflammatory disease in the body is shown to increase risk for Alzheimers disease and that risk can be reduced in these patients by treatment with a TNF blocking drug. The study was conducted in conjunction with Case Western Reserve University.
Our analysis demonstrates the value of a large, population-based database covering 20% of the entire US population. We find that inflammation in the body increases risk for Alzheimers disease across multiple diseases involving the joints, the gut and the skin, said Mark E. Gurney, Ph.D., Chairman and Chief Executive Officer of Tetra Therapeutics and co-author of the study. The study further indicates that the risk for Alzheimers disease can be reduced in patients with rheumatoid arthritis and psoriasis by treatment with TNF blocking agents such as etanercept, adalimumab, and infliximab. The results of our retrospective study need to be validated by well-controlled, prospective studies, but offer the hope that Alzheimers disease can be prevented in some patients in whom an inflammatory disease is a risk factor for developing Alzheimers disease.
The study used the de-identified population-level, electronic health records of 56 million unique patients collected by the IBM Watson Health Explorys Cohort Discovery platform from 360 hospitals and 317,000 providers. The study evaluated patients with inflammatory diseases (including rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ulcerative colitis, and Crohn’s disease). The study examined whether these systemic inflammatory diseases – which in part are mediated by tumor necrosis factor (TNF) – increased the risk for Alzheimers disease and whether or not risk could be mitigated by an FDA-approved, TNF blocking biologic drug.
The study findings are exciting in that we clearly see that TNF blocking agents reduce the risk for co-morbid Alzheimers disease in real-world patients diagnosed with rheumatoid arthritis or psoriasis, said Rong Xu, Ph.D., Associate Professor, Department of Population and Quantitative Health Sciences, School of Medicine at Case Western Reserve University and co-author of the study. Given that anti-TNF biologics are powerful drugs, we believe further prospective studies are necessary to understand their potential in treating or preventing Alzheimer’s disease.
The analysis compared a diagnosis of Alzheimer’s disease as an outcome measure in patients who received at least one prescription for a TNF blocking agent (etanercept, adalimumab, and infliximab) or for methotrexate.
Alzheimer’s risk was increased in adults with the following diagnoses (all P<0.0001):
- Rheumatoid arthritis: adjusted OR 2.06 [95% CI 2.02-2.10]
- Psoriasis: adjusted OR 1.37 [95% CI 1.31-1.42]
- Ankylosing spondylitis: adjusted OR 1.57 [95% CI 1.39-1.77]
- Inflammatory bowel disease: adjusted OR 2.46 [95% CI 2.33-2.59]
- Ulcerative colitis: adjusted OR 1.82 [95% CI 1.74-1.91]
- Crohn’s disease: adjusted OR 2.33 [95% CI 2.22-2.43]
- Rheumatoid arthritis patients treated with etanercept (adjusted OR 0.34 [95% CI 0.25-0.47]), adalimumab (adjusted OR 0.28 [95% CI 0.19-0.39]), or infliximab (adjusted OR 0.52 [95% CI 0.39-0.69]) had a reduced risk of Alzheimer’s. Methotrexate also reduced Alzheimer’s disease risk, especially for patients who had a prescription history for both a TNF blocker and methotrexate.
- Psoriasis patients treated with etanercept (adjusted OR 0.47 [95% CI 0.30-0.73]) or adalimumab (adjusted OR 0.41 [95% CI 0.20-0.76]) also had a reduced risk for Alzheimer’s disease.
- Sex or race did not affect the results, but younger patients showed greater benefit from a TNF blocker than older patients
About Alzheimers Disease and Tumor Necrosis Factor (TNF)
Alzheimers disease (AD) is the most common cause of dementia. Multiple lines of evidence indicate that TNF may trigger or amplify aberrant microglia signaling in the brain and thereby contribute to AD pathogenesis. Systemic inflammatory diseases affecting the joints, skin and gut are caused in part by the production of TNF by activated macrophages and these diseases can be treated effectively with a TNF blocking agent. Furthermore, systemic TNF can access the brain through receptor-mediated transcytosis. In the brain, elevation of tumor necrosis factor (TNF) in cerebrospinal fluid collected from subjects with mild cognitive impairment is associated with progression to AD at 6 months follow up.
About Tetra Therapeutics
Tetra Therapeutics is a clinical stage biotechnology company developing a portfolio of therapeutic products that will bring clarity of thought to people suffering from Alzheimers disease, Fragile X Syndrome, traumatic brain injury, and other brain disorders. Tetra uses structure-guided drug design to discover mechanistically novel, allosteric inhibitors of phosphodiesterase 4 (PDE4), an enzyme family that plays key roles in memory formation, learning, neuroinflammation, and traumatic brain injury. Tetra Therapeutics is headquartered in Grand Rapids, Michigan. For more information, please visit tetratherapeutics.com.