What drugs target the T helper 1 (Th1) microenvironment?

From the Guidelines

Drugs that target the Th1 microenvironment include TNF-α inhibitors, JAK inhibitors, corticosteroids, and IL-12/23 inhibitors, which are commonly used to treat Th1-mediated autoimmune conditions. These medications work by interrupting the inflammatory cascade driven by Th1 cells, which otherwise leads to tissue damage and clinical symptoms in autoimmune disorders. Some of the specific drugs that target the Th1 microenvironment include:

• TNF-α inhibitors such as adalimumab (Humira, 40mg subcutaneously every 2 weeks), infliximab (Remicade, 3-5mg/kg IV at weeks 0,2, and 6, then every 8 weeks), and etanercept (Enbrel, 50mg subcutaneously weekly) 1
• JAK inhibitors like tofacitinib (Xeljanz, 5mg orally twice daily) and baricitinib (Olumiant, 2mg orally daily) which block the JAK-STAT pathway, disrupting Th1 cytokine signaling 1
• Corticosteroids such as prednisone (typically 5-60mg daily depending on condition severity) which broadly suppress Th1 responses
• IL-12/23 inhibitors like ustekinumab (Stelara, weight-based dosing) which target the Th1 pathway by blocking cytokines crucial for Th1 differentiation 1 The choice of medication depends on the specific condition, disease severity, patient comorbidities, and previous treatment responses. For example, in the treatment of psoriatic arthritis, the American College of Rheumatology and National Psoriasis Foundation recommend the use of TNF-α inhibitors, IL-12/23 inhibitors, and JAK inhibitors as first-line treatments 1. In addition, the British Association of Dermatologists guidelines for biologic interventions for psoriasis recommend the use of TNF-α inhibitors, IL-12/23 inhibitors, and other biologic agents for the treatment of moderate to severe psoriasis 1. Overall, the treatment of Th1-mediated autoimmune conditions requires a comprehensive approach that takes into account the specific condition, disease severity, and patient characteristics.

From the FDA Drug Label

The provided drug labels do not directly mention the Th1 microenvironment. The FDA drug label does not answer the question.

From the Research

Drugs Targeting the Th1 Microenvironment

• The Th1 microenvironment is associated with various autoimmune diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
• Several drugs have been developed to target the Th1 microenvironment, including:
  • TNF-α inhibitors, such as infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept 2
  • These drugs have been shown to be effective in treating autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, and chronic endogenous uveitis 2, 3
• Other therapeutic areas are under evaluation, including viral infections, such as COVID-19, and chronic neuropsychiatric disorders 2
• The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also ongoing 2

Mechanism of Action

• TNF-α inhibitors work by blocking the action of tumor necrosis factor-alpha (TNF-α), a key cytokine involved in the pathogenesis of immunoinflammatory diseases 2, 3
• The binding properties of adalimumab, infliximab, and etanercept to soluble and membrane TNF-α have been studied, with similar affinities and avidities observed 4
• Complement-dependent cytotoxicity (CDC) was induced in mTNF-transfected cells by adalimumab and infliximab, but not in activated normal human PBMC by any of the three agents 4

Efficacy and Safety

• Meta-analyses have compared the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis, with varying results 5
• Indirect comparisons of biological agents for the treatment of moderate-to-severe psoriasis have shown that ustekinumab, adalimumab, infliximab, and etanercept can be regarded as clinical equivalents, with choice depending on relative safety profiles, individual contra-indications, and cost effectiveness 6