PH9.1 | PH9.1 | Immunomodulators — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

Immunomodulators are divided into immunosuppressants and immunostimulants. Among immunosuppressants, calcineurin inhibitors (cyclosporine, tacrolimus) block the NFAT/IL-2 axis; antiproliferatives (azathioprine — IMPDH via 6-MP; mycophenolate — direct IMPDH inhibitor) block lymphocyte DNA synthesis; mTOR inhibitors (sirolimus, everolimus) block IL-2 downstream signalling; biologics (basiliximab, rituximab, infliximab, adalimumab) target specific surface molecules or cytokines; JAK inhibitors (tofacitinib, baricitinib) block cytokine signalling pathways. Standard transplant triple therapy = calcineurin inhibitor + antiproliferative + corticosteroid. Critical interactions: azathioprine + allopurinol → myelosuppression (reduce dose 75%); CYP3A4 inhibitors/inducers dramatically alter cyclosporine and tacrolimus levels. Anti-TNF biologics require pre-treatment TB and hepatitis B screening. Immunostimulants — interferons (antiviral, anti-tumour, MS), G-CSF (filgrastim — febrile neutropenia), IL-2 (aldesleukin — RCC, melanoma), BCG (intravesical bladder cancer) — augment immune responses. Common adverse effects: immunosuppressants → infections (PCP, CMV, TB reactivation, fungal); calcineurin inhibitors → nephrotoxicity; tacrolimus → NODAT; mTOR inhibitors → hyperlipidaemia, wound healing; interferons → flu-like syndrome, depression.

REFLECT

Consider a 50-year-old patient with long-standing RA who has been on methotrexate for 3 years with inadequate disease control. Her rheumatologist proposes adalimumab. As the prescribing physician, what is your checklist before writing the prescription? Which of the adverse effects discussed in this module concern you most for this patient? How would you counsel her about the risks and benefits? After reflecting on the immunomodulator pharmacology covered in this module, identify one clinical scenario from your recent ward rotations where an immunomodulator was used — can you now explain the mechanism and monitoring rationale?