Table 1

Immunosuppressant versus immunomodulatory drugs and their actions. Immunomodulatory drugs are usually biological therapeutics with specific, extracellular effects on a particular pathway/cell type. Immunosuppressive drugs are small molecule therapeutics with selective effects on intracellular pathways. We have placed JAK inhibitors (and methotrexate) as immunomodulatory drugs because, to date, their risk:benefit profile aligns more precisely with this category

Immunosuppressant—broad effectsImmunomodulators—specific effects/anti-inflammatory
DrugEffectDrugEffect
AzathioprineMultiple—antiproliferativeTNF inhibitionSpecific cytokine blockade
MycophenolatePurine biosynthesis—antiproliferative, especially lymphocytesIL-6 receptor blockadeSpecific cytokine blockade
CyclophosphamideAlkylating agent—antiproliferativeRituximabB-cell depletion
CiclosporinCalcineurin inhibitor—inhibition of lymphocyte signallingAbataceptCostimulation blockade (T-cell modulator)
TacrolimusCalcineurin inhibitor—inhibition of lymphocyte signallingAnakinraSpecific cytokine blockade (IL-1)
GlucocorticoidsMultiple genomic effects on immune and inflammatory pathwaysIL-17 inhibitionSpecific cytokine blockade
SirolimusInhibits mTOR—inhibits lymphocyte signalling and activationMethotrexateFolic acid antagonist—precise mode of action in IMIDs uncertain
  JAK inhibitionSelective inhibition of lymphocyte signalling

  • IL, interleukin; mTOR, mammalian target of rapamycin.