Principle actions of common immunosuppressive agents

Overview

Immunosuppressive/disease-modifying drugs used in rheumatology act at distinct points of the immune response - broadly grouped into conventional synthetic DMARDs, biologics (targeting specific cytokines/cells), and targeted synthetic DMARDs (small-molecule inhibitors) - drug choice follows from which pathway predominates in the specific disease
Forms the core pharmacological toolkit across essentially all inflammatory rheumatic disease management, with an expanding range of targeted options developed over the past two decades

Class	Example	Mechanism
Conventional synthetic DMARD	Methotrexate	Antifolate/anti-proliferative and anti-inflammatory effects on immune cells
Conventional synthetic DMARD	Hydroxychloroquine	Interferes with antigen presentation/TLR signalling
TNF inhibitor	Adalimumab, etanercept	Blocks TNF-alpha
IL-6 receptor inhibitor	Tocilizumab	Blocks IL-6 signalling
B cell depletion	Rituximab	Anti-CD20, depletes B cells
T cell co-stimulation blockade	Abatacept	Blocks the CD28-CD80/86 co-stimulatory signal needed for T cell activation
JAK inhibitor	Tofacitinib, baricitinib	Blocks intracellular JAK-STAT cytokine signalling (targeted synthetic DMARD)

Choice of agent is guided by the specific disease, its dominant immunopathological pathway, comorbidities, and prior treatment response/failure - not a fixed universal sequence applied identically to every inflammatory rheumatic disease

Combination therapy (e.g. methotrexate plus a biologic) is common and often more effective than monotherapy in RA specifically, though combination immunosuppression also compounds infection/toxicity risk requiring careful monitoring
Each class carries characteristic toxicity/monitoring requirements (e.g. methotrexate - hepatotoxicity/myelosuppression; biologics - infection risk, requiring the pre-treatment screening detailed in the gastroenterology biologics note; JAK inhibitors - thrombosis and malignancy signal requiring specific risk-benefit discussion, particularly in older or higher cardiovascular risk patients)

Rheumatoid arthritis, psoriatic arthritis, SLE, vasculitis - each with disease-specific preferred agents based on the dominant pathway involved

The expanding range of targeted therapies (biologics and JAK inhibitors) reflects an increasingly precise understanding of which specific cytokine/cell pathway drives each disease - allowing more individualised treatment selection than the older, less targeted conventional synthetic DMARDs alone could offer

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