What are the biological drugs used in inflammatory rheumatic disease?

Biological drugs used in inflammatory rheumatic disease

Biological drugs include monoclonal antibodies, fusion proteins and decoy receptors. These are a group of medications which target the specific cytokines, receptors and other cell surface molecules involved in the immune response. They are used as a treatment option in several inflammatory rheumatic diseases.

These biological drugs do not lead to cancer, but the progression of a newly developed cancer, while on these medications, may be accelerated due to the suppressed immune response. Treatment cost is much higher in comparison with another group of anti-rheumatic drugs known as DMARDs. Here is the list of available biological drugs used in inflammatory rheumatic diseases.

Etanercept

Indication: Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), juvenile idiopathic arthritis (JIA)

Mechanism of action: Decoy receptor for TNF-α, i.e. prevent binding TNF to its receptors

Maintenance dose: 50 mg weekly, subcutaneous (SC)

Adverse effects: Increases risk of infection

Contraindications:

• Active infection such as untreated tuberculosis
• Indwelling catheter
• Severe heart failure
• Multiple sclerosis (MS)

Infliximab

Indication: Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), juvenile idiopathic arthritis (JIA)

Mechanism of action: Monoclonal antibody which binds with TNF-α and neutralizes it

Maintenance dose: 3–5 mg/kg 8-weekly, IV

Adverse effects: Increases risk of infection

Contraindications:

• Active infection such as untreated tuberculosis
• Indwelling catheter
• Severe heart failure
• Multiple sclerosis (MS)

Adalimumab

Indication: Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), juvenile idiopathic arthritis (JIA)

Mechanism of action: Monoclonal antibody which binds with TNF-α and neutralizes it

Maintenance dose: 40 mg 2-weekly SC

Adverse effects: Increases risk of infection

Contraindications:

• Active infection such as untreated tuberculosis
• Indwelling catheter
• Severe heart failure
• Multiple sclerosis (MS)

Certolizumab

Indication: Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), juvenile idiopathic arthritis (JIA)

Mechanism of action: Monoclonal antibody which binds with TNF-α and neutralizes it

Maintenance dose: 200 mg 2-weekly SC

Adverse effects: Increases risk of infection

Contraindications:

• Active infection such as untreated tuberculosis
• Indwelling catheter
• Severe heart failure
• Multiple sclerosis (MS)

Golimumab

Indication: Rheumatoid arthritis (RA), Psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), juvenile idiopathic arthritis (JIA)

Mechanism of action: Monoclonal antibody which binds with TNF-α and neutralizes it

Maintenance dose: 50 mg 4-weekly SC

Adverse effects: Increases risk of infection

Contraindications:

• Active infection such as untreated tuberculosis
• Indwelling catheter
• Severe heart failure
• Multiple sclerosis (MS)

Rituximab

Indication: RA, ANCA-positive vasculitis, Off-label in SLE

Mechanism of action: It is an antibody, directed against the CD20 receptor, which is expressed on B lymphocytes and immature plasma cells. It causes profound B-cell lymphopenia for several months due to complement-mediated lysis of cells that express CD20.

Maintenance dose:  2 × 1 g 2 weeks apart IV

Adverse effects: 

• Hypogammaglobulinaemia 
• Infusion reactions
• An increased risk of infections, and
• Rarely, progressive multifocal leukoencephalopathy, a serious and potentially fatal infection of the CNS caused by reactivation of JC virus.

Belimumab

Indication: SLE

Mechanism of action: It is a monoclonal antibody that blocks the effects of the cytokine B-cell-activating factor of the TNF family (BAFF) hence inhibit B-cell activation

Maintenance dose:  10 mg/kg 4-weekly IV

Adverse effects:

• An increased risk of infection
• Leucopenia and
• Infusion reactions.

Abatacept

Indication: RA

Mechanism of action: a fusion protein in which the Fc domain of IgG has been combined with the extracellular domain of CTLA4, which blocks T-cell activation by acting as a decoy for CD28, a co-stimulatory molecule necessary for T-cell activation. In nutshell, it inhibits T-cell activation

Maintenance dose: 125 mg weekly SC or 10 mg/kg 4-weekly IV

Adverse effects:

• Increased risk of infections

Tocilizumab

Indication: RA, JIA

Mechanism of action: monoclonal antibody to the IL-6 receptor

Maintenance dose: 162 mg weekly SC or 8 mg/kg 8-weekly IV

Adverse effects:

• Leucopenia
• Abnormal LFTs
• Hypercholesterolemia
• Hypersensitivity reactions and 
• An increased risk of diverticulitis

Ustekinumab

Indication: PsA

Mechanism of action: antibody to the p40 protein, which is a subunit of IL-23 and IL-12.

Maintenance dose: 45 mg 12-weekly SC

Adverse effects: 

• An increased risk of infections
• Hypersensitivity reactions and 
• An exfoliative dermatitis

Secukinumab

Indication: PsA and AxSpA

Mechanism of action: monoclonal antibody to IL-17A

Maintenance dose: 150 mg 4-weekly SC

Adverse effects: 

• An increased risk of infections
• Nasopharyngitis and 
• Headache.

Anakinra

Indication: RA, Cryopirin-associated periodic syndromes (CAPS), Adult-onset Still’s disease (AOSD)

Mechanism of action: decoy receptor for IL-1

Maintenance dose: 100 mg daily SC

Adverse effects: 

• Increased risk of infections 
• Hypersensitivity reactions and 
• Neutropenia

Canakinumab

Indication: systemic JIA (Still’s disease), AOSD, familial fever syndromes, acute flares of gout resistant to other treatments and CAPS

Mechanism of action: monoclonal antibody directed against the pro-inflammatory cytokine IL-1β

Maintenance dose: 150 mg or 2 mg/kg 8-weekly SC

Adverse effects: 

• Increased risk of infections 
• Hypersensitivity reactions and 
• Neutropenia

For easy remembering the mechanism of action of each biological drugs look at the image below ( Figure no: 24.15 from Davidson's Principles and Practice of Medicine 23rd Edition)

[Targets for biologic therapies in inflammatory rheumatic diseases. Biologic treatments for inflammatory rheumatic diseases work by targeting key cytokines and other molecules involved in regulating the immune response.  (BAFF = B-cell-activating factor of the TNF family; CD = cluster of differentiation; IL = interleukin; TNF-α = tumour necrosis factor-alpha; TNFi = inhibitor of tumour necrosis factor)]

Source: 

• Davidson's Principles and Practice of Medicine 23rd Edition; page: 1006