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 medication 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 are the 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 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 leucoencephalopathy, 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 inhibit 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 nflammatory 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

Post a Comment

0 Comments