25th February 2025

Biologics

Overview of biologics

Biological disease-modifying anti-rheumatic drugs are proteins which are derived from human genes and genetically engineered to inhibit specific parts of the immune system. There are four main inflammatory targets: tumour necrosis factor (TNF) inhibitors (most common), B cell inhibitors, interleukin inhibitors and T cell inhibitors.

They are more precise and rapid-acting than conventional DMARDs, which have a broad immune-suppressing effect. However, they are more expensive, so are only used after these (often 2 options) have failed to work and as per NICE criteria. They are often given with methotrexate to reduce loss of efficacy from anti-drug antibody formation.

As with conventional DMARDs, there are a variety of side effects. In general, these include: an increased risk of infection (active bacterial or severe viral infection is a contraindication), blood dyscrasia, gastrointestinal upset, fatigue, myalgia and headaches. There has been debate about risk of malignancy (current is a contraindication), but evidence only suggests an increased risk of skin cancers, particularly melanoma, with TNF inhibitors.

Specific biologics and side effects

Table 3 Examples of different sub-classes of biologic, their uses, route of administration and side effects
*TNF inhibitors should not be prescribed in those with multiple sclerosis or severe heart failure (NYHA grade 3-4)
**Mainly with infliximab and adalimumab

Monitoring of biologics

In general, monitoring requirements are:

• At baseline: FBC, U&Es, LFTs, CRP, ESR, lipids, HIV, hepatitis B and C, urinalysis (for protein), blood pressure and CXR with QuantiFERON for TB
• Patients should be treated if found to have latent TB
• FBC, U&Es and LFTs at 3-4 months, then every 6 months
• Lipid profile at 1-2 months
• Rituximab may also need Igs and CD19 monitoring 6 monthly 
• Further infection screens, if clinically indicated 

Patients should be offered vaccinations before starting treatment: influenza, pneumococcal and covid. Live vaccinations should be avoided. Education should be given about skin cancer prevention and infection risk.

There are guidelines for use in pregnancy and breastfeeding, but little data.

References

• National Institute for Health and Clinical Excellence. DMARDs [Internet]. NICE. 2021 [cited 2022 July 27]. Available from: https://cks.nice.org.uk/topics/dmards/ 
• Kumar, P. J., & Clark, M. L. (2002). Kumar & Clark clinical medicine. Edinburgh, Saunders
• Clunie, Gavin and others (eds), Oxford Handbook of Rheumatology, 4 edn, Oxford Medical Handbooks (Oxford, 2018; online edn, Oxford Academic, 1 July 2018)
• Joint Formulary Committee. British National Formulary. Edition 83 ed. London: BMJ Group and Pharmaceutical Press; 2022