Biologics & Biosimilars
Biologic and novel therapies have been a major advance in the management of many inflammatory conditions in both adults and children. They are called ‘cytokine modulators’ or ‘biologics’ and block selectively the effects of pro-inflammatory cytokines. Patients and families will need advice and information about the treatment plan, counselled about side effects, long term impact of treatment and formal consent maybe required. The nurse will also need to provide teaching and training on how to administer the medication at home where appropriate.
The Royal College of Nursing (RCN) have produced a competency and role development framework - for rheumatology nurse specialists and all other nurses working with rheumatology patients. This framework can be used to 'bench mark' services, support individual personal development plans (PDP) and continuous professional development (CPD). It can be used alongside previous competences and guidelines including prescribing, assessing and monitoring biologic therapies and subcutaneous methotrexate.
- Baseline investigations are required before starting treatment and include excluding infection such as Tuberculosis (blood test/chest x-ray), immune status (varicella, measles, rubella).
- Regular blood tests are required to monitor efficacy and safety.
- Vigilance regarding infection is important, especially as the classical symptoms and signs may not be apparent, and urgent referral is warranted if infection is suspected.
- Patients and families need to know to avoid live vaccines and pregnancy when on MTX or biologics and other immunosuppressives, especially if also on systemic corticosteroids.
- Families need to know when to seek prompt medical care if the child is unwell.
- Varicella vaccination should be considered in all patients with incident JIA who are non-immune and before immunosuppression is started.
- In the young adult or adolescent taking MTX, education about contraception and avoidance of excessive alcohol consumption is essential.
- There are NICE guidelines for the use of biologics in JIA.
- In the UK there is guidance for the sequential use of biologics in JIA.
- Many biologic therapies have dramatic impact on disease control and evidence shows sustained improvement. Clinical trials are important to establish efficacy and safety but there are concerns about infection risk, impact on fertility and malignancy risk. Monitoring of real life use of biologics is important and there are Registries and cohort studies in progress.
- The emergence of biosimilars is likely to result in lower costs and therefore improve access to effective treatments for more children although there are concerns about safety and efficacy.
- For those few children with severe refractory disease failing to respond to biologics, a further option is T-cell depletion coupled with autologous haematopoietic stem-cell rescue albeit this is limited to specialist centres and needs careful selection of patients.
The number and variety of these treatments is expanding rapidly but currently includes:
- Tumour Necrosis Factor-α Inhibitors: Etanercept (Enbrel®), Infliximab (Remicade®), and Adalimumab (Humira®) are widely used in the treatment of several different rheumatic diseases of childhood. They have been associated with severe infections, especially Tuberculosis and septicaemia. Effects last for at least 3 months after stopping.
- Interleukin-1 Inhibitors: Anakinra (Kineret®), Rilonacept, and Canakinumab are used in Systemic-Onset Juvenile Idiopathic Arthritis (S0JIA) and a number of Auto-inflammatory syndromes. They are highly effective treatments but as part of their actions may suppress many signs of infection (fever, raised CRP etc). Effects last for at least 3 months after stopping.
- Interleukin-6 Inhibitors: Tocilizumab (Ro-Actemra®) is used in Systemic-Onset JIA. It has been associated with serious, even fatal, infections and like IL-1 inhibitors may effectively mask signs of infection such as fever and CRP. Effects last for at least 3 months after stopping.
- T-Cell Co-Stimulatory blockers: Abatacept (Orencia®) is used in JIA. It blocks the interaction between T-cells and Antigen-presenting cells. Effects last for at least 3 months after stopping.
- B-Cell inhibitors – Rituximab (Mabthera®) acts by killing mature B-cells to prevent antibody production for up to 18 months.
|Cytokine modulators in use to treat rheumatic disease
||Mechanism of action
||Route of administration
||Important issues for the child taking cytokine modulators and apply to all cytokine modulators
||TNF-α soluble receptor that binds to circulating TNF and competes with membrane receptor.
||Subcutaneous injection twice a week.
|| Avoid live viral vaccines.Promote annual flu vaccine.Promote pneumococcal immunization (current advice 5-yearly).Vigilance regarding infections (e.g., varicella and herpes zoster, Tuberculosis, opportunistic infections such as listeriosis).Advice regarding travel abroad with medicines and travel insurance.
||Human–murine chimeric antibody that neutralizes TNF-α.
||Intravenous infusion. Various regimens, initially every 2 weeks and then every 4–8 weeks.
||Fully human monoclonal antibody neutralizes TNF-α.
||Subcutaneous injection fortnightly.
|| IL-1 receptor antagonists.
||Subcutaneous injection (daily – anakinra, fortnightly rilonacept, Monthly canakinumab.
||Anti B cell therapy.
|| Intravenous injection given 6 to 12 monthly.
||IL-6 receptor antagonist.
||Intravenous infusion fortnightly or monthly.
||CTLA4-antagonist to block T cell and B cell interaction and initiation of the pro-inflammatory pathway.
||Given by monthly infusion.