Karen Topping discusses the complexities of immunoglobulin usage and how current demand cannot be met
Human normal immunoglobulin (Ig) is currently available in the UK from eight different manufacturers in both subcutaneous and intravenous forms. NHS England commissions Ig usage based on the Department of Health’s 2008 guidelines.1
A colour-coded prioritisation scheme is in place, which ensures that patients with the most severe, life-threatening conditions receive Ig as a priority. The guidelines suggest a variety of dosage regimens for patients, and treatment may be acute or long term.
Around 16,000 patients are treated with Ig annually.2 Neurological conditions use the most Ig by volume (44%), immunology uses 32%, and haematology uses 9%. Other specialities that use Ig include paediatrics, transplant, dermatology, intensive care, infectious diseases, and obstetrics. The most common indication for Ig usage is primary immunodeficiency disease, followed by secondary antibody deficiency, and thirdly, immune thrombocytopenia.2 See Box 1 for further information on Ig therapy.
Managing the governance around Ig within NHS trusts is a complex task, particularly because unlike most high-cost drugs, Ig is not restricted to a few speciality areas. Trusts are required to submit Ig usage reports (including indication, volume received, and outcome data) to NHS England on a quarterly basis via the National Immunoglobulin Database.4 Trusts are also required to have an immunoglobulin assessment panel (IAP) in place to oversee the governance of Ig, consisting of prescribers and pharmacists experienced in Ig usage.
NHS England was expected to spend £200 million on Ig products in 2017/18, and sales to NHS trusts increase by approximately 10% each year.2 A national demand management programme is in place under the direction by the Commercial Medicines Unit (CMU) and trusts are allocated an annual volume of Ig based on the previous year’s usage and forecasted growth.
Unfortunately, given trust forecasted usage, sales figures, and Ig manufacturing levels, the current demand for Ig cannot be met. For the first time, managing Ig usage based on what is available in the market is a priority, as the previous strategies adopted by Ig prescribers of reducing usage are no longer sufficient.
NHS England needs to ensure that patients with the most severe and life threatening conditions can continue to receive Ig, and hospital trusts must now work with NHS England and the CMU to reduce their planned Ig usage even further. Action is required immediately and it will require tough decisions. Patients, commissioners, IAPs, and clinical teams must work together to achieve this.
Box 1: What is immunoglobulin?
Human normal immunoglobulin is a sterile preparation of concentrated antibodies derived from the blood plasma of immune individuals.3 When injected, it can provide immediate protection against certain infective organisms, such as hepatitis and measles. This ‘passive immunity’ can last for several weeks.3
Ig preparations were first used in the 1950s as replacement therapy in primary immunodeficiency disorders. Around 30 years ago, suspensions of Ig suitable for intravenous use became available (IVIg). The ability to administer large quantities of Ig intravenously means that IVIg is now an important treatment option in a number of clinical indications beyond primary immunodeficiency, including autoimmune and acute inflammatory conditions, and off-label prescribing occurs in almost every medical specialty.1
UK market issues
The instability of the UK market is a long-standing issue for several reasons:
- long-standing production issues from companies, including withdrawal from the UK market
- limited appeal of the low pricing of the UK market
- increased demand internationally
- the UK is unable to contribute plasma due to the Creutzfeldt-Jakob Disease (CJD) risk.
Previous strategies employed by NHS England to reduce Ig usage have included:
- prioritise Ig to treatment of red and blue indications (i.e. those conditions with the highest risk to life and the most evidence of effectiveness)
- ensure adherence to national guidelines for Ig usage, including review of local guidelines
- monitor trust submission of Ig patient outcome data on the National Immunoglobulin Database
- communicate market position of manufacturers of Ig to trusts, in terms of their ability to meet demand.
Strategies employed by trusts to reduce Ig usage include:
- review appropriateness, dose, and frequency of immunoglobulin in existing patients
- consider other clinically effective and cost-effective treatment options for all patients who are considered for or receiving Ig treatment (e.g. trial of steroids or plasma exchange)
- ensure IAP engagement and submission of outcome data on the National Immunoglobulin Database
- put in place a mechanism for review of urgent Ig requests (e.g. medical director approval).
Action is required immediately… patients, commissioners, IAPs, and clinical teams must work together
In recognition of the challenge of managing the ongoing demand for Ig, NHS England has established new priorities:
- implement sub-regional IAPs to improve clinical stewardship in defined geographical areas
- update national clinical guidelines in line with evidence-based outcome data
- ensure Ig allocation is reviewed regularly, minimising effect on patients
- update Commissioning for Quality and Innovation (CQUIN) for medicines optimisation.
Throughout what will be a challenging time, it is imperative that the impact on patient care is minimised. NHS England and clinical teams must engage with patients to reassure them that they are working to minimise effects on their care and ensure there are no interruptions to their treatment. Patients must be involved in any discussions regarding dosage regimen changes and brand switching that are made.
1. Department of Health. Clinical guidelines for immunoglobulin use. Second edition, 2008. Available at: assets.publishing.service.gov. uk/government/uploads/system/uploads/attachment_data/file/216672/dh_130393.pdf
2. NHS. MDSAS. Immunoglobulin database annual report 2016/17. Available at: igd.mdsas.com/wp-content/uploads/ImmunoglobulinDatabaseReport201617.pdf
3. British National Formulary. Immunoglobulins. bnf.nice.org.uk/treatment- summary/immunoglobulins.html (Accessed 15 November 2018)
4. NHS England. National demand management programme for immunoglobulin. The National Immunoglobulin Database. igd.mdsas.com/ig-database/ (Accessed 15 November 2018)