Audit of safe monitoring of MS patients on natalizumab

Natalizumab is a monoclonal antibody which is one of the most effective treatments for relapsing remitting MS. Although the treatment is relatively safe, one complication of therapy is the development of progressive multifocal leukoencephalopathy (PML), if a patient becomes infected with JC virus (JCV), which can be disabling or fatal.

As natalizumab is becoming used more frequently, it is important that when a patient is started on therapy that they are monitored for signs of PML and for evidence of developing positivity for the JC virus. This is usually done through regular brain imaging and blood JC virus serology testing.

Reasoning for audit

Sheffield Teaching Hospitals NHS Trust provides neurological services to a large area of the north of England with a catchment population of over 2.5 million patients. Sheffield is the site of the South Yorkshire MS specialist clinic and research facility. Natalizumab treatment is often used in our institution for the treatment of MS. Prior to this audit being performed an initial audit in 2015 had found that over 50% of patients had not had their JC virus status checked for over 12 months, less than 25% of patient had MRIs performed yearly, methods for recording JC virus positivity where rudimentary and not easily accessible, and no consensus existed on how natalizumab patients should be monitored.

As a result, guidelines were put in place for regular MRI imaging, the frequency of which was tailored to the risk of PML, informed by JC virus index, length of time on treatment, and prior immunosuppression. We also worked with the informatics and microbiology team to allow JC virus results to be easily accessible on the electronic results system.

A major shift in our thinking was that instead of medical staff arranging these investigations the role was moved to nursing staff who administer natalizumab infusion in a neurology day care setting.

This audit was performed to investigate if these changes in JC virus monitoring improved compliance with national guidance.

Methods

A notes-based audit was performed on the notes of all patients receiving natalizumab at Sheffield Teaching Hospitals. The following audit standards where assessed:

• JCV STATUS
  • If JCV <1.5 or negative, patients undergo JCV testing every six months (±2 months)
• MRI SCANNING
  • All patients receiving nataluzimab are scanned at least yearly (±2 months)
  • Those who are JCV positive with a titre <1.5 AND on natalizumab for >2 years; are being scanned every six months (±2 months)
  • Those who are JCV positive with titre >1.5 AND on natalizumab for >2 years; are being scanned every four months (±2 months).

Results

In total 161 patient notes where audited, six patients had stopped treatment with nataluzimab at the time of the audit and so only 155 where included in this analysis. Twenty-six patients had only started natalizumab treatment within the last six months so where excluded from the JCV status analysis.

The results of the audit where as follows:

• JCV STATUS
  • If JCV <1.5 or negative, patients undergo JCV testing every six months (±2 months)
    • 128 out of 129 patients (99.2%) had appropriate testing
    • One patient did not have testing at 11 months and was unable to come prior to this due to geographical reasons.
• MRI SCANNING
  • All patients receiving natalizumab are scanned at least yearly (±2 months)
    • 148 patients had MRI with interval less than 14 months (95%)
    • Five patients had MRI with interval between 15-16 months (3%)
    • One patient had only one MRI with future MRI planned. (Previous MRI done in Greece) (0.6%)
    • One patient had an MRI interval of 36 months but other MRIs were done in in Newcastle (0.6%)
    • One patient had MRI interval of 39 months (claustrophobic and requires GA) (0.6%)
  • Those who are JCV positive with a titre <1.5 AND on natalizumab for >2 years; are being scanned every six months (±2 months)
    • 22 patients where JCV positive with a titre less than 1.5
    • 20 patients had MRI with interval between 3-8 months (90.9%)
    • Two patients who turned positive recently had a previous MRI 11 months ago (9%)
  • Those who are JCV positive with titre >1.5 AND on natalizumab for >2 years; are being scanned every four months (±2 months)
    • 15 patients where JCV positive with a titre greater than 1.5
    • 100% scanned at three to five month intervals

Conclusions

By introducing a standardised nurse-led method by which MRI scans and JCV serology is monitored we have managed improve to almost a 100% compliance all our standard monitoring for patients who are undergoing treatment with natalizumab. Although with initial resistance from nursing staff at taking on this responsibility we have shown that in this particular situation nurse-led assessment of JCV status has improved the safety of patients undergoing natalizumab therapy. At a more recent feedback exercise nursing staff mentioned that they appreciate the increased autonomy and being able to help with patient care.

Recommendations

• Standardising safety monitoring when treating patients with natalizumab leads to better compliance and better patient care
• Highlighting the needs for monitoring to all staff improves compliance
• Increasing ease of access to serology results helps in the monitoring of JCV levels.
• Including nursing staff in the role of safety monitoring in natalizumab prescribing can improve compliance with this guidance.

Acknowledgements

Drs Paling, Hosty, Kass-lliyya, and Bell would like to thank all the neurology day case staff at the Royal Hallamshire hospital for participating in this audit.