Audit MS Masterclass, Sheffield, 31 st March 2017 Education around PML risk and monitoring at NHNN Queen Square MS Centre UCL Institute of Neurology Queen Square Multiple Sclerosis Centre National Hospital for Neurology and Neurosurgery, London Dr Cristina Marcoci c.marcoci@ucl.ac.uk Honorary Clinical Research Associate
129 MS Patients on Natalizumab treatment March 2017 35% 33.07% 30% 25% 1-12 infusions 13-24 infusions 20% 15% 10% 7.09% 14.96% 12.60% 8.66% 15.75% 7.87% 25-36 infusions 37-48 infusions 49-60 infusions 61-72 infusions >72 infusions 5% 0% Patients exposed
Blood tests Natalizumab-Treated Patients Monitoring HCG pregnancy tests (prior to infusion) Blood tests (every 3 months in clinic) Positive Negative Haemolysed YES NO Immediate treatment discontinuation Repeat blood test prior to next infusion
Natalizumab-Treated Patients - PML Risk Monitoring Anti-JCV Antibody Testing Brain Anti-JCV Antibody Status Positive Negative Treatment duration < 21 months Treatment duration > 21 months Annually brain Anti-JCV antibody testing every 6 months Annually brain Anti-JCV antibody testing every 6 months Every 3 months brain Anti-JCV antibody testing every 6 months PML surveillance protocol (from 1 st July 2016)
Anti-JCV Antibody Testing Patients Monitoring (n=129) Re-testing of anti-jcv antibody every 6 months 60% 50% 40% 57% 55% 43% 45% 30% 20% Anti-JCV Negative Anti-JCV Positive 10% 0% July-December 2016 January 2017
Anti-JCV Antibody Testing PML Risk Monitoring Changed serostatus (from July - December 2016 to January 2017) Positive Negative 3% Negative Positive 5% Anti-JCV antibody positive patients (n=58) (March 2017) Antibody index 0.9 Antibody index > 0.9. Antibody index > 1.5 42.31% 7.69% 50%
PML Risk estimates (129 patients) March 2017 50.0% 45.0% 45.6% 40.0% 35.0% 30.0% 25.0% 20.0% 15.0% 10.0% 5.0% 0.0% 11.2% 12.0% 5.6% 6.4% 4.8% 2.4% 2.4% 1.6% 1.6% 1.6% 2.4% 2.4% 0.1 0.2 0.4 0.5 0.6 0.9 2 3 5 6 7 8 10 PML risk estimates per 1,000 patients
Patient 1 QSD01XXX Male, 55 years of age Onset of MS: 1999 First DMT Avonex Commenced on Natalizumab 23/11/2010 (overall 72 infusions) Anti-JCV positive ANTI-JCV ANTIBODY STATUS (2012-2017) JCV stratify Unilab Denmark No NHS consts POS 0.635 0.741 0.44 0.29 NEG
Patient 1 Male, 55 years of age Day care 1.5 2.5 hours stay Infusions / scans (March 2016-2017) 61 62 63 64 65 * 66 67 68 69 * 70 71 * 72 09-Mar-2016 05-Apr-2016 26-Apr-2016 03-May-2016 08-Jun-2016 11-Jul-2016 16-Aug-2016 25-Aug--2016 30-Sep-2016 01-Nov-2016 30-Nov-2016 02-Dec-2016 30-Dec-2016 17-Jan--2017 09-Feb-2017 10-Mar-2017 14-Mar-2017 20-Mar-2017 scans 7-900 12 infusions - 13,560 NHS costs, 14,460 Deferred Unknown reason Deferred Patient did not attend Deferred not reported in time
Patient 2 4041XXXX Male, 44 years of age Onset of MS: 2006 First DMT Rebif 44 mcg Commenced on Natalizumab 20/11/2009 (overall 93 infusions) Anti-JCV positive ANTI-JCV ANTIBODY STATUS (2012-2017) JCV stratify Unilab Denmark No NHS consts POS 0.741 POS 2.84
Patient 2 Male, 44 years of age Day care 1.5 2.5 hours stay Infusions / scans (March 2016-2017) 81 82 83 84 85 86 87 88 89 90 91 92 93 23-Mar-2016 22-Apr-2016 30-Apr-2016 20-May-2016 16-Jun-2016 15-Jul-2016 11-Aug-2016 26-Aug-2016 12-Sep-2016 14-Oct-2016 18-Nov-2016 05-Dec-2016 09-Dec-2016 05-Jan--2017 02-Feb-2017 18-Feb-2017 20-Mar-2017 scans, - 1,200 13 infusions - 14,690 NHS costs, 9 15,890
Patient 3 4039XXXX Female, 52 years of age Onset of MS: 2009 First DMT Rebif 44 mcg Commenced on Natalizumab 28/02/2011 (overall 75 infusions) Anti-JCV negative ANTI-JCV ANTIBODY STATUS (2012-2017) NEG NEG NEG NEG NEG NEG NEG NEG JCV stratify Unilab Denmark No NHS consts
Patient 3 Female, 52 years of age Day care 1.5 2.5 hours stay Infusions / scans (March 2016-2017) 63 64 65 66 67 68 69 70 71 72 73 74 75 23-Mar-2016 22-Apr-2016 20-May-2016 16-Jun-2016 25-Jul-2016 25-Aug-2016 23-Sep-2016 10-Oct-2016 21-Oct-2016 23-Nov-2016 19-Dec-2016 19-Jan--2017 17-Feb-2017 17-Mar-2017 scan - 300 13 infusions - 14,690 NHS costs,9 14,990
Patient 4 4000XXXX Male, 28 years of age Onset of MS: 2006 First DMT Rebif 44 mcg Commenced on Natalizumab 01/11/2010 (overall 76 infusions) Anti-JCV negative ANTI-JCV ANTIBODY STATUS (2012-2017) NEG NEG NEG NEG NEG NEG NEG NEG JCV stratify Unilab Denmark No NHS consts
Patient 4 Male, 28 years of age Day care 1.5 2.5 hours stay Infusions / scans (March 2016-2017) 63 64 65 66 67 68 69 70 71 72 73 74 75 76 04-Mar-2016 01-Apr-2016 28-Apr-2016 27-May-2016 23-Jun-2016 22-Jul-2016 25-Jun-2016 23-Aug-2016 19-Sep-2016 17-Oct-2016 25-Oct-2016 14-Nov-2016 18-Nov-2016 12-Dec-2016 09-Jan--2017 07-Feb-2017 10-Mar-2017 scans 7-900 14 infusions - 15,820 NHS costs, 16,720
Patient 5 4075XXXX Female, 28 years of age Onset of MS: 2007 First DMT Copaxone Commenced on Natalizumab 2008 (overall 97 infusions) Anti-JCV positive JCV stratify Unilab Denmark No NHS consts ANTI-JCV ANTIBODY STATUS (2012-2017) POS 1.4 0.59 NEG NEG NEG NEG
Patient 5 Female, 28 years of age Day care 1.5 2.5 hours stay Infusions / scans (March 2016-2017) 85 86 87 88 89 90 91 92 93 94 95 96 97 23-Mar-2016 22-Apr-2016 17-May-2016 14-Jun-2016 16-Jul-2016 12-Jul-2016 08-Aug-2016 13-Sep-2016 11-Oct-2016 11-Oct-2016 08-Nov-2016 06-Dec-2016 03-Jan--2017 31-Jan-2017 12-Feb-2016 02-Mar-2017 scans 7-900 13 infusions - 14,690 NHS costs, 14,990
Conclusions At NHNN Queen Square MS Centre: Patients are educated about PML risk by a well-organized team; A continuous monitoring of PML risk is proved to be on a high level and according to required standards; From the 1 st of July 2016 a new PML surveillance protocol was approved and is applicable to Anti-JCV positive patients who have been on Natalizumab treatment for more than 21 months ( scans: currently every 3 months; previously every 6 months); Anti-JCV Antibody tests are performed every 6 months; Overall, during a period of time March 2016 March 2017, based on the examples of five MS Natalizumab-treated patients, NHS paid approximately 76,950 77,050.
Acknowledgements Prof Kenneth Smith Dr Martin Duddy Dr Waqar Rashid Prof Olga Ciccarelli Margaret Vincent Pinar Kara
Thank you very much for your attention!