Infectious complications of disease modifying therapies in MS: An audit of high efficacy therapies pre-treatment screening and risk mitigation

MS Specialists MasterClass 6, 2019
This project was the winner of the MS Academy MasterClass Project Award

Background

There is no gold standard for baseline screening and risk mitigation of infectious complications prior to initiating multiple sclerosis (MS) disease modifying therapies (DMTs). Baseline screening is often based on recommendations from the summary of product characteristics (SPC). These recommendations are based on adverse effects reported during clinical trials, often excluding known class adverse effects that have been reported in other disease areas. Clinical trials involve a finite number of patients over an average period of 24 months and patients with known risk factors are often excluded from participating in clinical trials, consequently some serious adverse effects are only identified during real world practice. Any new risks identified during post marketing authorisation pharmacovigilance are added to the SPC as they become known.

In 2018 the local MS and infectious diseases (ID) teams agreed on the following standards for baseline infection screening prior to starting high efficacy DMTs in MS:

• A standard set of tests: HBV screening (including core antibody) HCV Ab, VZV IgG, HIV Ab/ Ag, HSV IgG, CMV IgG and TB Elispot IGRA. The recommendations were based on known risks and risks that can be predicted from mechanisms of action of DMTs. It is acknowledged that not all of the high efficacy DMTs carry the same level of risk for the above infections, however standardising tests makes it more likely that infection screening will be performed consistently. Moreover screening for multiple infections regardless of planned treatment aids decision making during treatment switching.
• Immunisation prior to initiating long term immunosuppression with ocrelizumab for those with incomplete immunisation records: Check MMR IgG and VZV IgG serology, immunise with DTP, MenACWY, Pneumococcal 23 valent, Hib, influenza and Men B vaccines

JCV/ PML risk stratification in natalizumab treated patients is out of the scope of this report.

Objectives

To evaluate infection screening and risk mitigation of infectious complications prior to initiating high efficacy DMTs. This will in turn aid development of pre-treatment check lists, clinical guidelines and patient information leaflets for immunotherapy in MS.

Method

An audit of baseline infection screening to determine pre – alemtuzumab, cladribine, fingolimod, natalizumab and ocrelizumab screening compliance with the new standards was undertaken. Data was obtained from available electronic records and included: HBV screening (including core Ab), HCV Ab, VZV IgG, HIV Ab/ Ag, HSV IgG, CMV IgG, TB Elispot IGRA and risk mitigation strategies. The following exclusion criteria were used: Treatment initiated during clinical trials, treatment initiated by another MS centre and incomplete electronic records from local district general hospitals or out of area.

Results

A total of 83 records were included. Baseline screening records from January 2015 to November 2018 (n=65) were compared with records for December 2018 to April 2019 (n=18)

In the January 2015 to November 2018 group pre-treatment screening rates were: 62% for HBV screen, 62 % for HCV Ab, 94% for VZV IgG, 69% for HIV Ab/ Ag, 0% for HSV IgG, 0.2% for CMV IgG and 49% for TB Elispot IGRA. These baseline tests complied with SPC recommendations at the time of screening.

The December 2018 to April 2019 group achieved a 100% compliance rate for HBV screen, HCV Ab, VZV IgG, HIV Ab/ Ag, HSV IgG and CMV IgG screening along with an 88 % compliance rate for TB Elispot IGRA testing.

Complete vaccine status check lists were not available to audit from clinical electronic records. Measles IgG, Mumps IgG and Rubella IgG screening was completed on the two occasions when immunisation records were not available.

2 cases of latent TB (pre-ocrelizumab/ natalizumab) were treated with isoniazid 300mg

6 cases of HSV and 4 CMV IgG positive cases were identified.

Multiple positive viral screening tests identified in one case could be attributed to antibody and immunoglobulin acquisition from prior IVIg infusion.

Conclusion:

Infection screening was more complete following implementation of new standards. Pre- treatment screening checklists that are integrated with the electronic patient record will help ensure consistency. Going forward, collaboration between MS specialists and other specialties such as infectious diseases to develop a toolkit and a consensus statement on managing infection risks associated with MS DMTs will improve the care quality of care for people on MS DMTs.