Switching-2- Natalizumab

Natalizumab: Recent data has shown that reducing the dosing interval between Nz infusions (extended interval dosing or EID) will lower the risk of someone developing PML. Whether receiving Nz every 5 or 6 weeks remains as effective as every 4 weeks in unknown.

Restarting Natalizumab: Before restarting Nz it is important to do the routine bloods, a baseline MRI and check for anti-Nz antibodies. MSers who stop Nz may develop anti-natalizumab antibodies that put them at risk of developing infusion reactions. The presence of these antibodies is a contraindication to restarting Nz. It is not uncommon for MSers to request being switched back to Nz after switching to another DMT. Nz is known to reduce MS-related fatigue and cog-fog and this often returns when it washes out. The ability to reduce PML risk with EID may increase the number of MSers requesting to go back onto Nz, to help manage these symptoms.

Other DMTs: In general there are no DMTs that natalizumab cannot be used afterwards provided the baseline screening bloods are okay and there are no specific contraindications to the specific DMT concerned. There are some specific caveats highlighted below.

Interferon-beta and glatiramer acetate: I have no concerns and would not recommend any specific washout period between stopping either IFN-beta or GA.

Non-selective cell depleting DMTs (alemtuzumab & HSCT): I assume that you would be wanting to start Nz after alemtuzumab or HSCT because of recurrent disease activity. If this is the case I would start natalizumab as soon as possible. Please note as alemtuzumab and HSCT are immunosuppressive therapies they will make any MSer who is JCV seropositive at high risk of developing PML and will render the so called anti-JCV index unreliable. If your MS is not active post-alemtuzumab or HSCT I would question the need for Nz as both these DMTs can induce long-term remission.

Selective cell depleting DMTs (cladribine and ocrelizumab): I assume that you would be wanting to start Nz after cladribine or ocrelizumab because of recurrent disease activity. If this is the case I would start Nz as soon as possible. Please note as cladribine and ocrelizumab are immunosuppressive therapies they will make any MSer who is JCV seropositive at high risk of developing PML and will render the so called anti-JCV index unreliable. If your MS is not active post-cladribine or ocrelizumab I would question the need for Nz as both these DMTs can induce long-term remission; ocrelizumab included. The data supporting the latter has yet to published.

Fingolimod: No fingolimod washout period is required when switching to Nz. However, if someone has an infectious complication, particularly a CNS infection, then it would be ill advised to start Nz until the CNS infection has been cleared. Nz will prevent lymphocyte trafficking into the CNS and hence will blunt the immune response to the infectious agent.

Dimethyl fumarate: No DMF washout period is required when switching to Nz. The same warning about CNS infections applies to DMF as to mentioned above.

Teriflunomide: No teriflunomide washout period is required when switching to Nz. However, if the reason for the switch to Nz is to allow MS disease control so that an MSer can fall pregnant, then the MSer will need to undergo rapid teriflunomide elimination because of its long half-life and potential for teratogenicity.

Special circumstances: The presence of specific comorbidities and adverse events may make it difficult to start Nz after certain DMTs. These are, however, uncommon in routine clinical practice.