Tysabri® (active ingredient Natalizumab) is a highly effective medication, but it has the significant problem of PML risk – you have already read this statement here quite often. Despite this serious side effect, I advocate that patients who are stable on Natalizumab should not be uncritically discontinued or switched. However, from a medical perspective, there is no question that a change of therapy should be made if a JCV-antibody positive patient expresses fear of a PML and these fears impair his quality of life. A change should be made in a planned manner, and one should switch to a therapy that has a similarly strong clinical effect. It is emerging that Ocrelizumab (Ocrevus ®) could represent an equivalent alternative in terms of its potency. This view is not only based on the study data of Ocrelizumab, but also on the good experiences that have been made with the predecessor substance Rituximab, especially in Sweden, where Rituximab is regularly used for the treatment of MS. Accordingly, the question of switching from Natalizumab to Ocrelizumab is of practical relevance. How should one proceed?
If, even after realistic education about risks and side effects of Natalizumab, there is a desire to change therapy, Natalizumab should be discontinued at an agreed time. Basically, a current MRI should be available at the time of discontinuation, because a main concern when switching to another immunologically active medication is a so-called “carry over” PML. This means that under the previous therapy with Natalizumab the JC virus could already penetrate into the brain and subclinically lead to an infection that is (not yet) noticed – such a carry-over PML has occurred in five patients after switching to Ocrelizumab.
Such a subclinical infection can often be ruled out by careful examination of the MRI images – accordingly, an unremarkable MR when discontinuing Natalizumab is already a reassuring finding. The pause between discontinuing Natalizumab and starting Ocrelizumab should not be too long – a sensible interval is about 6 – 8 weeks, as long as the effect of Natalizumab definitely lasts.
Before starting therapy with Ocrelizumab, there are different recommendations for safety measures. I recommend making another MRI immediately at the start of Ocrelizumab – firstly, because such a baseline finding is required anyway in terms of safety and effectiveness; secondly, because with this image – also in comparison with the one made when discontinuing Natalizumab – I get further reliable indications of a “carry-over” PML. I believe that in the event of complete clinical and MR-tomographic stability, a change can be made without further safety measures.
In the event that the images raise doubts, a lumbar puncture with a JC virus PCR should be performed before starting Ocrelizumab. If this direct virus detection from the cerebrospinal fluid (liquor) is negative, the change can be carried out.
Many colleagues generally recommend performing a lumbar puncture before switching from Natalizumab to Ocrelizumab to increase safety (although it is not 100% even with a negative PCR). I think the patient, who after all has to endure the procedure of lumbar puncture, should be involved in the decision. If the patient values the additional safety provided by the lumbar puncture, then the puncture should be performed in any case.
If you stick to these rules, in my view a change can be made relatively safely.
