#080: B-Cell Depletion – Ocrelizumab (Ocrevus), Ofatumumab (Kesimpta, Bonspri), Rituximab (Mabthera, Rituxan), Ublituximab (Briumvi) for active RRMS and SPMS, and early PPMS

To get a good overview of the major topic of therapy decisions, I recommend that you first listen to episode 58: Immunotherapy in MS. A guide to efficacy and choice with Prof. Tjalf Ziemssen. There you will find out why:

• You can only compare the various disease-modifying drugs to a limited extent.
• It is important to start an effective therapy quickly.
• MRI and other examinations are important for assessing progression and provide information about effectiveness.
• Therapies should be changed as little as possible, but of course if they are not effective enough.
• In most cases, it is better to start with a highly effective therapy and only switch to a lower category at an advanced age.
• In the case of highly active MS, it may be more important to start immunotherapy quickly and tackle rehabilitation as a second step.
• Generics and biosimilars are being used more and more and which approval requirements they have to fulfill.
• The risks and side effects of a therapy must be differentiated into unpleasant side effects at the start of therapy and rare possible risks. And these must be set in relation to the usually irreversible effects of untreated MS in the long term.
• It is important to honestly discuss your opinion, wishes, goals and fears with your neurologist in order to make treatment decisions together that both sides can agree on.
• It is advantageous to be cared for by MS specialists and to stay informed yourself in order to benefit from new findings and treatment options.
• Contribute to a favorable prognosis with your own healthy lifestyle.

Another general note

The approval studies for the individual drugs were carried out at very different times. Thirty years ago, you had to be more severely affected or more advanced in the course of the disease to receive a reliable diagnosis of multiple sclerosis. Less severely affected people were probably not diagnosed or not diagnosed at first. With ever-improving examination methods, such as MRI, even small lesions in the central nervous system can now be seen better. Furthermore, 30 years ago it was not yet known that neuromyelitis optica spectrum diseases, NMOSD for short and MOGAD, are separate diseases that require their own therapies and sometimes even react negatively to MS medication. They were previously thought to be multiple sclerosis and MS therapies did not alleviate the disease activity.

Ocrelizumab is approved for the treatment of active forms of RRMS and early primary progressive MS (PPMS). The Multiple Sclerosis Competence Network (KKNMS) recommends its use in patients who have already received other immunotherapies, but also in therapy-naive patients. It is important to demonstrate disease activity through relapses or in imaging through MRI. The disease activity must have occurred within the last two years.

In the ORATORIO study, PPMS patients aged 18 to 55 years, with an EDSS of 3.0 to 6.5 and a disease duration of less than 10 years (EDSS ≤ 5.0 at screening) or less than 15 years (EDSS > 5.0 at screening) were examined and a benefit was found.

In PPMS patients over 56 years of age, with higher EDSS and/or longer disease duration, a strict risk-benefit assessment must be made. Tolerability and efficacy have been demonstrated in the OPPORTUNITY study.

Anti-CD20 therapies should not be used if you are allergic to the active ingredient or any other components of the medication, or if you currently have a serious infection.

Special precautions are needed for:

• Chronic infections such as HIV or hepatitis B/C, as the therapy could weaken the immune system.
• People who are prone to infections, such as frequent bladder infections or lung infections.
• People with a weak immune system, for example due to cancer or other diseases that affect the immune system.
• Previous cancer – in this case, the treatment should be discussed with the oncologist.
• Pregnancy or breastfeeding: If you had frequent MS relapses before pregnancy, therapy can be resumed during breastfeeding, but ideally not until 1-2 weeks after birth.
• Children and adolescents under 18 years of age, as there is insufficient safety information.

Ocrelizumab: For people with progressive MS for more than 15 years or with a degree of disability above 6.5, it should be carefully considered whether treatment is appropriate.

Ofatumumab and Ublituximab: In people over 55 years of age or with a degree of disability above 5.5, safety and efficacy have not been sufficiently studied. Here, too, the risk should be carefully weighed against the benefit.