ProfG suggested a two trials because he though the effect of ocrelizumab on progression could be due to antibody getting into the CNS and suggested a DOuble DOse the Dodo trial. The other trial was a watch an wait so treat for a while and then stop like you would with alemtuzumab and cladribine. This latter study would not be in the interests of pharma as is would a say you can use less drug not more and surprise, surprise there was no interest in this. But the double dose trial was done in relapsing and progressive MS. We tried to get the Watch and Wait trial going but the equipose was lost because many centres were already doing extended dosing. I provided data to support this and at ECTRIMS2025 there is no doubt that extended interval dosing works. The is a UK study looking at intervals suggested with is adaptive to start with a 12 month gap and either go down to 9 monthly or up to 15 monthly. I think we already know and this is reaffirmed in a rituximab trial in the late breaking session as we speak, a 12 month gap is as good as 6 monthly dosing. This however is not a watch and wait but there is a formal trial in the US to address this.
Prof Hauser has just presented data on high dose (1200-1800mg) in the gavotte trial in primary progressive MS so that larger people will get enough antibody. This replicates the Mussette trial in relapsing MS and it shows there is no extra benefit in controlling progression. This does not surprise me because in the original data suggesting the a better effect in smaller people, there was not a proper dose-response effect (as the dose gets higher the benefit gets higher). It rather puts another spanner in the PIRA idea. Here the implication is that these treatments are working on degenerative problems within the CNS. I have argued that this view is flawed and reflects at best a combination of effects in the periphery and blood but much of the effect is due to peripheral activity controlling the immune response typical of relapse driven MS. As such ofatumumab and natalizumab inhibit PIRA…the circulating does of ofatumumab is very low and unlikely to have much direct effect in CNS, could be wrong but the clincher is natalizumab because the mechanism of action is at the blood vessel so outside the CNS.
Source: multiple-sclerosis-research.org