Yesterday I was involved in a debate “Anti-CD20 therapies should be used as Immune Reconstitution Therapies rather than maintenance therapies“. I feel that I got a preverbial ass-kicking and the audience favoured keeping the status Quo and treating with anti-CD20….forever.
My take was that the biology and preliminary data is reasonably clear but we need a trial to address the safety and efficacy of this approach…….Will it ever happen? ProfG has his DoDO (Double Dose) trial giving more and more ocrelizumab, so hardly any time to do an ADIOS (Adaptive dosing) study to give less and less.
However, stopping was portrayed as having a fear factor……which is strange given that it is well-known that stopping rituximab and ocrelizumab is not associated with rebound-type disease, associated with stopping migration inhibitors (natalizumab/fingolimod).
First we had a mouse study that is a dogs-breakfast of a paper on so many levels and suggested that repopulating B cells were activated. There was a follow up study in humans which one could also ask questions about the interpretations and how it sits with current knowledge. However, that is too nuianced and people accept the headlines. Anecdote is no antidote for evidence. Maybe I am interptreting data wrong. For example the CRAB drugs are amazing and all made out of stardust
Bovis F, Kalincik T, Lublin F, Cutter G, Malpas C, Horakova D, Havrdova EK, Trojano M, Prat A, Girard M, Duquette P, Onofrj M, Lugaresi A, Izquierdo G, Eichau S, Patti F, Terzi M, Grammond P, Bergamaschi R, Sola P, Ferraro D, Ozakbas S, Iuliano G, Boz C, Hupperts R, Grand’Maison F, Oreja-Guevara C, van Pesch V, Cartechini E, Petersen T, Altintas A, Soysal A, Ramo-Tello C, McCombe P, Turkoglu R, Butzkueven H, Wolinsky JS, Solaro C, Sormani MP. Treatment response score to glatiramer acetate or interferon beta-1a. Neurology. 2020 Oct 6:10.1212/WNL.0000000000010991. doi: 10.1212/WNL.0000000000010991. Epub ahead of print.
Objective: To compare the effectiveness of glatiramer acetate (GA) vs intra-muscular Interferon beta-1a (IFNbeta-1a)), we applied a previously published statistical method, aimed at identifying patients’ profiles associated with efficacy of treatments.
Methods: Data from 2 independent multiple sclerosis datasets, a randomized study (the CombiRx trial, evaluating GA vs IFNbeta-1a and an observational cohort extracted from MSBase, were used to build and validate a treatment response score, regressing annualized relapse rates (ARRs) on a set of baseline predictors.
Results: The overall ARR ratio of GA vs IFNbeta-1a in the CombiRx trial was 0.72. The response score (made up of a linear combination of age, sex, relapses in the previous year, disease duration and EDSS) detected differential response of GA vs IFNbeta-1a: in the trial, patients with the largest benefit from GA vs IFNbeta-1a (lower score quartile) had an ARR ratio of 0.40 (95%confidence interval [CI] = 0.25-0.63), those in the 2 middle quartiles of 0.90 (95% CI = 0.61-1.34) and those in the upper quartile of 1.14 (95%CI = 0.59-2.18) (heterogeneity p = 0.012); this result was validated on MSbase, with the corresponding ARR ratios of 0.58 (95% CI = 0.46-0.72), 0.92 (95% CI = 0.77-1.09) and 1.29 (95% CI = 0.97-1.71); heterogeneity p < 0.0001).
Conclusions: We demonstrate the possibility of a criterion, based on patients’ characteristics, to choose whether to treat with GA or IFNbeta-1a. This result, replicated on an independent real-life cohort, may have implications for clinical decisions in everyday clinical practice.
So a relapse rate of 0.72, so in my mind seven times of what I think should be reasonable….but I wonder if the great and the Good disagree…I am sure they say….GA and beta intererfon are amazing and it is all made out of stardust,