Finally, BIIB and ELN get their voice for TY efficacy balanced with risk...
This is a copy of a note I posted on the ELN IVMB.
Finally Publications portray extensive Ty benefits with realistic risk
BIIB and ELN have published 4 articles in the journal "Multiple Sclerosis," which pull together a massive amount of data on Ty benefits from a wide range of post marketing studies, best practices for selecting and managing patient use of TY, and identification of clinical actions to identify at risk patients, minimize exposure, and recover from PML. All told, it is 36 pages of fairly dense statistics and recommendations. Combined reference counts for the 4 articles indicate they have summarized well over a hundred papers, so while much of the material is familiar to the average ELN IVMB member, there is considerable new data... and of course this is all gathered in one place and very well organized. Very useful.
That said, there is a disclaimer I have to make before proceeding. These papers are supplements to the November issue. BIIB and ELN paid for their publication and fees for the open access at the URLs below. BIIB and ELN are upfront about identifying their payment, their funding for development of the papers and the professional editorial polish they present. Since this is a summary of many other works, I am not so troubled, but "Caveat lecter," nonetheless.
I use the brand names rather the scientific nomenclature even within quote marks. Sorry.
The introduction is only six pages and I recommend reading at least that one.
msj.sagepub.com
The first page or two present the statistics behind the loss of QoL that MS patients live with... and the shortened lives they live in comparison to non-MS. With non-Ty treatments, 44% of patients significantly worsen in a decade. In any 20 year period, about 14% die. Grim. Page 3 makes the case that all reported measures actually underestimate the area of the misery curve. Page 4 presents the case for economic loss and employment problems. As grim as these seem, we are aware of them from first hand reports on this board. Their conclusion for this section states, "The benefits of Ty may outweigh the rare risk of PML."
The second article is simply put most remarkable. The authors are Coyle and Jeffery, both published skeptical and occasionally highly negative reviews of Ty in the pre 2005 to 2007 time frame. They champion Ty's efficacy based on published clinical data and patient registry data. msj.sagepub.com
Just hitting the highpoints for my scan, there are lots more nuggets in this paper...
A. Page 1 is very good overarching summary of all MoAs that Ty leverages to achieve its efficacy.
B. Table 1 is Affirm and Sentinel data. Good to review again. What I noticed years ago is how much the data in the column for Avonex looked like the Placebo arm data for Ty.
C. Summary for this section [remember who wrote it], "Overall, AFFIRM results demonstrated impressive efficacy not previously seen in clinical trials of RRMS on all parameters studied."
D. Page S10 provides results from the fabled GLANCE study [Copaxone]. They had data on 110 randomized, double blinded placebo controlled patients. Most measurements were strikingly in favor of Ty and significant. Alas, although Ty had better relapse scores than Copaxone, it was not statsig.
E. They do post hoc stats on highly active MS benefits. Ty wins.
F. As those who tortured the study data were convinced that some patients had to get a lot better, they confirm it. 30% got better. No Disease activity is seen in just under 50% of Ty users. At this stage of medical science, you get better data only with miracles.
G. Italian registry of 908 patients with no previous benefits from the IF-b's showed 49% improved with Ty, 45% stable, and 5% worsened.
H. Danish study reported on had details indicating that about 20% of their population had been on prior Novantrone. They were very sick compared to the 80%. So, perhaps as much as 20% of other Western Europe Ty users had been on Novantrone.
I. Summary: "... all post marketing studies suggest similar efficacy in clinical practice." And, other "DMTs, [IF-b and GA] are suboptimal for at least 30% of patients." "Ty appears to play an important unmet need in the treatment of patients with MS."
Paper 3 is on "Clinical Vigilance..." THis paper clearly went to press befor Ted Yednock's interview and the identificaiton of geographic strains of JCV as a useful identificaiton feature. It provides a good historical overview of its clinical emergence and tie-in with HIV/AIDS. They present a great deal of information on why identification of PML is so difficult. Table 1 on differential diagnosis featurs looks pretty hopeless to me. The test they present for JCV detection has a major problem [I hope it is not the one we read about now]. The specificity is greater than 95%, but the sensitivity varies between 50% and 90%. "A defnitive PML diagnosis can be made with a brain biopsy." [page S19] Good description of potential treatments and the list of potential medications is longer than I would have thought. Many have obviously been tried with some level of success. 3 summary paragraphs on counseling patients on risk, minimizing the risk, stress for better monitoring of patients immune competency. msj.sagepub.com
The fourth paper presents the best practices for Ty use with a focus on patient selection and management. I was impressed with wide range of inputs thay got and the obvious cooperation from the super centers with hundreds of MS patients on Ty. They present their recommendations, factors, and recovery points in well laid out tables. Their changes include:
A. Longer washout period for prior immunosuppressants... longer than 6 months up to a year.
B. Strong recommendation for CD4+ screening. Potential use of CD4:CD8 ratio.
C. Stop Ty treatment after 6 months with positive antibodies.
D. Strong warning on interruption of Ty treatment after short exposure due to increased risk of hypersensitive reaction.
msj.sagepub.com
Time for the life scientists to weigh in,
graham
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