Cracked. com Americas Only Humor Site. Copyright 2. 00. Cracked is a Scripps company brand. Crackers Kamikaze KaitouWheelchair Kamikaze. Yes, folks, another post on Ocrevus. Hope Im not beating a dead horse here, but I feel this is a very important subject given the amount of hyperbolic press coverage this newly FDA approved drug has received. The Ocrevus picture is a complicated one, especially for patients with progressive MS. Its now the only approved drug for this form of the disease, which is a good thing. Unfortunately, there are still questions regarding the efficacy and risk associated with Ocrevus when used on the progressive MS population. Much of these questions can be accounted for by the drugs newness to the market because its riskreward profile in a real world setting has not yet been established. While this is true of all new drugs, the fact that the progressive MS population is clamoring for treatment options puts these uncertainties under a bright spotlight. I first read the below email exchange between two MS neurologists about a week ago on the invaluable MS Research Blog click here, which is written by the MS neurologists and researchers at the Barts and London School of Medicine in Great Britain. The neurologist who posted this exchange is Dr. Giovanni Giovanonni, who was one of the co authors of the Ocrevus progressive MS trial research paper. The other neuro involved in the exchange preferred to keep their anonymity. I posted a comment to Dr. Giovanni asking if I could repost this in Wheelchair Kamikaze to give it further exposure, and he agreed. A big thank you to him. Here then, is the dialogue on the use of Ocrevus in PPMS between Dr. Giovanonni and his anonymous colleague. Just to be clear, in all the verbiage between the linebreaks I refers to Dr. Giovanonni, and hisher refers to the other neurologist. Purple/v4/37/28/d6/3728d681-83a8-cd81-4600-08e0991a6b2f/icon350x350.png' alt='Crackers Kamikaze Lyrics' title='Crackers Kamikaze Lyrics' />NEJM is the New England Journal Of Medicine, in which the Ocrevus PPMS trial results were published. Ill add my two cents at the end of this post. I have started up another email exchange with a colleague about the ORATORIO ocrelizumab in PPMS study. I have asked himher if we could have this debate in the open on the blog, but heshe has asked to remain anonymous. When I respond to MS related questions that may be of interest to the broader community I prefer to answer them in the open, which is why I have redacted the discussion and posted it below The following are hisher primary questions You were a co author on the ocrelizumab in PPMS NEJM manuscript, which didnt really address the issue of ageinflammatory activity as markers for treatment response. Both the rituximab data in OLYMPUS and the Gadolinium data in the supplement of the NEJM article indicate that the population that benefits is the young patient with inflammatory activity. B cell depletion is not benign, especially in the older population, and the ocrelizumab manuscript infers that all PPMS patients should be treated with ocrelizumab. Are you really treating all of your PPMS patients with B cell depletion, and, if not, why didnt you push for more discussion about this issue in the NEJM paperMy response We tried to restrict the trial population as much as possible to mirror that of the responder subgroup in OLYMPUS rituximab in PPMS study. Please note the following specific inclusion criteria for the trial Age cut off of 5. Disease duration of symptoms of less than 1. EDSS score of more than 5. EDSS score of 5. 0 or less at screening. Documented history or the presence at screening of an elevated Ig. G index or at least one Ig. G oligoclonal band detected in the cerebrospinal fluidThe presence of absence of Gd enhancing lesions was not part of the inclusion criteria and hence should not be used to select patients for ocrelizumab treatment in the real life situation. Itext Pdf Template Create Template there. The detection of Gd enhancing lesions also depends on the frequency of imaging. If you are going to select patients for treatment I suggest you use the the three inclusion criteria above as your guide. I predict that these will probably exclude 7. PPMS clinic population. Please note that the trial population in the ORATORIO study was not typical of other PPMS trials the population was younger, less disabled, had higher proportion with Gd enhancing lesions at baseline and higher on study number of relapses. As I have said before there were strong trends in both the Gdve and Gd ve cohorts, therefore, we shouldnt limit treatment to patients with Gd enhancing lesions only. If we did this we would be denying many patients access to an effective treatment. I personally dont buy into MS being 2 or 3 diseases. MS is one disease and PPMS is simply more advanced MS if patients are active they should be offered treatment regardless of their presenting clinical phenotype. Regarding my own practice. We cant use rituximab in the UK the NHS wont pay for it and are unlikely to pay for ocrelizumab either. NICE will assess the cost effectiveness of ocrelizumab based on its price for relapsing forms of MS and in PPMS ocrelizumab will be compared to best supportive care. The latter means ocrelizumab is unlikely to pass the NICE cost effectiveness threshold. I am hoping that Roche, who will be marketing ocrelizumab in Europe, approach NICE and the NHS to discuss differential pricing and to offer ocrelizumab at a cheaper price for patients with PPMS. Differential pricing is a hot potatoe and I am not sure the NHS is ready for it but I live in hope for my patients. Please note ocrelizumab has yet to be licensed in Europe and we cant assume its license will be the same as the US. KAMIKAZE-T-SHIRT-ROCK-N-LOVE-NET-.jpg' alt='Crackers Kamikaze Definition' title='Crackers Kamikaze Definition' />Insiders Guide To The Cavalier King Charles Spaniel Doggy Names 2005 2011 www. Popular Pet Names Just like people, pets. With 325 varieties, can you believe theres any flavor we havent done Any flavor may be preordered with one dozen minimum, any size For mocktail varieties, look. Pehled. Skupina Slade byla jednou z vdch skupina glam rocku a v dob sv nejvt slvy to byla komern nejspnj skupina ve Spojenm. At present we offer our patients with active PPMS off label cladribine, a relatively cheap B cell depleting agent. Like all DMTs it is a choice and not all patients take up the offer. I am also aware that in the US a large number of neurologists are still using low dose methotrexate in PPMS. I am not sure we have enough data on B cell depletion in PPMS to make a call on whether it is benign or non benign. Hopefully, good quality safety data will emerge from post marketing surveillance studies. Philosophical Questions Philosophical Questions List 101 Philosophical questions to ask people, your friends or someone you know. What is the meaning of life Giochi Di Rubare Macchine I migliori ladri di auto sanno forzare una serratura e mettere in moto una macchina in pochi secondi. Ruba tutti i veicoli e semina la polizia. Crackers KamikazeeEn 1974, Slade fit le film rock Flame, unanimement acclam. Le critique de cinma Mark Kermode dit quil sagissait l du meilleur film sur le rock de tous les. The Amazing Kamikaze Syndrome is the eleventh studio album by the British rock group Slade. It was released on 3 December 1983 and reached No. UK charts. I suspect as with all immunosuppressive therapies it wont be benign. I would recommend telling all your patients about infusion reactions, the herpetic infection risk, the possible malignancy risk and the likelihood that in time they may develop hypogammaglobulinaemia and need Ig replacement therapy. Please note we have a large amount of clinical experience in children with agammaglobulineamia and these kids do well long term, as long as we keep the Ig levels normal. I am not sure you are correct in suggesting that we are recommending ocrelizumab for all comers. The trial population defines the group we are advocating its use in. I am surprised the FDA did not include the CSF findings in the label. If I was a regulator I would state that CSF ve PPMS should not be treated with ocrelizumab. Regarding discussion in the NEJM paper the editors of the NEJM essentially cull all speculative discussion and limit the discussion to issues in the trial. NEJM editors are renowned for rewriting submitted papers to keep them consistent for style. The NEJM article is not the forum for the kind of discussion you want to have. I suggest we have this discussion on the blog. Hisher response Thanks for your prompt and thoughtful response.