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Biotech / Medical : Immunex -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (543)	8/16/2001 12:03:11 AM
From: scaram(o)uche	Read Replies (1) \| Respond to of 656

>> Black Box Warning/RISK OF INFECTIONS << Mike Collins, at Bayer (Cutter Biological, Berkeley), demonstrated that passive admin. of anti-TNF led to an increased frequency of death in an experimental Listeria infection. This was using the Chiron antibody, in 1986. Mike had set up a number of in vivo assays for various bacterial pathogens. You handed him an antibody, and you got back data that was open and shut. His assays were reproducible to a ridiculous extent. Fifteen years later, we've got the expected black box. For those who might want to understand a bit about the mechanism...... inflammatory responses are generally good things. They protect you. Things can get out of hand (sepsis, rheumatoid arthritis, etc.), however. If you give a ton of bacterial lipopolysaccharide to an experimental animal or human, you'll kill it. If you give a little bit of lipopolysaccharide to an experimental animal and then challenge them later with the lethal dose, they can survive. This is called endotoxin (lipopolysaccharide) tolerance. Lipopolysaccharide induces a TNF response, and, no surprise, a little TNF can also protect against a lethal challenge with lipopolysaccharide. One of the mediators of endotoxin tolerance is TNF. Circular rationale...... if you take TNF (or cells that produce TNF) out of the system at the wrong time, you remove the protective response. Thus..... while anti-TNF is highly effective for certain chronic inflammatory diseases, it can also disable an important element of innate immunity.

To: Biomaven who wrote (543)	8/16/2001 12:05:26 AM
From: IRWIN JAMES FRANKEL	Respond to of 656

Looks like the AMGN drug also requires DAILY injection - ouch. ij

To: Biomaven who wrote (543)	8/16/2001 7:31:25 AM
From: dalroi	Respond to of 656

Peter, concerning increased infection rate if i remember correctly , remicade has to be given with an immunosupressive agent (MTX ??? names oh names memory can play tricks) to prevent induction of anti remicade ab couldnt that also be the reason why its predominantly remicade and not enbrel which has those problem cheers Stefaan Drug Mix Halts Joint Erosion In Persistent Arthritis NEJM 11/30/2000 By Anne MacLennan Repeated doses of infliximab(Remicade) combined with methotrexate reduces the symptoms of rheumatoid arthritis and also halt progression of joint damage in patients who do not respond to methotrexate therapy, a study has found. Neutralization of tumor necrosis factor alpha (TNF-alpha) for three to six months is known to reduce symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to achieve a more sustained benefit-and its effect on joint damage-has been unknown. Participants in this trial were 428 patients with active rheumatoid arthritis despite methotrexate therapy. For 54 weeks, they were treated with placebo or infliximab, a chimeric monoclonal antibody against TNF-alpha, in intravenous doses of three or 10 mg per kilogram of body weight every four or eight weeks in combination with oral methotrexate. Clinical responses were assessed according to American College of Rheumatology criteria, quality of life with a health-status questionnaire and effect on joint damage radiographically. The infliximab/methotrexate combination was well tolerated and produced a significantly greater reduction in symptoms and signs of rheumatoid arthritis than did methotrexate therapy alone. Quality of life was also significantly better with the combination than the methotrexate alone. Furthermore, while radiographic evidence of joint damage increased in those taking methotrexate alone, it did not in the combined-therapy groups. Whether or not they had a clinical response to therapy, infliximab-treated patients showed no radiographic evidence of progression of joint damage. A comment suggests it is now reasonable to argue that TNF-alpha inhibitors should be used as early as possible in all patients with documented rheumatoid arthritis. The comment refers to evidence in both this and a related study [See Etanercept Curbs Early Rheumatoid Arthritis-vis A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis]. N Engl J Med 2000;343:1594-602