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home:othertreatments:antitnf [08.26.2017] – [Increased risk of infection] sallieqhome:othertreatments:antitnf [09.14.2022] (current) – external edit 127.0.0.1
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-Tumor necrosis factor-alpha or TNF-alpha is a cytokine critical for effective immune surveillance and is required for proper proliferation and function of natural killer cells, T cells, B cells, macrophages, and dendritic cells.(({{pubmed>long:16331857}})) Anti-TNF drugs, also known as TNF blockers, are drugs which interfere with the body's production of TNF-alpha.(({{pubmed>long: 18387510}}))+Tumor necrosis factor-alpha or TNF-alpha is a cytokine critical for effective immune surveillance and is required for proper proliferation and function of natural killer cells, T cells, B cells, macrophages, and dendritic cells.(({{pmid>long:16331857}})) Anti-TNF drugs, also known as TNF blockers, are drugs which interfere with the body's production of TNF-alpha.(({{pmid>long: 18387510}}))
  
 Anti-TNF drugs are expensive, ineffective at treating chronic disease and have a number of adverse effects. Also, anti-TNF inhibitors can make a patient feel temporarily less symptomatic, because they reduce immunopathology, the bacterial die-off reaction. Anti-TNF drugs are expensive, ineffective at treating chronic disease and have a number of adverse effects. Also, anti-TNF inhibitors can make a patient feel temporarily less symptomatic, because they reduce immunopathology, the bacterial die-off reaction.
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 During immunopathology, cytokines, are elevated. Although cytokines are usually associated with an inflammatory process, it has been demonstrated that TNF, interleukin-6 (IL-6) and IL-8 are involved in the immunopathological reaction, each peaking at different times throughout the response: TNF elevates first, shortly after antibiotic administration, followed by IL-6 at the onset of symptoms and finally IL-8. During immunopathology, cytokines, are elevated. Although cytokines are usually associated with an inflammatory process, it has been demonstrated that TNF, interleukin-6 (IL-6) and IL-8 are involved in the immunopathological reaction, each peaking at different times throughout the response: TNF elevates first, shortly after antibiotic administration, followed by IL-6 at the onset of symptoms and finally IL-8.
  
-The release of cytokines appears to be essential for recovery after an infection. One study found that the cytokine TNF-alpha is necessary for the proper expression of acquired specific resistance following infection with //Mycobacterium tuberculosis//.(({{pubmed>long:18544042}})) (({{pubmed>long:12852719}})) (({{pubmed>long:15216471}})) Another effect of the use of TNF blockers is to break or reduce the formation of granuloma, one of the body's mechanisms to control bacterial pathogens.(({{pubmed>long:16322600}}))+The release of cytokines appears to be essential for recovery after an infection. One study found that the cytokine TNF-alpha is necessary for the proper expression of acquired specific resistance following infection with //Mycobacterium tuberculosis//.(({{pmid>long:18544042}})) (({{pmid>long:12852719}})) (({{pmid>long:15216471}})) Another effect of the use of TNF blockers is to break or reduce the formation of granuloma, one of the body's mechanisms to control bacterial pathogens.(({{pmid>long:16322600}}))
  
 For these reasons among others, TNF-alpha inhibitors, drugs which suppress the cytokine, are contraindicated for MP patients. For these reasons among others, TNF-alpha inhibitors, drugs which suppress the cytokine, are contraindicated for MP patients.
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 ===== Increased risk of infection ===== ===== Increased risk of infection =====
  
-One recent systematic review of the adverse effects of anti-TNF therapies as they were used in rheumatoid arthritis concluded that patients taking the drugs are at 2.0 times higher risk for serious infections.(({{pubmed>long:16705109}})) The study's authors concluded that these side effects were dose-dependent.+One recent systematic review of the adverse effects of anti-TNF therapies as they were used in rheumatoid arthritis concluded that patients taking the drugs are at 2.0 times higher risk for serious infections.(({{pmid>long:16705109}})) The study's authors concluded that these side effects were dose-dependent.
  
  
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 //**U.S. Food and Drug Administration**//, [[https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/inflcen111099lb.pdf|page 6 : Warnings]]</blockquote> //**U.S. Food and Drug Administration**//, [[https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/inflcen111099lb.pdf|page 6 : Warnings]]</blockquote>
  
-//M. tuberculosis// is one such infection.(({{pubmed>long:19565495}}))+//M. tuberculosis// is one such infection.(({{pmid>long:19565495}}))
  
 <blockquote>Cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumour necrosis factor (TNF) alpha. TNF-alpha has a central role in mycobacterial infection and disease. Accordingly, progression of recently acquired tuberculosis infection or reactivation of remotely acquired infection //should be expected// with the use of anti-TNF agents. <blockquote>Cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumour necrosis factor (TNF) alpha. TNF-alpha has a central role in mycobacterial infection and disease. Accordingly, progression of recently acquired tuberculosis infection or reactivation of remotely acquired infection //should be expected// with the use of anti-TNF agents.
  
-//**Michael A. Gardam,** et al.// (({{pubmed>long:12614731}}))</blockquote> +//**Michael A. Gardam,** et al.// (({{pmid>long:12614731}}))</blockquote> 
  
-To reduce the likelihood of contracting or exacerbating tuberculosis, prospective patients are routinely tested for infection via a skin test. However, as some researchers have noted, TB skin tests on patients treated with immunosupressants, which are routinely used on rheumatoid arthritis patients, are not reliable, because they result in false negatives.(({{pubmed>long:12614731}}))+To reduce the likelihood of contracting or exacerbating tuberculosis, prospective patients are routinely tested for infection via a skin test. However, as some researchers have noted, TB skin tests on patients treated with immunosupressants, which are routinely used on rheumatoid arthritis patients, are not reliable, because they result in false negatives.(({{pmid>long:12614731}}))
  
-"Exaggerated //Borreliosis// infections" have been noted(({{pubmed>long:20184613}})) as have been fatal fungal infections. In 2008, the FDA ordered stronger warnings on Enbrel, Remicade, Humira and Cimzia due to increased risk of fungal infections.+"Exaggerated //Borreliosis// infections" have been noted(({{pmid>long:20184613}})) as have been fatal fungal infections. In 2008, the FDA ordered stronger warnings on Enbrel, Remicade, Humira and Cimzia due to increased risk of fungal infections.
  
 Researchers have also observed reactivation of latent viral infections, namely hepatitis B in patients who are chronic carriers of the virus. Researchers have also observed reactivation of latent viral infections, namely hepatitis B in patients who are chronic carriers of the virus.
  
-For these reasons, physicians are [[http://www.fda.gov/medwatch/SAFETY/2004/Remicade_12-22-04_PI.pdf|strongly advised]] by the FDA not to prescribe TNF blockers to patients who suffer from active or latent infections and to discontinue therapy in the event of serious infection. Yet, this advisory is strikingly incomplete. In fact, all patients who suffer from diseases for which an anti-TNF agent could possibly indicated suffer from a chronic bacterial infection, a fact which underscores the importance of not taking such drugs.+For these reasons, physicians are [[https://www.fda.gov/medwatch/SAFETY/2004/Remicade_12-22-04_PI.pdf|strongly advised]] by the FDA not to prescribe TNF blockers to patients who suffer from active or latent infections and to discontinue therapy in the event of serious infection. Yet, this advisory is strikingly incomplete. In fact, all patients who suffer from diseases for which an anti-TNF agent could possibly indicated suffer from a chronic bacterial infection, a fact which underscores the importance of not taking such drugs.
  
 ===== Other adverse effects ====== ===== Other adverse effects ======
  
-  * **Allergic reaction** – Some patients report an allergic response to Remicade. One possible reason may be that the [[http://cancerweb.ncl.ac.uk/cgi-bin/omd?chimeric+molecule|chimeric monoclonal]] antibody in Remicade is part human, part mouse. Exposed to purely mouse (murine) antibodies, human immune systems naturally develop human antibodies to the foreign mouse proteins, a process which can trigger an allergic-like response. +  * **Allergic reaction** – Some patients report an allergic response to Remicade. One possible reason may be that the [[https://cancerweb.ncl.ac.uk/cgi-bin/omd?chimeric+molecule|chimeric monoclonal]] antibody in Remicade is part human, part mouse. Exposed to purely mouse (murine) antibodies, human immune systems naturally develop human antibodies to the foreign mouse proteins, a process which can trigger an allergic-like response. 
   * **Congestive heart failure** – Exacerbation of CHF is a major side effect of Remicade use in patients with moderate to severe CHF. This is especially problematic in that many sarcoidosis patients do not know that they have cardiac involvement.    * **Congestive heart failure** – Exacerbation of CHF is a major side effect of Remicade use in patients with moderate to severe CHF. This is especially problematic in that many sarcoidosis patients do not know that they have cardiac involvement. 
-  * **Liver problems** – [[http://www.fda.gov/medwatch/SAFETY/2004/Remicade_12-22-04_PI.pdf|According to the FDA]], patients taking Remicade can (but rarely) experience severe hepatic reactions including acute liver failure, jaundice, hepatitis and cholestasis. +  * **Liver problems** – [[https://www.fda.gov/medwatch/SAFETY/2004/Remicade_12-22-04_PI.pdf|According to the FDA]], patients taking Remicade can (but rarely) experience severe hepatic reactions including acute liver failure, jaundice, hepatitis and cholestasis. 
-  * **Skin problems** – In one prospective trial, 25% of patients on TNF-alpha-blocking therapy suffered from a dermatological condition that led them to visit a skin specialist. In a control group of patients who were not undergoing TNF-alpha blocking therapy and had less severe disease only 13% visited a dermatologist during the same period of time.(({{pubmed>long:15899052}})) +  * **Skin problems** – In one prospective trial, 25% of patients on TNF-alpha-blocking therapy suffered from a dermatological condition that led them to visit a skin specialist. In a control group of patients who were not undergoing TNF-alpha blocking therapy and had less severe disease only 13% visited a dermatologist during the same period of time.(({{pmid>long:15899052}})) 
-  * **Cancer** – One recent systematic review of the adverse effects of anti-TNF therapies as they were used in rheumatoid arthritis concluded that patients taking the drugs are at 3.3 times higher risk for "malignancies."(({{pubmed>long:16705109}})) The study's authors concluded that these side effects were dose-dependent. Since then, the FDA has issued [[http://www.fda.gov/CDER/drug/early_comm/TNF_blockers.htm|an early communication]]  about an ongoing investigation of approximately 30 reports of cancer in children and young adults. More recently, a study of over 20,000 US military veterans show that nonmelanoma skin cancer risk is about one third higher for patients with rheumatoid arthritis treated with TNF inhibitors than for similar patients treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs).(({{pubmed>long:21415022}}))+  * **Cancer** – One recent systematic review of the adverse effects of anti-TNF therapies as they were used in rheumatoid arthritis concluded that patients taking the drugs are at 3.3 times higher risk for "malignancies."(({{pmid>long:16705109}})) The study's authors concluded that these side effects were dose-dependent. Since then, the FDA has issued [[https://www.fda.gov/CDER/drug/early_comm/TNF_blockers.htm|an early communication]]  about an ongoing investigation of approximately 30 reports of cancer in children and young adults. More recently, a study of over 20,000 US military veterans show that nonmelanoma skin cancer risk is about one third higher for patients with rheumatoid arthritis treated with TNF inhibitors than for similar patients treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs).(({{pmid>long:21415022}}))
  
  
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 Considering that Abbott’s Humira was the company’s best-selling product in 2007 with over $3 billion in sales, and Remicade also topped Schering-Plough’s portfolio with sales of $1.65 billion, there is minimal hope that such companies will be willing to embrace a true understanding of how their drugs foster the development of chronic disease. Considering that Abbott’s Humira was the company’s best-selling product in 2007 with over $3 billion in sales, and Remicade also topped Schering-Plough’s portfolio with sales of $1.65 billion, there is minimal hope that such companies will be willing to embrace a true understanding of how their drugs foster the development of chronic disease.
  
-Insurance coverage and baseline cost of anti-TNF drugs varies, but patients in the United States and Canada [[http://www.healingwell.com/community/default.aspx?f=38&m=1043934|have reported]] being charged $4,600 or more for a single treatment of Remicade. According to one estimate, $1,000 of the $4,600 goes to pay the prescribing physician's clinical group.+Insurance coverage and baseline cost of anti-TNF drugs varies, but patients in the United States and Canada [[https://www.healingwell.com/community/default.aspx?f=38&m=1043934|have reported]] being charged $4,600 or more for a single treatment of Remicade. According to one estimate, $1,000 of the $4,600 goes to pay the prescribing physician's clinical group.
  
-One citizen watchdog group, the New Jersey Citizen Action (NJCA), [[http://www.prescriptionaccess.org/docs/remicade.pdf|filed a lawsuit]] to stop Remicade from being promoted by promising doctors windfall profits when they prescribe the drug. +One citizen watchdog group, the New Jersey Citizen Action (NJCA), [[https://www.prescriptionaccess.org/docs/remicade.pdf|filed a lawsuit]] to stop Remicade from being promoted by promising doctors windfall profits when they prescribe the drug. 
  
  
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 {{tag> }} {{tag> }}
  
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
  
  
   * Legacy content   * Legacy content
-    * http://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=28080#p28080 s32 +    * https://www.marshallprotocol.com/view_topic.php?id=3094&forum_id=37&jump_to=28080#p28080 s32 
-===== References =====+===== References =====</nodisp> 
home/othertreatments/antitnf.txt · Last modified: 09.14.2022 by 127.0.0.1
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