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#238061 - 09/17/06 11:20 PM How ANTI-TNF Works
Moonbees Offline


Registered: 06/17/03
Posts: 2884
Loc: Alabama USA
Originally posted in the main forum by Wolverine (Thanks,Brad) and placed here as a permanent post.

What is anti-TNF ?:

TNF (Tumour Necrosis Factor) is one of a number of chemicals called cytokines which help the body defend itself from outside attack (ie virus, bacteria etc) by causing inflammation. Normally inflammation is important because it baths the area in fluid to cushion damaged tissue, increases blood flow to allow the immune system to kill invaders and causes pain to ensure no further damage is done. However, sometimes the body fails to recognized when the danger period of outside attack has ended and then chronic inflammation occurs. The body keeps producing inflammatory chemicals like TNF even when they are not needed any more. A drug which blocks these inflammatory chemicals can stop the inflammation cycle. Anti-TNF is a drug which is used to stop inflammation by blocking the TNF that is made by the body.

How is anti-TNF different than other anti-inflammatories like aspirin or ibuprofen ?

Anti-TNF is a disease modifying drug. This means it acts on the specific chemicals involved in AS change. Drugs like aspirin and ibuprofen act on the symptoms of AS but do not change the actual disease itself. Treatments like sulfasalazine may be effective in people with arthritis in the hands and feet (ie non-spinal disease) but have only small effects on severe AS and arthritis mainly in the spine. However, high level of TNF are found in the sacroiliac joints of patients with ankylosing spondylitis. If the TNF itself could be removed, then we could prevent damage to these joints and so actually alter the disease progression. Potentially anti-TNF should reduce the fatigue, pain, swelling, improve mobility and prevent further damage. High TNF levels are also found in people with psoriatic arthritis, rheumatoid arthritis and crohn's disease, and these conditions also improve with anti-TNF.



Is there evidence that anti-TNF does stop the inflammation involved in ankylosing spondylitis ?

There have been dramatic and impressive results in the 300 people with AS who have been involved the trials carried out (in Germany, Belgium, Canada, Spain, England, France and America). For example 18 patients in Canada showed excellent improvement in function, disease activity, fatigue, pain and radiological imaging (MRI). In the short term (over 14 weeks) it was a very effective treatment. In all trials to date there has been a dramatic reduction in symptoms of AS and in the progression of joint destruction. In ankylosing spondylitis both spinal symptoms and peripheral (i.e. hands, feet, knees etc) involvement show fast and significant improvement. Anti-TNF also works to give great improvement in the disorders associated with spondylitis such as psoriasis and crohns disease (though not ulcerative colitis). It has been used for up to 5 years in patients with Rheumatoid Arthritis and in these patients the improvement in symptoms was sustained and the anti-TNF was shown to protect the joints from further structural damage. Current work suggests that anti-TNF seems even more effective in AS than in rheumatoid arthritis.

In the trials carried out to date the reduction in disease activity has been between 50%-93%. Positive effects can occur as early as one day after treatment and last for 12 weeks. The best responses have been obtained in people with early disease. However, even in people with almost complete fusion there was still 45% improvement in disease activity at after 30 weeks (ie 7 months) of treatment.

In a small trial on 29 people, anti-TNF seems to have help reduce osteoporosis. After 6 months the people taking part in the trial showed a higher bone mineral density.

Does everyone who takes it get this dramatic reduction in disease ?

No. The effect does vary with different individuals. There are some non-responders in all trials (i.e. no change in disease). However, about 80% of people do show an improvement. This is still very impressive for a new drug.

Are there any problems with anti-TNF ?

Yes. There is some need for caution. :

Complete remission of disease has rarely been seen. So some inflammation does appear to remain and this means that other chemicals are also involved in the inflammatory process and these are not affected by anti-TNF.

When the anti-TNF therapy is stopped the ankylosing spondylitis comes back. Therefore a person needs to continue taking the anti-TNF, perhaps for life.

There is the possibility that the body could become immune/accustomed to the anti-TNF and after a time it may not work. Therefore, it is possible that anti-TNF may not work for life.

As with any drug which affects the immune system (i.e. reduces inflammation) there is the risk of infection as the bodyísí ability to defend itself is reduced. Upper respiratory infections are more common among people taking anti-TNF and there have been cases of tuberculosis reported. [1-5 in 10,000 people taking the drug]. Other infections reported include : pneumonia and meningitis. The increased risk of pneumonia is 0.5% or 1 in 200. Therefore, if a person carries the TB bacteria this may become active when taking anti-TNF.

Some rheumatologists feel that because the immune system is suppressed , there may be a theoretical risk of developing some types of cancer. However, there has been no increased occurrence of cancer in people taking anti-TNF to date.

Some people [1 in 1000] develop lupus like disease (this is another autoimmune arthritis) which goes away when the anti-TNF treatment is stopped.

People with congestive heart failure can not take anti-TNF.

The reasons that people have stopped taking part in trials also include : septic osteomyelitis (ie infection of the bone) and hypersensitivity (ie a skin reaction where the drug is injected). 20% of people taking infliximab (one type of anti-TNF) showed a local skin reaction and 3% (or 3 in 100) stopped the drug due to the skin reaction.

Many of these side effects are rare and some of the risks are theoretical. However, because of these risks anti-TNF is currently only considered for people with severe and active ankylosing spondylitis.

Can I get anti-TNF from my doctor ?

Anti-TNF became available in Europe in May 2003. However, it is very expensive and it is not as easy to take as pill. There are 2 types of anti-TNF.

Infliximab which needs to be given as an intravenous infusion. This means attending a hospital and having the drug by drip, slowing releasing it into the blood stream over the period of 2 hours. This needs to be done every 6-8 weeks.

Etanercept which is self injected much the same as people who are diabetic inject themselves. People give themselves an injection twice a week.

Thus in summary, anti-TNF is very new and exciting and the first disease modifying drug to have a significant effect in ankylosing spondylitis. Potentially anti-TNF could help a great number of people in the future. However, it is too early to be sure of the long term benefits and side effects of this therapy.

References :

Braun J et al. Thera py of ankylosing spondylitis and other spondyloarthritides : established medical treatment , anti-TNF alpha therapy and other novel approaches. Arthritis Res. 2002; 4(5): 307-21.

Maksymowych WP. et al. Infliximab in ankylosing spondylitis : a prospective observational inception cohort analysis of efficacy and safety. J Rheuamtol 2002; 29(5): 959-65.

Braun J. et al. Anti-tumour necrosis factor alpha therapy for ankyloising spondylitis : international experience. Ann Rheum Dis. 2002; 61 Suppl 3: III51-III60.

Braun J et al. Treatment of active ankylosing spondylitis with infiximab : a randomised controlled multicentre trial. Lancet 2002; 359 (9313): 1187-93.

Gorman J et al. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002; 346(18): 1349-56.

Sieper J et al. New treatment options in ankylosing spondylitis : a role for anti-TNF alpha therapy. Ann Rheum Dis 2001; 60 Suppl 3: iii58-61.

Marzo-Ortega H et al. Efficacy of etanercept in the treatment of the entheseal pathology in resistant spondylarthritipathy : a clinical and magnetic resonance imaging study. Arthritis Rheum 2001; 44(9): 2112-7.

Braun J, Sieper J, Breban M, Collantes-Estevez, Davis J, Inman R, Marzo-Ortega H, Mielants H. Anti-tumor necrosis factor alpha therapy for ankyloisng spondylitis: international experineces. Ann Rheum Dis 2002; 61: S111.

Dernis E, Roux C, Breban M, Dougados M. Infliximab in spondylarthropathy- Influence on bone mineral density. Clin Exp Rheumatol 2002; 20 (Suppl. 28): S185-S186.

Antoni C, Braun J. Side effects of anti-TNF therapy : Current knowledge. Clin Exp Rheumatol 2002; 20 (Suppl. 28): S152-S157.
_________________________
[color:"#006666"]Life itself is the most wonderful fairy tale.

~~Hans Christian Andersen


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#238062 - 09/19/08 01:12 PM Re: How ANTI-TNF Works [Re: Moonbees]
tiredofpain Offline
Silver_AS_Kicker

Registered: 06/14/08
Posts: 1482
Loc: Canada
Thank you again!

In addition to the Etanercept or Enbrel, there is Humira and I'm told that recent studies (sorry, no refs available) indicate that Humira may also be beneficial for Ulcerative Colitis...I'm not seeing that personally but it's something my GI specialist told me.

My guess is that the studies mentioned pumped their numbers a bit. Judging from my own experience and those of others in here, a 50+% improvement is pretty dang good. I'd put my own at about 35%-40% - when compared to what 0% feels like, I would classify both Enbrel and Humira as "wonder-drugs".

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#238063 - 12/04/08 03:46 PM Re: How ANTI-TNF Works [Re: tiredofpain]
tiredofpain Offline
Silver_AS_Kicker

Registered: 06/14/08
Posts: 1482
Loc: Canada
Just a quick note to update my post above:

My enthusiasm has diminished significantly since I wrote that! I'm thinking weekly Humira shots are maybe, on a good day, half as effective as I initially thought. They are better than anything else I've seen yet and I hear a lot of people singing their praises...I've tried them both and am merely, mildly encouraged by them.

Can't really say whether my impressions of my pain have altered (variable subjectivity?) or if the effectiveness of the drugs have tapered off over time...who knows?

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#238064 - 07/15/09 06:34 AM Re: How ANTI-TNF Works [Re: Moonbees]
kesav Offline
Member

Registered: 07/13/09
Posts: 38
Loc: sydney,australia
Thanks a lot for such valuable information.
_________________________
Take Care Kesav

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#448949 - 08/07/11 10:40 PM Re: How ANTI-TNF Works [Re: kesav]
Johnjob Offline
New_Member

Registered: 07/14/11
Posts: 3
Loc: Beijing, China
Thank you very much.
_________________________
To see a World in a Grain of Sand
And a Heaven in a Wild Flower
Hold Infinity in the palm of your hand
And Eternity in an hour

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#467035 - 04/11/12 02:12 AM Re: How ANTI-TNF Works [Re: tiredofpain]
Merci Offline
Lurker

Registered: 03/18/11
Posts: 1
This is the first time I have been on this website. So please bear with me.. I am not a computer guru at all. Actually this will be a little test for me. I was on Cimzia injections for 6 months, now on Humira injections for 6 months. No change, still in severe pain everywhere. I have had over 50 cortisone injections under x-ray in the last 4 months. Can't take oral prednisone, it raises my B/P and gives me panic attacks. In the last 1.5 yrs, my Medical Insurance has paid out $34,000 in meds for me, almost all of which are in ziploc bags tucked away. None of them work. Going for PT now to get my feet able to move. 40mg of percoset a day and not a bit of relief along with other meds. I am doomed... and about ready to throw in the towel..

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#467051 - 04/11/12 11:43 AM Re: How ANTI-TNF Works [Re: Merci]
gbash Offline
Master_AS_Kicker

Registered: 10/09/08
Posts: 890
Loc: Oklahoma
Merci,

Many of us on this site had bad problems with the DMARDs and biologics. For me, Enbrel gave me MS, and sulfasalazine wreaked havoc with my digestive system. Without other options, I tried the no-starch diet (NSD) and was amazed at how well it worked to reduce my pain to tolerable levels. Please take the time to read more about it on this site, and good luck.

--Greg
_________________________
AS symptoms started 1991. Official dx in 2006 with HLA-B27+, fused SIJ, bone spurs in back, extreme rib/hip pain, and other family with SpA. Started Enbrel in 2006 with good results, but stopped in 2010 due to nerve damage (MS) from it. Now getting good results with no-starch diet.

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#478552 - 10/17/12 04:43 PM Re: How ANTI-TNF Works [Re: Moonbees]
Bry4 Offline
New_Member

Registered: 10/08/12
Posts: 3
i started Syphoni because insurance wouln not cover Humera...now i just feel like i have no energy what so ever..anyone eles having this happen? been two weeks since my first injection. just need to know im not loosing my mind because thats kinda how i feel right now...thanks for listening

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#478570 - 10/17/12 08:38 PM Re: How ANTI-TNF Works [Re: Bry4]
millford Offline
Member

Registered: 01/18/11
Posts: 35
Loc: Copenhagen, Denmark
Hey Bry

Sorry to hear you're not well. First I'll say that 2 weeks is in no way enough time to gauge the effect of a TNF blocker. In some cases it can take up to 3 months before any positive effect is felt at all, and up to a year for the full effect of the drug. Fatigue can be a side-effect. Especially in the beginning when you're body is "adjusting" to the new drug.

I felt the same way as you in when I started, but I'm sure that was also mental exhaustion. All the anxiety knowing I was going to start this "dangerous" drug with all those horrible side-effects, that I would most certainly get. All of them. I didn't. Some do, of course, but they are few. You might have to live with some some side-effects, but usually they are acceptable.

My advice to try and relax a little. Fatigue is one of the most common side-effect, but also in it self, not something to worry about. You should make a list with all your worries and questions, and call/see your rheumatologist if you have one. If you don't, or can't wait for some answers, call the Simponi helpline in your country. If there is one. Search on Google.

I hope everything goes well for you. Let us know how it goes smile

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#498238 - 12/10/13 12:02 AM Re: How ANTI-TNF Works [Re: Moonbees]
Ivtec Offline
New_Member

Registered: 06/30/13
Posts: 3
Loc: Jakarta
Hey Bry,
First of all im a newbie here, just starting to read the group,and i dont know if anyof you still on this group. Wow this is a last year msg.i am using simponi like you do, for 5 month already,ongoing.so far i felt fatique ..but still tolerable...maybe just like Millford said,my body is adapting to this new drug..im happy to be here. There is someone to share and understand this agony..and like many others i just realized this symtomps after 10 or more year..and if not controlled it is worsen everyday..so yeah even this tnf cost a fortune but still manage to give me a good quality life...cheers to that...

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