Clues to Why Humira Fails Some RA Patients | Arthritis Information

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TUESDAY, April 12 (HealthDay News) -- In a new study, close to a third of patients taking the arthritis drug Humira developed an immune system reaction to it that rendered it ineffective.

Researchers say the finding helps to explain why some people get relief from their rheumatoid arthritis symptoms while on Humira (adalimumab), which is made by Abbott Laboratories, while others gain little or no benefit. Humira belongs to a class of drugs known as biologics.

In those people for whom the drug is ineffective, the immune system realizes the drug is a foreign substance and develops antibodies to it, researchers explained. Those antibodies bind to the drug and prevent it from working.

"What the publication shows is that Humira, like many other biologic agents, may induce an immunological response against the drug," said senior study author Dr. Gerrit Jan Wolbink, a rheumatologist at Jan van Breemen Research Institute in the Netherlands. "The immunological response works against the drug. This is one of the explanations why some patients do not respond the way we hope they will."

Patients who were also taking methotrexate, another arthritis drug and an immunosuppressant, were less likely to develop the antibodies, according to the study in the April 13 issue of the Journal of the American Medical Association.

Researchers followed 272 patients taking Humira for about three years.

About 28 percent developed immune system antibodies against the drug. The reaction tended to happen within the first few months of starting treatment: About 67 percent of those who developed antibodies did so during the first 28 weeks.

Patients without antibodies had more of the drug circulating in their blood. Lower levels of the drug are a sign that the body's immune system is fighting the drug and it's being removed from the body, Jan Wolbink explained.

Whether or not patients developed antibodies was also linked to whether they got relief from their rheumatoid arthritis while on Humira.

Nearly half -- 48 percent -- of those without antibodies experienced a significant reduction of their arthritis symptoms while taking the drug, while only 13 percent of those who developed antidrug antibodies got similar relief.

And while 34 percent of patients without antibodies experienced remission, only 4 percent of those who developed antibodies did.

Patients who developed antibodies were also more likely to drop out of the study because of "treatment failure."

Humira is a tumor necrosis factor (TNF) inhibitor, which works by blocking the action of TNF, a substance known as a cytokine that contributes to the inflammation of rheumatoid arthritis and other conditions.

"If you make antibodies, then Humira doesn't block the action of TNF, and it doesn't work," Jan Wolbink said.

Dr. Olga Belostotsky, a rheumatologist and chief of allergy and immunology at Lennox Hill Hospital in New York City, said the research helps explain why some patients don't respond to Humira, and yet they do respond when switched to another drug in the same class of TNF inhibitors.

"It's because they don't have antibodies to the other drugs, even when it's another drug in the same group of medications," she said.

Belostotsky said the research suggests it's very important that patients start methotrexate to suppress the immune system before starting Humira.

What isn't known is why those 28 percent of patients developed antidrug antibodies while the rest didn't.

"Why antibodies develop in some people more than the others is unclear, and why people react more to some drugs than others is unclear," Belostotsky said

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This is what my RD has been telling me all along. Humira never worked for me from the get go, and most other biologics I have been on seem to work for a short time, then according to my RD, I develop  an immunological response, rendering it ineffective. Right now I am on Simponi 50 mg every two weeks instead of the recommended dose of once a month. I saw my RD on Monday, and was noted to have moderate to severe inflammation in all my joints, and my CRP was highly elevated. Not sure what we'll try next, he's reluctant to try Actemra because of the potential side effects. I just keep hoping that some new drug will come out that I won't develop antibodies to. Anyone else have this problem?                       Hi Gale, this happened to me with Enbrel after a year or so, I started having horrible allergic reactions.  I went through all kinds of test, elimination diet, changes in diet, (which turned out to be a really, really good change) and medications before we figured out I was having a reaction to the Enbrel.  Humira did nothing at all for me and I am now on Cimzia, which seems to be working well. (I take it like you do the Simponi - an injection every 2 weeks rather than 2 once a month.)  I realize there may be adverse side effects with Cimzia, as with any of the big gun RA drugs, but this is the very reason my RD keeps such a close eye on things.  I also know first hand the consequences of poorly treated RA - for me, it was RA lung disease and the rapid decline of my aortic valve (due to uncontrolled inflammation) leading to valve replacement.  For me, starting the drug has been a vast improvement in my lifestyle as it has helped considerably with my pain and mobility.

I hope you can find the perfect drug (or combination of drugs) for you to control your RA soon.  It sometimes seems all of our battles are uphill but, hopefully, you will soon be enjoying the ride from the slide down on the backside!  I do wish the powers that be could perfect, make available and affordable stem cell transplant as that seems to be the closest thing to a cure.    Big, big I USED TO GET THAT WITH CARROT JUICE AND FRESH APPLE JUICE BUT SINCE I SWITCHED FOODS AND ONLY EAT WHOPPERS AND FRIES IT NEVER HAPPENS. I've failed all of them due to this process but the odd thing is I did better on Humira and for a longer time (2years) than any of the others.  
 
Waddie, I'm really happy that you're doing well on Cimzia.  It's the only one I haven't tried and my RD wouldn't recommend it due to potential side effects  so I went on to Orencia and became very ill and am now going to start Rituxan that has more serious side effects than the others. 
 
I need to find out why to why she wouldn't recommend Cimzia and what side effects did she think would be problamatic. 
 
Brisen, hope that you and your RD can develop a treatment plan for you soon.  The decision making process is excruciatingly difficult.  Take care.  Lindy
LinB2011-04-14 14:43:09Lindy, I would be most interested in hearing what she has to say.  Please pm me if you want.  I've read all the pamphlets on all the drugs I've used and to me, they all have very similar warnings as to possible side effects.  The effect of Cimzia on me as far as RA is concerned was felt before I finished the loading doses and was to the good.  I was ready to move on to Rituxan as well and, if warranted,  will move to it in the future.  I do worry about side effects of all these drugs, but have experience worse from RA and will do what is needed to control my inflammation.  I drug my feet about starting Enbrel and suffered from RA lung and I won't make that same mistake again after that experience coupled with heart disease.  As most of you know, I went for some time after my diagnosis of RA using alternative medicine because I had no insurance.  It did not work for me so by the time I did have insurance, I was in rough shape with visible joint damage.

Also, for the record, FYI to anyone who cares, I have been though fasting, and still fast occasionally, elimination diet, eat no sweets as a rule, (other than an occasional lap of honey, dark chocolate or agave  Great Post!
See it really is not our imaginations that the drugs just stop working! Humira is my 3rd TNF. Two plus years on it and it is still working. Waddie, I did my research also and didn't see much difference in any of the meds as far as side effects.  Could be she had a patient that had a serious side effect from Cimzia and is skittish about using it.  Who knows. 
 
Serious side effects can occur and do occur. 
 
I just got through being hospitalized and pretty ill and had so much to talk to her about I didn't think to question her about her opposition to Cimzia.  I will when I see her in a couple of weeks. 
 
I too went the natural, alternative route and ended up with interstial lung disease from RA and other side effects because I knew that there were alternatives to the drugs......wrong!!  Like you I eat a well rounded diet, no sugar, boxed or preprepared foods.  Even if it doesn't have a direct impact on RA it keeps me fit in other ways so I can be stronger to fight the disease.  Take care.  Lindy
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