Antibodies Lessen Effectiveness of Adalimumab / Humira
A new study proves what many suspected – that Rheumatoid Arthritis patients develop antibodies against adalimumab (Humira) which lessen the effectiveness of the drug. Previous studies have shown this to be true for other Biologic treatments as well.
Anti-adalimumab antibodies: another front in our battle against RA
Doctors in the Netherlands found 28% of patients developed antibodies to Humira (adalimumab), most of them (67%) within the first few months of treatment. They measured serum adalimumab concentrations and “antiadalimumab” antibodies and found that patients who developed the antibodies had lower serum concentration of adalimumab (that means less Humira) in their bodies. They concluded that “the development of antidrug antibodies was associated with lower adalimumab concentration and lower likelihood of minimal disease activity or clinical remission.”
The report, Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up, followed 272 patients for three years. One of the most dramatic factors was the lowered likelihood of achieving minimal disease activity (or clinical remission) in patients who developed the antibodies against Humira:
“Ninety-five of 196 patients (48%) without antiadalimumab antibodies had minimal disease activity vs 10 of 76 patients (13%) with antiadalimumab antibodies; patients with antiadalimumab antibodies less often had sustained minimal disease activity score in 28 joints (DAS28) (< 3.2; HR, 3.6; 95% CI, 1.8-7.2; P < .001) compared with antiadalimumab antibody–negative ones. Three of 76 patients (4%) with antiadalimumab antibodies achieved sustained remission compared with 67 of 196 (34%) antiadalimumab antibody–negative ones; patients with antiadalimumab antibodies less often achieved remission (DAS28 < 2.6; HR, 7.1; 95% CI, 2.1-23.4; P < .001) compared with antiadalimumab antibody–negative ones.”
What patients know about adalimumab treatment failure
1) Many don’t respond to Biologics anyway.
For many patients, blocking TNF-alpha doesn’t improve RA symptoms. As I read a lot of press reports of this study, this fact was not mentioned. I’m just tired of reading and hearing everywhere the assumption that Biologics work on all patients until they eventually stop working. The treatments we have today don’t work at all in at least 1/3 of patients. And most people who do “respond” still live with symptoms of RA since a good response is often no more than twenty to fifty percent improvement.
2) Methotrexate can help avoid antibodies.
Only 4% of patients with antibodies to Humira “achieved remission,” compared with 34% of those without antibodies. So part of the game of RA treatment is to avoid creating antibodies that can neuter the treatment. Patients who also took methotrexate were less likely to develop the antibodies since methotrexate suppresses the immune system.
Of course patients hope new treatments can be created that can out-smart our immune systems completely, preventing antibodies from developing. Evidently, that’s more difficult than many of us can visualize.
Recommended reading
- Which Biologic Treatment Should RA Patients Try Next?
- How Soon Should You Switch Biologics for Rheumatoid Arthritis?
- Cost effectiveness: News about Rheumatoid Arthritis Treatment Options
- Side by side: Comparison of Biologics for Rheumatoid Arthritis (RA)
- How well do Biologic medications help Rheumatoid Arthritis?
Thank you for posting this study, Kelly. It’s great to see the research behing the reality that many of us have faced. I have been taking Enbrel for about 8 months. Over the past 2 months, I have noticed a dramatic increase in pain and stiffness. I am fairly certain that the Enbrel is losing effectiveness, but I do not want to switch biologics since Enbrel worked so well for so many months. I should add that I am not taking Mtx (side effects were not tolerable). I’ve just added Arava, and I hope that it will allow me to continue to do well on Enbrel for a long time to come. Do we know if Arava acts similar to Mtx in terms of antibody prevention?
I do know Arava is used sometimes as a substitute, but mtx is considered the safest & most effective so most docs choose it first. I haven’t seen any study that does a side by side comparison. Isn’t it fun to have a disease they are still learning how to treat? Ha. 🙂
Marie, I used Enbrel for 8 months. At first I noticed a good improvement, by 8 months it was all gone. Like maybe I built up antibodies to it?? Now on Humira, it’s effectiveness seems to depend on my activity and stress level. I better just sit and be good or RA is gonna get me. The big telltale sign that Enbrel stopped working was an increase in my fever. It came on slowly, so I didn’t notice, but one day my husband did and I started watching it and I had a fever every day. I have been on Humira for 8 months now and my fever has finally slowed down for the last 2 weeks, at least temporarily as my activity and stress level has reduced also. We shall see what happens next. No miracles so far.
It’s baaack! It was a nice little reprieve, but short.
I have come to the conclusion that 50% improvement is probably the best I’ll do. I no longer am excited about trying a new possible (biologic) cure! I have also noted that my RA is indeed progressing ever so slowly, bit by bit a little more of my resiliency is taken away. This is probably considered a bad attitude, but I’m just gonna be glad for what I have now and not get my hopes up for more – only to be disappointed. I am living for today, hoping for tomorrow, but sorry, not expecting miracles.
So what is the general consensus? That Humira is not worth taking? I’d like feedback on this.
I was supposed to start injections within the next three months or so. Now I’m wondering what to do. The main issue is that Medicare will only cover certain RA drugs in my state, and Humira is one of the only ones.
I didn’t get that impression, Jackie. There’s no way to know whether you’ll be one of the lucky ones who respond really well. Those people must sure think its worth it to get a reduction in symptoms. And there is the hope of slowing damage too of course.
Jackie, they are all worth a try, even if we only get a few months or 2 years of relief! Everyone is so different and you never know how your experience will be. I think overall I’ve had better results with Humira than Enbrel. My RA keeps changing though and progressing. Always keep hope, and trust in God, there is no better med than this.
In 2005 I was on Humira and it didn’t work at all for me. Today I still take Metho/Prednisone/folic acid with good results. This has been the only treatment that has worked for me. I’m not pain-free but it is difficult to judge how much of my pain is from all the prior damage from RA vs. pain from flares. I’ll deal with the pain as long as joint damage is controlled which it seems to be.
Hi Kelly,
Immunogenicity is a problem with some large molecule treatments (proteins and antibodies) and it isn’t special to RA. It can happen with just about any large molecule therapy. Fortunately, the biotech world has developed technologies that can help minimize this by creating humanized or fully human molecules. But if the body still recognizes it a foreign then it will create antibodies to it regardless of how “human” it is.
I know there are some that look at our available biologic treatments for RA and note that we have 5 anti-TNF agents. While we have 5 they’re all different. One is a chimeric mAb. Two are human mAbs. One is a humanized mAb that has its heavy chain removed and is PEGylated so it lasts longer in the body. One is a trap for TNFa put on human IGg. I guess where I’m going with this is that although we have 5, they don’t always work with particular patients or they stop working. When and if that happens we have options to continue anti-TNF therapy.
Thanks for the article.
I need to make a correction to my post: “One is a humanized mAb that has its heavy chain removed and is PEGylated so it lasts longer in the body.” It should be Fc portion not the heavy chain.
Yesterday my rheumatologist and I discussed point number 1. He specifically talked about the lack of response in some of his patients to tnf blocking biologics, myself included. He stated that the main problem is we are lumping so many diseases into one category for treatment and there is just so much that we still don’t know yet. Every persons disease is different and presents different is what he stated, so each treatment needs to be unique. A very interesting conversation with a doctor who has been practicing and teaching in rheumatology for over 40 years.
Thanks for the ad, it was interesting!
I have been on Humira for the past 6 yrs with very good results. And I have not been on steroids or methotrexate for over 16 years. I have tried other biologics Embril, stopped working and I lost my hair to Arava. Since I’ve had the disease since I was 19 and am 54 now, I’ve had to experiment with many things to find what works for me. Humira with a few other things plus being active does work for me. It all comes down to the fact that everyone’s biochemistry is different and what works for me might not work for someone else . And what works for them does not work for me. It’s all trial and error unfortunately. I’ve seen this while being on both sides of the fence for many years. As a practitioner and a patient.
I take Mtx and Embrel shots. At first, the shots worked great. 5 months later, not so much. I stopped taking them for 2 months because everyone around me was sick and I was afraid I would get sick. Well, I did get sick with bronchitis and then I had a anaphylactic reaction to the medicine for bronchitis. While I was in the hospital they figured out I had pneumonia and had to stay for IV antibiotics since I take immunes suppressing drugs. Well, what I’m getting to is that I started taking Embrel again after about 2 months and my rhuemy telling me to start to slow the degeneration going on. The Embrel is working great again. Has anyone else ever experienced this?
Becky, that is good news to hear that it is working great again. I often read comments of folks having problems with it working well again if they had to go off of biologics due to infections. I hope there are lots more out there like you! Keep us updated.
I think your point #1 is so very important to get out there to the public. I know this isn’t the first time you have brought up the total absence of the FACT that biologics don’t work for 1/3rd of us or more.. and so on regarding the real stats. As one of the 3rd I would like to say that if there is any way I can support you in getting this info recognized, please let me know. This is my most important cause and when I get a bit better I plan on starting communication to correct the misconception – starting with the arthritis org.
Anneke, I’d love to work together with you on that! Email me any time. kelly @ rawarrior.com
I would help in any way that I could as well. I have tried both Enbrel and Humira and neither one worked well for me. Didn’t have help from MTX either. None of the standard go to meds have worked with me. I tried to tell my rheumatologist that I am weird! I’m currently taking only medication for the pain and not anything to stop progression. My RA pain, fatigue and malaise is 24/7. I am hard to diagnose b/c I tested mildly positive for lupus, but negative RF. Very frustrating as my diagnosis has changed a couple of times, how can something w/out a definitive diagnosis be able to be treated with what is currently out there? But, I keep positive and would love to do what I could do advocate for those of us that have not had any luck with the commonly prescribed meds and fight for the research that we desperately need. 1/3 of a whole is enough to fight for.
I have been taking Enbrel and Mtx for ten years now and for the most part the combination works pretty well for me. The thing that really seems to set my RA off is if I get really sick with a virus or infection. It can take months for the drugs to really kick in again. My Rheumatologist says this is not uncommon.
Thanks for posting this research info Kelly. I have been taking Enbrel now for 2 years and it has been working great up till now. So I am getting ready to try a different one. I have been researching Humera and Remicade. This will give me more to think about and discuss with my Rheumy on my next visit.
Good to hear from you, Cammie. Good luck w/ the rheumy doc & finding a new treatment that will work great for you.
I’m on my 3rd biologic first was Enbrel, which I could tell worked pretty well, but, after a few months began to fade and my joint pain got worse and more symetrical. Then I went on expensive Remicade (expensive because you have to pay to have the infusion, not just a med you give yourself at home). I was not getting got response and my doctor kept upping the dose. It was getting out of control both the ineffectiveness of it and the infusion center cost. Now I am on Cimzia, just finished my loading doses, and I am worried about how well it is going to work when I go back down to the regular dose. I can tell it works for a few days really well (I still have a few really angry joints) but after that, the pain and stiffness starts to creep back up on me. I have continued to take MTX at 1 mL injection throughout all this. And 5 mg prednisone (I have tried to reduce the prednisone to no avail, my pain comes roaring back).Sometimes I wonder if these treatments are somehow incomplete in their form or chemistry. Or they need another type of drug other than mtx taken with them. More research!
To say the treatments are incomplete is a gross understatement. TNF is only one of several inflammatory cytokines. I’ve think that if anti-TNF therapy isn’t working for a patient initially then it is because the patient’s inflammation is not mostly mediated by TNF. Some other biological process is going on. TNF is a major player but it isn’t the only game in town. There are lots of new treatments in the clinic now from kinase inhibitors to other biologics covering a wide range of various biologies. Perhaps one of these will hit a home run and give us many more treatment options.
Hello Kelly..I just read Your column on Humira. I believe im the lucky one.I had to be off my Humira for 2 months.When i started back i was worried it wouldnt work but it has. So i guess im the lucky one.Well considering the cost.I know the solution for this is years away but i pray for those who do not benefit from Humira anymore.Hope they find somthing that works for them.Thanks again for what you do for all of us..Judi
Interesting! I wonder how accurate this is in peds patients. Jordan was on Enbrel then Humira. She did Humira for over a year, it kept her eyes quiet for a long time but her joints were never “normal.” She always had some slight swelling in a few joints and asked for pain meds a few times a month while on it. If she fails Remicade her rheumy wants to try Orencia. I hate putting these meds into her little body and I wonder what they’re doing to her. What does her future hold?? Are there studies about long term in with children? Am I really a bad Mom for allowing her to be on these meds? But what other choice do I have? Let her go blind and suffer?
AHH!!! Sorry for the rant, it’s so hard when I have to make these decisions for her. I hate taking these meds too but I’m an adult, I’m responsible for her well being. Knowing that I could possibly harming her is an awful feeling.
Long term studies would be going on now, but the treatments aren’t old enough to give that too you ahead of time. It must be so hard for you, Stacey. But you are hopefully helping her to have less damage from the disease – far from ideal & no guarantee, but you are a great mom & getting her the best care available! New JA guidelines (I’ve been working on a blog post) seem to be aggressive with treatment.
Oh I feel for you so much! Which is the lesser of the two evils? I don’t think that there are any long term studies on anybody with these biologics, much less studies on effects on children. You can only do what you think is best based on the information that you have and hope and pray that it is the best choice. And I wouldn’t think that you should second guess yourself either. I so feel for you, I would more than likely make the same decision based on what RA can do over the span of a lifetime to so many parts of the body. Please don’t beat yourself up, you sound like a good and loving momma and must trust that your decisions are the best for Jordan. I have wondered what I would do if I had a child that had RA, lupus, or cancer (some disease where the treatments are almost as hard as the disease itself) but I think that I would do whatever I could to make them as healthy as possible, as well as pain free as possible. I will be thinking about you and Jordan for a long time as your post really touched my heart!!
Thank you Kelly and Dawn. We’ve sat down and thought long and hard about the meds and what they might do to her. We decided the benefits outweighed the risks. I know these meds have black box warnings but if we didn’t treat her she would be blind and unable to walk. We’ve chosen to give Jordan the best childhood we can based on what God has given us. Her quality of life is so much better then it would be if she wasn’t treated. And that really is all that matters.
My experience with biolgics has not been the best. After being on Remicade for 8 months with methotrexate my doctor switched over to Orencia with methotrexate, for which I have been on for a year.
To be honest I think both meds may have helped a litte, but not enough to stay on them. I have daily flare ups now and I am hesitant to say anything to my doctor because he has already told me that Rituxan is the next biologic he wants me to try.
I have been diagnosed with RA for about 6 years now and despite the ladder of meds, I still have joint deformity and flaring.
I just wish I could achieve a better level of wellness.
Hi, I have RA ,and I am currently taking Humira injections, However i have just been tested possitive for epsteinbar virus. Does this go hand in hand with Humira? because of the immune system. should I stop the Humira?
Thanks
MyLissa
Over the last few months I have had drenching sweats right through the day, my blood tests have shown the development of auto-antibodies. I have been on Humira & Methotrexate for about 4 years. I have been experiencing an increase in pain also. Is this because of the anti-bodies?
I forgot to say I am 74 and have had RA since I was 35.
Hello,
My doctor had me tested to see if I was developing antibodies to Humira and my insurance company has denied paying for the test. They claim that it was not medically necessary and not a proven or reliable test. Have you heard of this before and is this test considered valid? The test costs $2500.00 so I plan to appeal the denial, any information would be helpful.
Regards.
yes, I had heard that antibodies can be tested, but not that it was so expensive or that it is controversial.
Can you get the name of the test they did and search for articles online that show it’s valid. I know your doc must know how to show it’s a valid test—since it was offered at a lab.