Predicting Response to Rheumatoid Arthritis Therapy | Rheumatoid Arthritis Warrior

Predicting Response to Rheumatoid Arthritis Therapy

The problem of varying responses to RA therapy

Alpaca fenceIf you’re following comments on the blog, Twitter, or Facebook, you might have noticed some patients recently have been told by their doctors that that likely don’t have RA because they have not responded well to TNF-a therapies. Sometimes, this comes after a few years of RA treatment.

My treatment doesn’t work on your disease, so you’re not sick.” Maybe that comes from listening to the commercials. We need to keep the focus on the patients and find therapies for their diseases; it won’t work the other way around

Unfortunately, TNF-a inhibitors don’t work on everyone who has RA. There are logical explanations for this – other than the ones patients often hear:

  1. You must not have RA.
  2. Your tests look better so it’s working fine. Maybe you’re just depressed.
  3. You must have Fibromyalgia Syndrome (FMS), chronic pain syndrome, or something else.

Science will eventually catch up with the experiences of RA patients and explain a lot of things. The shortest road to understanding and predicting response will be merging clues from three key sources:

  1. What patients experience with the Rheumatoid disease (such as functional loss or pain).
  2. Genetic patterns in patients with RA.
  3. Scrupulously tracking what is physically happening to RA patients. (See below.)

One step closer to predicting response to TNF-a therapy


A recent Taiwanese study in Arthritis Research and Therapy describes “Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-alpha therapy.” Those who responded to the TNF-a blocking therapies had significant decreases in IL-17 and anti-CCP levels. “Serum levels of IL-6, IL-21, IL-23 and TNF-α were also significantly decreased after anti-TNF-α therapy in responders.”


However, in non-responders, levels of “circulating Th17 cells and IL-17 significantly increased” while TNF-a levels decreased after TNF-a therapy. As has been seen in other studies, Rheumatoid factor did not change significantly in either responders or non-responders, showing it’s a poor indicator of response to therapy.


It will be an incredible step to identify which patients may respond to which treatments. We aren’t there yet, but this clue points to what’s to come: “Multiple logistic regression analysis showed that only a high baseline IL-17 level (≧40.0 pg/ml) could significantly predict a poor response to anti-TNF-α therapy (p<0.01), with medium level of specificity (83.3%) and sensitivity (66.7%).”

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Kelly O'Neill

Kelly O'Neill (formerly Kelly Young) has worked about 12 years as an advocate helping patients to be better informed and have a greater voice in their healthcare. She is the author of the best-selling book Rheumatoid Arthritis Unmasked: 10 Dangers of Rheumatoid Disease. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. She is the president of the Rheumatoid Patient Foundation. Through her writing and speaking, she builds a more accurate awareness of rheumatoid disease (RD) aka rheumatoid arthritis (RA) geared toward the public and medical community; creates ways to empower patients to advocate for improved diagnosis and treatment; and brings recognition and visibility to the RA patient journey. In addition to RA Warrior, she writes periodically for newsletters, magazines, and websites. There are over 60,000 connections of her highly interactive Facebook page. You can also connect with Kelly on Twitter or YouTube, or LinkedIn. She created the hashtag: #rheum. Kelly is a mother of five, longtime home-schooler, NASA enthusiast, and NFL fan. She has lived over fourteen years with unrelenting RD. See also https:/

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12 thoughts on “Predicting Response to Rheumatoid Arthritis Therapy

  • August 22, 2011 at 7:36 am

    humm, very interesting. I know that my rheummy had me last December that 30% of RA patients do not respond to the biologics. This article does give hopoe that specific treatment per patient is going to possible in the future, maybe not my future, but for future generations. Thank you for all of your hard work Kelly, God Bless

  • August 22, 2011 at 9:08 am

    If failure of TNF therapies precludes one from having RA, why then is starting Actemra therapy based on failure of one or more TNF therapies?

    • August 22, 2011 at 2:49 pm

      good question Joe

  • August 22, 2011 at 9:18 am

    I feel the article is right on. Except there are those of us where the TNF blocker worked,but the side effects were not worth it. For me, they caused my lymph nodes to swell astronomically and unexplainable weight gain. With the “cancer” gene that looms in my gene pool as well, I refused risking the chances of lymphoma. But my doctor’s reaction was “don’t you want the quality of life?” When I said that I was going to fight this to raise my daughter instead of her burying me, he looked at me very stragely. He then told me by my blood count that I looked to be in remission, then I asked him why it still took me 30 minutes to get out of bed in the morning and why at the end of a school day teaching was I screaming in pain. He then sent me for many tests since he thought he had mis-diagnosed me. A week later, his nurse practitioner had to drain my knee of excess fluid and she kept saying she was in shock over the doctor’s comment. She said that it was definately RA by the color of fluid and she had never drained so much fluid from someone’s knee before. Now this doctor is limiting his practice to 600 and doing a wellness study. I am looking now to take my “pain” somewhere else. But being now on disability and waiting for medicare to kick in, I may be bak at having one of the Marz brothers as a rheumy. As I have always said – instead of saying “walk in my shoes” to doctors, we need to be shouting at the top of our lungs “walk in my pain!”

    • August 30, 2011 at 9:08 am

      GREAT response. As a cancer survivor and RA patient I am with you. I have found nothing works for long for me. Never have been in total recission from the RA. I am beginning to feel the doctor is “tired” of me. Do I change doctors? Hate to start all over again! I just want relief from the constant pain in my joints or what’s left of them. Have had both knees replaced and joint at base of thumb. I want to enjoy my grandchildren without swelling and pain!

  • August 22, 2011 at 9:19 am

    Thanks Kelly! While I haven’t been told I don’t have RA (I have some relatively severe deformities because of RA) I have been told I’m not in an RA flare, must be a fibro flare. Drugs either don’t work at all or stop working pretty quickly. It’s nice to get a little validation!

  • August 30, 2011 at 9:10 am

    Wow… The more I hear about some of the experiences people have with their Rheumy and other members of their medical team, the more I realize how lucky I am…

    When I was first diagnosed and I started talking to my Rheumy and his staff and then to people on the Arthritis Foundation’s RA Blogs, I was warned that RA was a weird disease. That there was no one-size-fits-all treatment or even a one-size-fits-most treatment. I was also told that the blood tests were sometimes tricky to read and some people were hard to diagnose because there was no definitive test that always diagnosed RA or not. I guess I was lucky that my tests and the pathology done on some “brown gunk” taken out of my knees in surgery left no doubt. I have RA… But taking all that I was told (and read many places online) about RA, why then is it that some doctors would say “you didn’t respond to ___, you must not have RA”? Sounds illogical to me…

    Wish everyone was as lucky as I have been with their medical team.

    Be well…

  • August 30, 2011 at 10:32 pm

    Good post! It amazes me how far and fast we are moving toward being able to test for which treatment to use. It will be nice for those who will not respond to not have to go through the trial-and-error period of disappointment.
    On a side note: I cannot believe a Doctor would assume that someone must not hava RA because they did not respond to the existing therapies. If they were the definitive answer, researchers would not be struggling to get new treatments out there.
    Thanks for keeping us all informed!

  • September 5, 2011 at 7:32 am

    Thanks a lot for this.

    I just stumbled upon this blog while searching for exactly this kind of thing – to see if there are other people who don’t respond well to the usual regime of DMARDs.
    I’ve been on Arava, Methotrexate and Enbrel over the past six years, and so far they’ve all failed to work properly for me.
    I was then told that I must have fibro, and medicated for that, which (surprise, surprise!) did nothing either.
    I’ve also been told it’s all in my head and that I must be lying about taking my medication, because there’s just NO WAY the meds are at fault here.

    I’m now in the process of trying to convince my specialist that it’s not that I don’t have RA, or have something else as well, it’s just that it’s treatment resistant.
    I had a meeting with her today, and we finally seem to be making some progress, which is great, but it’s frustrating that it’s taken so long.
    You’d think specialists in such a variable disease would be willing to accept that it might react differently to medication.

    Thanks again for this (and other) posts. I look forward to reading more. (:

  • March 4, 2012 at 7:45 am

    What would the level of confidence patients should be happy with?
    I guess it should be high percent right when predicting response but what level of error should be OK for it to predict one should go to alternative treatment then Tnf alpha when no other path is available but biologics.
    As patients should have a say…..
    How do one balance the suffering and loss of time to the chance to loose good therapy?

  • February 21, 2016 at 10:00 pm

    I can’t believe how familiar this sounds!
    I was diagnosed just over ten years ago, and have tried multiple RA meds with very little response. I did have temporary improvement from Humira, Actemra, and Remicade, but they soon became ineffective. My two prior rheumatologists didn’t seem to think it was all that unusual, and just kept trying. We talked openly about the difficulty of differentiating between non-response and incomplete response.
    So, as of 2016 I had to see a new (another) rheumatologist due to insurance changes. After reviewing my history, he asked “why do you think you have not responded to all of the different RA medicines”. As a retired RN with advanced credentials, I assumed he was extending professional courtesy by soliciting my opinion. Then he interrupted and restated the question, but this time I detected something suggestive in his tone. I later had trouble explaining his attitude to my wife; I could swear he was accusing me of dishonesty…but not quite.
    After reading this, I think I know what he was trying to elicit: he doesn’t think I have RA but wanted me to offer that opinion. Dammit!
    I am still taking my Stelara, waiting to see if it helps. I do have a follow-up appointment in March, and I look forward to it.

    • February 23, 2016 at 11:45 am

      Hi Scott,
      I hope you can update us after the appointment.
      Of course you probably know we’ve heard that before – some of us first hand and some from others.
      The sad part is as long as doctors blame the patient or doubt the need for treatments, the worse the damage is and the less the chance for remission due to wasted time.
      By the way, I always take someone with me, so if there is a dismissive, accusing attitude, I have a witness at least. It helps me know I’m not imagining it. Plus hearing it from other patients helps me know it’s not my “fault” if they act like that.
      It reminds me of a fellow we call Dr. No


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