Rheumatoid Arthritis- crystal ball gazing

Let us look at a hypothetical situation today. I’ve just diagnosed a patient to have Rheumatoid Arthritis. I ask for some specific investigations. A few of them are genetic markers, others cytokine biomarkers. I send a sample for protein biomarker microchip analysis. The patient walks into the clinic a week later. I click on the system, his reports are already in & there you go—-I can look into the future…..

The system gives me all the answers:
1)Is she going to have an aggressive disease?
2)Will she respond to methotrexate? Leflunomide?
3)Will she do well with the basic DMARDs or she would require a biologic agent?
4)If yes, which is the biologic agent she is most likely to respond to?

Great! Work done! The best I can expect to have for a patient. With advances in basic sciences & technology, this situation can be envisioned in the near future.

We already have a few clues:
1)Anti CCP antibody definitely gives us a clue to the aggressiveness of one’s RA.
2)HLA-DRB4 (a genetic marker) does help to know the aggressiveness of one’s RA.
3)We do have a few genetic markers to predict responsiveness to Methotrexate. However, they have been studied only in the Dutch patients till date.
4)There are a few biomarkers to help predict response to Enbrel.
5)Again, we have a few markers to help predict response to Rituximab (Rituxan/ Mabthera).

We have still not perfected the said markers & techniques, but what we know for sure as of now is:
1)RA has to be treated with a combination of DMARDs instead of a single drug.
2)RA requires aggressive management right from the beginning for a better outcome down the line.
3)No RA (even seronegative RA) should be underestimated as mild RA & taken lightly.


25 Responses to Rheumatoid Arthritis- crystal ball gazing

  1. RA SB says:

    Dear Dr.,

    This is a great post, though I am confused b/c my Dr. has never used a similar program for my diagnosis. Is this something not available yet in the US?

    Also, I have seronegative RA, and I have read that as a characteristic, seronegative RA generally attacks the larger joints. I have found this to be very true for me. I am lucky in that my hands, while sometimes sore, are not badly affected by the RA. However, my knees, shoulders, elbows, and ankles are very tender and swollen. I honestly think that larger joint RA is more painful (since I did have hand RA the first year before it moved to my larger joints). Also, my first dr. was Dr. Robert Lahita in NYC. He has published much on the subject of autoimmune diseases, speicifically lupus. Do you know him? He once told me that sometimes seronegative RA was the worst he has ever seen. This seems true for me.

    In any case, I was just wondering how come I had not been exposed to such software. And I wanted to thank you for the hint about the vitamins.

    One more thing. I have been hearing some wonderful things about AP therapy from some RA sufferers, but I know docs don’t generally buy into this theory. Could you tell me your thoughts about trying this therapy. Thank you.

    RA SB

    PS. I am making you my next “link of the week.” 🙂


    • Dear RA SB,

      This program does not exist as of now. But, I’m sure we would have something of this sort very soon. We are steadily advancing towards sufficient scientific evidence to develop investigations and a software to look into the future of a RAer.

      Thanx for choosing me as the l’ink of the week’!


  2. Rheumatologe says:

    The new EULAR/ACR criteria are based on what you have stated clearly and elaborately. Thanks for this blogpost.
    The last EULAR congress at Rome acknowledged these findings/data.
    Aggressive therapy is a must in an aggressive disease.


  3. RA SB says:


    I finally add ya as the link of the week. Hope I send some traffic to the site. I find it helps me understand a great deal. 🙂

    – RA SB

    BTW, would you agree with my rheumy’s assesment that we try the last 2 biologics before moving on to AP? Just curious as this was one of the hardest decisions to make.


  4. Jene Ocon says:

    I very much like your blog. Great content. Please keep posting such great cotent.


  5. RA SB says:

    Hey Doc,

    AP stands for “Antibiotic Protocol.” I was getting frustrated because I had failed every TNF inhibitor, had initially responded to Orencia (75%), but later it stopped working after briefly stopping it to try to conceive. I was getting disheartened with the biologics, plus I had been on mtx for five years, and had lost almost all my hair. So I was all set to go with AP, but my doc talked me in to trying Rituxan. I SO want it to work. Also, she gave me Arava. I hear there can be hair loss with that too. Is it as bad?

    Thanks Doc – You Rock.
    – RA SB


    • Rituxan is a good agent. As against other biologics, 2 doses have a sustained effect for 1 to 2 years. It is definitely worth a try.
      Arava is a good drug too. Though, it may be a tricky drug if you are trying to conceive. There can be hair loss with methotrxate as well as arava. Biotin (a viatmin) does help take care of the hair loss. You can speak to your Rheumie about it.
      All the best!


  6. Kym says:

    Really great summary of what I’ve cobbled together about the current status, and you have a way of presenting it that conveys respect and concern for your patients.

    I was diagnosed recently with RA (pos RF, pos anti-cpp, elevated ESR) (was palindromic for a year) and started Methotrexate a couple of weeks ago. I haven’t read anywhere else that more than one drug should be used. What, in addition to Methotrexate should one add? Or should I wait a few months to see if the Methotrexate alone is sufficient?


    • No. One should not wait to see if a single drug acts. The basic minimum is 2 drugs right from the beginning & aim for remission asap rather than wasting time in seeing the response to a single drug. Remember that time is equivalent to function in RA. One should waste minimum possible time to preserve maximum possible function.
      We have learnt this the hard way. Previously Rheumatologists used to have a ‘wait & watch’ policy & a stepwise approach. That amounted to watching the patients evolve & worsen over time. However, recent studies have clearly showed that RAers have to be started on a combination of drugs & remission aimed at asap.
      The usual combination is methotrexate & hydroxychloroquine. However, this is a matter of personal choice.

      Hope U conquer Ur RA,
      Dr. S. M. Akerkar.


  7. RA SB says:

    Hey Doc,

    Glad to see traffic picking up! I started the biotin after you told me a month ago. Seems to be helping, but also I stopped mtx. Just started arava. We are no longer trying to conceive. We have one child, and as I am now older (and sicker), we feel my health and his happiness are our number one priorities.

    Rituxan infusion tomorrow. Let you know how it goes.

    – RA SB


  8. Nora says:

    Thank you so much. Are there any over the counter DMARDs,or any vitamins that could stall this process/ I’m losing function by the minute.


  9. Nora says:

    Thank you again for your prompt response. Unfortunately, I have a swan neck right wrist,and my thumb broke backwards in January, so I haven’t been able to work as much as I’d like. (Apparently nobody wants a one-handed waitress)The rheumatologist wants much more money than I’ll ever be able to earn, so I’m going to be stuck saving up for a while. Thank you again for your help. Please keep doing all you do, it means so much.


  10. sara says:

    Hello! Thank you for replying to my post on RA Warrior, i have just a few more queries, then won’t bother you again hopefully for a while!

    I saw my new consultant on Tuesday. The appt was mixed with depressing but positive news. Firstly being a new consultant he wanted to make a good first impression and secondly he seemed very thorough and focused on moving my RA into remission by now introducing Embrel in about a month but i have to go through quite a process in order to receive this on our NHS.

    I have the RA factor, he said its an aggressive form, but i generally feel a bit better. I still have quite a lot of stiffness and occasional weekly flare and still need 2 x diclofenac a day (with Ranatadin) and i know the aim is to get me off these, my CPR is pretty high (60?) and he wants that to come down.

    I have been on Sulphasalazine for 5 years – which has worked v well but has now stopped working, – i now take a reduced dose of sulph and MTX for 7 months – building up from 7.5 in feb to 20 mg in the last 2 weeks.

    My questions (which i didn’t manage to ask as had so many others) are; a) have i given the MTX enough chance at 20mg to react?, b) will there have been any damage done in the last 7 months whilst waiting for the MTX to build up and c) do you think that my previous consultant ‘dragged his heels’ a bit over the last 7 months – ie should it have gone up quicker and suggested Embrel sooner? oh, and also d) what are the biomarkers that suggest that Embrel will be suitable for someone? – Soz for all the q’s! Lets hope this blog posts this time!


    • Dear Sara,

      Good to see that you are back to a positive frame of mind.

      Shifting to methotrexate from sulphasalazine (when it is not working) is a systematic step indeed. But, as I pointed out earlier, i would have started 2 DMARDs right at the beginning & tried to manage RA without diclofenac.

      The stepping up of the dose of methotrexate is also systematic but could have been faster. All recent studies point out to a rapid followup & faster escalation of doses to achieve remission.

      Presently there are no proven biomarkers for predicting response to enbrel. As mentioned in the blogpost, there have been a few studies looking at such biomarkers but we do not have anything concrete with us as of now.

      But, enbrel is a very effective drug & i hope you see your RA in remission with it.


  11. Nora says:

    Has anyone else heard about massive doses of zinc killing immune systems? Might this be used to tamp down or relieve flares?


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