Affective Error

Last year, MedPage Today‘s John Gever wrote a piece for ABC News titled 25 Years in Arthritis: New Treatments, New Hope.  After glowing reports on the promise offered by multiple DMARDs and BRMs, how much better the prognosis is than it used to be, new treatments, new hope, ray of sunshine, rah-rah-rah, buried at the bottom of page three we find:

Life is still not a bowl of cherries for RA patients. Eventual disease progression remains the rule for patients, even though, compared with earlier generations, they will be much older when joint surgery becomes their best option.

WHAT!?  I was shocked when I read this.  Disease progression remains the rule?  But… but…

Aggressive management can improve function, stop damage to joints as monitored on X-rays, and prevent work disability. (MedicineNet)

Disease-modifying antirheumatic drugs…  can slow the progression of rheumatoid arthritis and save the joints and other tissues from permanent damage. (Mayo Clinic)

Strategies are all aimed at reducing pain and discomfort, preventing deformities and loss of joint function, and maintaining a productive and active life. (Johns Hopkins)

The goals of treatment with rheumatoid arthritis medications are to achieve remission and prevent further damage of the joints and loss of function, without causing permanent or unacceptable side effects. (UpToDate)

Early diagnosis and treatment of RA is critical if you want to continue living a productive lifestyle. Studies have shown that early aggressive treatment of RA can limit joint damage, which in turn limits loss of movement, decreased ability to work, higher medical costs and potential surgery. (Arthritis Foundation)

It’s so easy to hear the promise of how much better things are now than they used to be – to focus on the hope and promise of better treatments.  After reading that depressing little statement buried in the 25 Years article, I went back and re-read the RA articles previously referenced:

The optimal treatment of RA requires a comprehensive program that combines medical, social, and emotional support for the patient. It is essential that the patient and the patient’s family be educated about the nature and course of the disease.  Strategies are all aimed at reducing pain and discomfort…  (Johns Hopkins)

Medications can reduce inflammation in your joints in order to relieve pain and prevent or slow joint damage…   You may need stronger drugs or a combination of drugs as your disease progresses. (Mayo Clinic)

…the goal of treatment in rheumatoid arthritis is to reduce joint inflammation and pain, maximize joint function, and prevent joint destruction and deformity. Early medical intervention has been shown to be important in improving outcomes. Aggressive management can improve function… (MedicineNet)

I’ve been wondering how I could have so easily missed the warnings all these articles hold.  Last night, I might have found the answer.  I’ve been re-reading Dr. Jerome Groopman‘s How Doctors Think:

We all tend to prefer what we hope will  happen to the less appealing alternatives; this natural tendency is termed “affective error.”  We also lull ourselves into thinking that what we wish for will occur when we get the first inkling, however fragmentary, that our wish may come true.  In short, we value too highly information that fulfills our desires.

It reminds me of the discussion I had with my rheumatologist when she recommended adding a TNF-blocker.  I’d heard such wonderful things about biologics, but I questioned her, “So this will stop the joint swelling?  I’ll get my life back?”  Maybe.  That’s the goal.  No promises.

I highly recommend Dr. Groopman’s book, How Doctors Think
Another book, Anatomy of Hope (written with cancer patients in mind) is also pretty good

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25 thoughts on “Affective Error

  1. Thanks for this post. Maybe it just appeals to my cynical nature. Skeptical nature. Whatever you want to call it. I do have a good rheumy (my second = after I fired my first for not being aggressive enough, amongst other things). But I think she’s fallen prey to this affective error too. At least according to an article she was co=author on with some of her colleagues several years ago. I think they had a mantra, “elimination of synovitis equals elimination of joint destruction.”

    I don’t know how many times I’ve wanted to bring this up to her and tell her that I just don’t feel it’s true. That damage continues. I don’t, I suppose, out of deference to her and because I like her. The situation is not all her fault – I could’ve tried biologics earlier, when I had insurance. But part of why I didn’t was that I seemed to think those should be used on the really severe cases and because their side effect profiles and long term effect profiles are not well established yet. It’s not like she never offered those. But she never pushed either. Probably thinking along the same lines somewhat.

    But here I sit with progressive damage that will definitely require surgery and/or replacement probably before I’m fifty. We skirt around the issue and I say oh, I’m sure some of this progression is mechanical and she nods in agreement but making a point of it for the fellow to note and not saying much about what I added that I do think some of it is still active disease. I only hope she is more aware that there is still synovitis going on (it is more obvious to the eye now again that it was a couple of years ago).

    But (another but) gosh, I know we’re trying to save costs, and I don’t have insurance for it at the moment, but when I did, she could’ve said let’s run some more tests to see if you are still having something going on or if you are really in drug induced remission or not. Another SED, anoter CRP, an xray, ultrasound or MRI. I’ve not had many of those. Let’s just do that so we can see if keeping the status quo of meds combo is still right for you or should we really consider the biologics more seriously and sooner. Let’s see if our mantra is really true.

    Well, yeah, but the more I read about those biologics, they only work for roughly fifty percent, and though they may slow things, there is still sub=clinical inflammation going on as seen in ultrasounds and MRI’s. There is an uncoupling of inflammation and joint damage. That the triple combo of the old dmards is doing about as well as the new drugs. So much promise, but we still don’t seem that far progressed. Except some of us may be able to work a few years longer, which is good for society overall. Gotta help pay for that Medicare ya know. Oh well, thanks for letting me ramble on to nowhere. Sometimes I wish I could just blindly follow hope, but I always want to know the ins and outs of it all if I can and understand it to the best of my ability. I believe in stating it for what it is and not sugar coating it.

  2. Sorry for the partial first post. anyway, I always knew I wasn’t in true remission because I still had and have a lot of pain. I think she was trying to write it off to fibro, though she never said so, even when I queried her about it directly she didn’t respond to it. I get frustrated in trying to relate these things to my docs. They know I have had a stressful life otherwise and aside from the RA and I think they write a lot of it off to that and I wish they wouldn’t!

    Edit: I’ve accidentally posted comments before I meant to, too. Not a problem. I deleted the partial

    • Wow, little pitty party I had there, huh? If anyone is wondering, a good amount of my pain is at least what I perceive to be tendon and bursitis related, and my flares often start this way, so it doesn’t always present as frank swelling.

      • I didn’t take it as a pity-party at all. I can’t imagine knowing that a different med might help but there’s no way to afford it. Are you on combination therapy?

        My rheumy orders ESR/CRP/etc every time – but the results are meaningless. I maintain that there is inflamation that is not measured by those tests and it’s high time for more discoveries/advancements to be made.

        I think I read that biologics help around 70% of people; I’ll try to see if I can find hard data.

        You might see if your public library has Anatomy of Hope. The author distinguishes between pie-in-the-sky wishful thinking, and hope tempered by reality.

        I’m sure there are other points you made that I wanted to respond to, but I’ve been up 18 hours after not much sleep and am starting to ramble.

        • That probably is a book worth going and finding to read. Maybe one of these days if I get the energy, I’ll go hunt it down.

          The only dmard I am on now is methotrexate. And prednisone, along with piroxicam and tylenon arthritis strength. At one point, while on insurance several years ago, I did try adding Kineret shots to the methotrexate, but stopped it after several months because I could not tell that it was making any additional difference and because the pricing by insurance was odd (in amounts allowed per 28 day month if I recall) and was still going to be very expensive.

          I took prednisone and the antibiotic doxycycline my first year under the first rheumy. He did not want to start me on methotrexate for some reason. In hindsight, this was perhaps because my albumin level was slightly under normal level. He may have thought that I would have side effects. Or maybe it was because I was young and still of potential child bearing age. Who knows, because he never said why. Just that he didn’t want to put me on methotrexate. I think he mentioned Arava fairly early on, but he never did prescribe it. Heck, he never told me I had RA until I demanded to know what was going on with my wrists and hands and feet and why did I feel like a 90 year old when I was only 30. So anyway, I fired him, with a nice long letter.

          I then moved to new rheumy who started MTX. It was working pretty well, not perfectly, but pretty well. Then an incidental finding, that we didn’t know if was due to the MTX, or the RA itself, or something else entirely. So stopped the MTX for a couple of years. Took immuran, then added Arava to that. Got some precancerous skin lesions that got me nervous, so after time with lots of research on the potential MTX effect on the incidental finding that fortunately resolved and I decided wasn’t due to the MTX, I decided to restart the MTX two years later. Much damage ensued joint wise in those two years.

          I have looked at plaquenil, and almost added it to MTX once, but have a history of macular degeneration in the family and so haven’t, although perhaps that’s a small risk, it’s still there and I have a thing about losing my signt. I cannot take the sulfasalazine (sp?) because I’m allergic to sulfa drugs (exfoliative dermatitis – which could potentially be Stevens-Johnson Syndrome). Although I did discuss with current rheumy one time about maybe going to an immunologist and trying desensitization to it, and she was willing to find me an immuno doc to discuss this with. But I hadn’t proceeded on that before I lost insurance.

          I do get envious when I hear of RA’ers on Enbrel who get so much energy. I think of it often when I think of the fact that I’ve got to get off this prednisone after a decade or more of being on it. I cannot get through my work day or take care of two family members (one mentally disabled and one physically disabled) without the prednisone. My rheumy seemed to think Humira would be a good one to try. I wonder if it gives as much energy as Enbrel.

          Well, I’ve written more than I wanted to this late. I would like to get a discussion going on the effectiveness of the biologics – what percentage are helped by them, and how well do they really work. I am into this tangent of the uncoupling of inflammation and joint destruction, particularly with the biologics. Want to know if the mantra, “elemination of synovitis equals elimination of joint destruction” rings true – because I don’t believe it does, from my personal perspective and from some things I’ve read. I think it’s affective error. Yes, we need new markers of progression and remission in RA.

        • WS – In terms of the 70%, I think what they are referring to is that 70% achieve an ACR20 response on these drugs.
          In these trials they like to measure how many patients in each group reach either an ACR20, ACR50, or ACR70 response, in addition to other types of measures like the DAS28, radiologic xray scores and such.

          I’m not a doc, so I can’t explain ACR responses in detail, though that exists somewhere on the net and on ACR’s site I’m sure. That’s a topic for another day. But here’s how I’ve simplified it in my mind and I hope it doesn’t do too much disservice to the concept, after all they have to have measures of some sort to go by. I see it as being a response of improving your overall complaint level or feeling of well-being, or of feeling some percentage of your old normal self. So I see an ACR20 response as being only an improvement of my overall RA situation of 20%, (50% for ACR50, or 70% for ACR70). Someone can correct me if I’m wrong, please. I cannot state at this moment without looking it up what all the ACR response criteria are, or how they compare to the other measures generally looked at in these clinical trials, so this is probably a way over simplification.

          In these trials, in terms of the ACR response level, and ACR20 would be considered a minimal response and anything under that is considered a non-responder in terms of that measure anyway. If you ask me, 20% isn’t much of a response, but hey, I guess it’s better than nothing. I’m more interested in getting a much better response rate than that! But that’s where we sit with these drugs – they are not an overall magic pill for most, and most cannot stop them without relapsing so to speak. Sure 70% achieve some level of response, but only about half achieve the higher responses of ACR50 and even less achieve ACR70. This if I recall from my reading has been what has occurred with most of the TNF inhibitors anyway. I don’t see 70% of patients only getting a 20% improvement as a huge breakthrough.

          Below is from a paper looking at the current biologics and other meds in the pipeline. Unfortunately it did not mentione ACR50 and ACR70 responses for Enbrel or any of the other biologics except for Humira (which did however, perform much better than MTX alone):

          “The ARMADA trial, a 6 month placebo controlled,
          phase II/III study with 271 enrollees, demonstrated significant reductions in the signs and symptoms of RA, improvement in physical function, and the safety of adalimumab (HUMIRA) plus MTX vs placebo plus MTX. At 24 weeks, the combination treatment arm (adalimumab plus MTX) had significant higher ACR responses (ACR20: 67%, ACR50: 55%, and ACR70: 27%) compared with 15%, 8%, and 5%, respectively,in patients who had received placebo + MTX (P  0.001).18

          In conclusion, adalimumab demonstrated significant and
          sustained reduction in signs and symptoms, inhibition of radiographic progression, but and also improved functional status,quality of life and work productivity in patients with RA.”
          The paper can be found here. Just skim over the hairy parts and read the beginning and ends of each sections if you can’t stay awake to get through it all.

          “Biological targets in the treatment of rheumatoid
          arthritis: a comprehensive review of current
          and in-development biological disease modifying
          anti-rheumatic drugs”
          http://www.dovepress.com/articles.php?article_id=3581

          The following abstract was an effort to try to compare the biologics to each other based on ACR50 results, but makes note at the end that it is difficult to compare the studies head to head. Also, no single study has compared the biologics head to head that I’m aware of.

          “Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007848.

          Biologics for rheumatoid arthritis: an overview of Cochrane reviews.
          Singh JA, Christensen R, Wells GA, Suarez-Almazor ME, Buchbinder R, Lopez-Olivo MA, Tanjong Ghogomu E, Tugwell P.

          Medicine, Minneapolis VA Medical Center, 1 Veterans Drive, Rheumatology (111R), Minneapolis, MN, USA, 55417.

          BACKGROUND: The biologic disease-modifying anti-rheumatic drugs (DMARDs) are very effective in treating rheumatoid arthritis (RA), however there is a lack of head-to-head comparison studies. OBJECTIVES: To compare the efficacy and safety of abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab in patients with RA. METHODS: This ‘Overview of Reviews’ was done by including all Cochrane Reviews on Biologics for RA available in The Cochrane Library. We included only data on standard dosing regimens for these biologic DMARDs from placebo-controlled trials. The primary efficacy and safety outcomes were ACR50 and withdrawals due to adverse events. We calculated Risk Ratios (RR) for efficacy, Odds Ratio (OR) for safety and combined estimates of events across the placebo groups as the expected Control Event Rate (CER). Indirect comparisons of biologics were performed for efficacy and safety using a hierarchical linear mixed model incorporating the most important study-level characteristic (i.e. type of biologic) as a fixed factor and study as a random factor; reducing the between study heterogeneity by adjusting for the interaction between the proportion of patients responding on placebo and the duration of the trial. MAIN RESULTS: From the six available Cochrane reviews, we obtained data from seven studies on abatacept, eight on adalimumab, five on anakinra, four on etanercept, four on infliximab, and three on rituximab.The indirect comparison estimates showed similar efficacy for the primary efficacy outcome for all biologics with three exceptions. Anakinra was less efficacious than etanercept with a ratio of RRs (95% CI; P value) of 0.44 (0.23 to 0.85; P = 0.014); anakinra was less efficacious than rituximab, 0.45 (0.22 to 0.90; P = 0.023); and likewise adalimumab was more efficacious than anakinra, 2.34 (1.32 to 4.13; P = 0.003).In terms of safety, adalimumab was more likely to lead to withdrawals compared to etanercept, with a ratio of ORs of 1.89 (1.18 to 3.04; P = 0.009); anakinra more likely than etanercept, 2.05 (1.27 to 3.29; P = 0.003); and likewise etanercept less likely than infliximab, 0.37 (0.19 to 0.70; P = 0.002). AUTHORS’ CONCLUSIONS: Based upon indirect comparisons, anakinra seemed less efficacious than etanercept, adalimumab and rituximab and etanercept seemed to cause fewer withdrawals due to adverse events than adalimumab, anakinra and infliximab. Significant heterogeneity in characteristics of trial populations imply that these finding must be interpreted with caution. These findings can inform physicians and patients regarding their choice of biologic for treatment of RA.”

            • Here is a paper (and a portion from it) discussing percentages for ACR50 and ACR70 responses, albeit between switching from one biologic to another. Roughly about 6-15% seem to achieve a “major” response upon switching from one biologic that is not so effective for them personally to another biologic.

              http://arthritis-research.com/content/11/6/R163

              ” In general, an ACR20 can be obtained in 60% or more of the poor responders to the TNFα blockers, and an ACR70-DAS remission value can be obtained in roughly 10% to 15% of the cohorts after the TNFα blockade, with either CD20 depletion or CTLA4 stimulation. The rule of a 10% to 15% gain of effect after TNFα, the major target, seems to be a good, but not ideal, perspective for the future of RA. These data strongly argue for a clear-cut need for biomarkers capable of identifying, at baseline, which RA patients having different pathways will be the best responders to some biologics or poor responders to other biologics. Yet these biomarkers are not at hand. Furthermore, prescribing a biological agent is an important decision that can greatly impact the quality of life of a patient and can be associated with varying medical costs, owing to differences in routes of administration (depending on the agent). Etanercept and adalimumab are administered subcutaneously. Both can be self-administered at home, but they have some disadvantages, including the requirement of more frequent administration and the risk of pain and local site reactions. Intravenous drugs can be inconvenient for patients with respect to traveling and taking time off from work for infusions and also for patients with difficulties regarding intravenous access. Intravenous administration may use more health care resources and require infusion rooms and equipment as well as medical and nursing supervision [20]. Anti-TNFα agents require a short time of administration to reach their effect, and anti-CD20 and abatacept have to compete with this very practical issue that needs to be considered when a choice has to be made to reach a major response. In addition, the more frequent administration with some TNFα blockers, required to better control the disease activity status, should lead to a careful analysis of cost in all of these situations.

              Conclusions
              The efficacy of different biological agents in selected randomized controlled trial populations is not similar in all patients, underlying the presence of different pathways driving the inflammatory process. The rescue to a major response seems to occur at a rate of 10% to 15% among the various biologics. Annual costs and administration modalities need to be taken into account when making therapeutic decisions in non-responders.

  3. Same happens with many chronic diseases. Sometimes I think docs believe progression is inevitable so some are not as aggressive as others. I’ve found this to be so very true of endocrinologists in regards to diabetes. Also rheumys in regards to any other of hundreds for forms of arthritis. Good posting!

    • There’s definitely a difference between the aggressiveness of my 1st and current rheumatologist. There needs to be a balance – false hope doesn’t help anyone, but neither does fatalism.

  4. Sigh.

    I think this is one of the reasons I have always avoided looking too far into the future, whether I’m thinking of my career or my personal life. Too scary.

    • I wasn’t trying to be depressing. It’s just so frustrating to have to search and search for reliable information, and discover that perhaps I’ve been overly optimistic.

      One day at a time. :)

  5. The key word to these promising stories about RA drugs is “can.” RE: Disease-modifying antirheumatic drugs… CAN slow the progression of rheumatoid arthritis and save the joints and other tissues from permanent damage. (Mayo Clinic)(my caps).

    They don’t say: “Disease-modifying antirheumatic drugs WILL slow …” precisely because RA is such a quixotic, changeable disease, symptoms and damage varying from one sufferer to the next. They cannot, in truth, write anything more than “can.”

    The fact is that RA is incurable. Even if it goes into remission (as mine did for many years) it remains locked into the body, waiting to awake again, and it continues to do its damage very subtly. So while it’s worthwhile to try these drugs in the hopes that they’ll slow the RA down and delay the damage it causes, the drugs aren’t cures.

    It would be good if doctors and materials that promote these drugs would be honest and say from the outset that they cannot stop or prevent the disease, its symptoms or its outcome entirely for the vast majority of people. But these drugs do hold out a modicum of hope. They DO help some people. Just not all.

    Great post, WarmSocks. Don’t let this discovery keep you from trying these meds (as I did, for a long time, out of disgust). You might be one of the small percentage of people with RA that they really do help.

    • Thank you. I caught the distinction between “can” and “will” but somehow I’ve tried to look on the bright side and hope for the best. It CAN make a difference, and I wanted to be one of the lucky ones. I guess I’ve been hoping that disease progress would be slowed until a cure is found. That’s quite different than slowing progress so that joints are replaced later instead of earlier.

      I, too, would like it if doctors would be honest about the disease. To tell the truth, I haven’t gotten much education about this from my doctors. I can’t say anyone’s been dishonest – they’ve been silent.

      Early results from Enbrel have me wondering why doctors don’t start a biologic immediately. I have tons more energy.

  6. I’m sitting here feeling, as I do at times, more than a little freaked out wondering if I’ve made the right choice of drug combo. I’ve decided to go with Methotrexate and a biologic right off the bat as WarmSocks suggests (in my case, Enbrel, which luckily was approved by my insurance company). I still haven’t asked my doctor if my case of RA is considered moderate or severe – despite wanting to know absolutely everything else about what’s going on, psychologically I can’t bring myself to have it labelled that way (and, really, what does that mean?? I still haven’t been able to pin it down anywhere).

    I suffer from migraines, too, and I learned through that whole trial-and-error process that sometimes one drug doesn’t work or the side effects aren’t acceptable, and then you move on to the next one. I’m hoping I hit the lucky combo right off in this case, and it prevents as much damage as is possible in the RA world right now. Let’s hope these two drugs work – fingers crossed!

    Laurie

    • Laurie, I see nothing wrong with trying that combo from the start and that is the way the thinking in the rheumy community seems to be going, as long as they can justify the cost. I just hope it’s not false hope manufactured by Big Pharm, or as Warm Socks writes, about just putting off the joint surgeries a few more years. We will not know unless newly diagnosed, early stage RA’ers are brave enough to act as guinea pigs. :-/

      Biologics were just getting into the swing of things when I was first diagnosed and I think docs were still a bit more cautious with them, probably less so now. In addition, “the incidental finding” kind of waylaid things for me in general (aside from cost) and has had me meandering in my RA treatment journey in an odd way, but this is not something too common.

  7. If you sit down and read through all the potential, but not necessarily inevitable side effects and the research and case reports, boy, it is a scary world we’ve been thrown into with our RA. I am sorry to scare folks when i do discuss potential side effects or complications, but I personally feel that education is the best “weapon” in our fight and in other’s fight with chronic conditions such as RA. But a better educated patient can make more informed decisions on treatment in conjunction with their doctor. I too have never asked that question directly but come to view my case as moderate overall. It’s not easy to predict anyway. I think we all have to get used to some level of second guessing ourselves, and sometimes our doctors, trying to strike a balance between skepticism and hope, but in the end, we all pray and cross our fingers and toes, that we’ve taken the right path regardless.
    Chelsea

  8. not such a pitty party… I kind of like the post… it is real. I personally love the math geek picture… I guess most of the time I try to be ‘real’

  9. @Laurie – I sure hope your med combo works for you. I’ve found that the Enbrel started working much quicker than hcq or ssz (my first two dmards). I’m looking forward to hearing how much better you’re feeling in the near future.

    @Chelsea – You bring up a bunch of points that I think I’ll address in some future posts.

    @alicorndreams – :) That’s one of my favorite cartoons. Glad you liked it, too.

  10. Computer Gurus – anyone know why about two thirds of my feeds would disappear? Windows IE. If I try to add the feed again, it acts like it’s already there but no link to it in my feeds list. Thanks for any help anyone can provide.

    • I’m no guru, so hopefully someone else will see this and answer. My feeds disappeared when I switched to IE8 – apparently they all go into their own folder now instead of my general inbox. You might search around and see if you have new feed folders.

  11. Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis
    Ai Lyn Tan 1, Steven F. Tanner 2, Philip G. Conaghan 1, Aleksandra Radjenovic 2, Philip O’Connor 1, Andrew K. Brown 1, Paul Emery 1, Dennis McGonagle 3 *

    http://www3.interscience.wiley.com/cgi-bin/fulltext/104530618/HTMLSTART

    ////There is a growing recognition in rheumatology that joint biomechanical factors, microtrauma, and injury may play an important role in the pathogenesis of early RA ([15-17]). Indeed, evidence for tissue microtrauma, as suggested by microscopic inflammation, in otherwise normal joints has been reported ([34]). It is likely that joint biomechanical factors exacerbate inflammation at sites of highest stressing, by undefined mechanisms. One possibility is that common molecular pathways linking the inflammatory cascade and cellular mechanical stress could be involved. For example, key proinflammatory transcription factors including nuclear factor B, and kinases including p38 mitogen-activated protein kinase, both of which are pivotal in the inflammatory response, are also regulated by biomechanical stress ([35][36]). Several other molecules share this dual property (for review, see ref. [35]), suggesting that biomechanical factors could contribute to the severity of synovitis and the degree of erosion. Furthermore, the higher biomechanical forces at these sites could contribute to increased oxidative stress, thus exacerbating inflammation and damage ([37]).

    It has long been considered that the progression of erosive disease in RA may be, to some extent, independent of synovitis, an observation that is supported by findings in clinical trials in RA, in which it has been shown that suppression of synovitis does not necessarily halt erosion ([38][39]). Consequently, it has been suggested that synovitis and erosion are uncoupled in RA, with this phenomenon being tentatively ascribed to abnormal synovial fibroblasts in pannus tissue that are capable of autonomous joint damage. Although this study generally showed a correlation between synovitis and erosion, there was evidence that these processes were divergent, if not uncoupled, at certain sites. However, such differences were related to the position of the joint collateral ligaments in terms of propensity for bone damage. In particular, the predilection for erosion on the radial side was very strong in the third MCP joints whereas the difference in synovial volume between the radial and dorsal side of the same joint was negligible.

    While this study generally showed a direct correlation between the severity of regional synovitis and adjacent erosion, this association was not evident for the fifth MCP joint. At that site, erosions were fairly evenly distributed between the radial and ulnar aspects of the joint but synovitis was more pronounced adjacent to the radial collateral ligament. Anatomic factors may explain this. The ulnar side of the fifth MCP joint is the only one that is not protected by an adjacent MCP joint. Furthermore, the volume of synovitis was greater in the fourth MCP compared with the fifth MCP joint but the latter joint had more erosions, suggesting that the fourth MCP joint may be protected by its anatomic location.

    It therefore seems likely that the mechanisms of erosion are complex and could be affected by the direct effects of the collateral ligaments on the bone in addition to the effects of regional synovitis within joints. This assertion is supported by the finding of a predilection for bone damage on the radial aspect of the second and third MCP joints in normal subjects. These observations suggest that MCP joint inflammation in RA exaggerates the inherent tendency for joint damage adjacent to the radial collateral ligaments.

    In conclusion, the predominance of both synovitis and bone damage on the radial side of the MCP joints suggests that local anatomic and biomechanical factors may be important in the pathogenesis of both synovitis and bone erosion in early RA. Therefore, the existing immunologically based models for joint damage may have to be modified. The findings of this study have important implications in the study of the pathogenic mechanics of joint damage in RA.

    tissue of patients with rheumatoid arthritis. Ann Rheum Dis 2002; 61: 488-92. Links
    38 Kirwan J, Byron M, Watt I. The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand x-rays of patients with rheumatoid arthritis. Rheumatol 2001; 40: 297-301. Links
    39 Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996; 35: 1263-8. Links

  12. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1798116/?tool=pubmed

    Joint replacement surgery is eventually required (within 22 years of onset) in 25% of rheumatoid patients.23 Wolfe et al found a series of variables reflecting disease activity were predictive of total joint arthroplasty and these included the ESR, global severity, and HAQ score. We examined surgical outcome in our cohort at eight years and found that 12 of 39 patients (31%) had had some form of rheumatoid arthritis related orthopaedic surgery, including 10 (26%) who had had joint replacement or arthrodesis. We consider our cohort to represent the spectrum of patients with more severe disease as they were enrolled on the basis of fulfilling ACR criteria for rheumatoid arthritis at presentation, when symptoms had been present for a median of four months. In very early rheumatoid arthritis, these criteria are known to be relatively insensitive and to select for a more severe disease population.24 We found no evidence that MRI variables reflecting the extent of joint erosion and inflammation in early disease could predict surgery at the eight year point. Unfortunately, it is difficult to interpret this result as the small size of our cohort would preclude detection of anything less than a very major effect. Furthermore, the eight year point is relatively early in terms of joint replacement surgery, and studying the same cohort at 15 and 20 years might be necessary to obtain a true picture of this outcome measure. However, there was clear evidence that those in the surgical group had faster progression of MRI erosive change from baseline to one year, indicating that they were destined for more severe articular damage in the long term.Conclusions
    We have presented data suggesting that MRI bone oedema, bone erosion, and to a lesser extent synovitis and tendonitis detected at the wrist in early rheumatoid arthritis have prognostic significance in terms of hand and specifically tendon function in the medium term. Studies conducted over longer periods including larger numbers of patients are required to determine whether early MRI can help to predict surgical outcome.
    23. Wolfe F, Zwillich S H. The long‐term outcomes of rheumatoid arthritis: a 23‐year prospective, longitudinal study of total joint replacement and its predictors in 1600 patients with rheumatoid arthritis. Arthritis Rheum 1998. 411072–1082. [PubMed]

  13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714150/?report=abstract
    The PPV (positive predictive value) of MRI erosions to predict subsequent radiographic erosions was low. Similarly, the PPV of bone marrow edema to predict a later MRI erosion was low. Alternatively, the NPV (negative predictive value) of the absence of an MRI erosion or bone marrow edema predicts that a later radiographic erosion or MRI erosion will likely not develop. Anti-TNF therapies may have resulted in the lower-than-anticipated PPVs. MRI descriptions of bone edema may represent a more critical time to treat in order to avoid damage, whereas an MRI erosion represents more permanent damage. This study suggests that imaging modalities more sensitive than radiographs are necessary to monitor disease in the biologic era

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