Kickas.org Forums Ankylosing Spondylitis General Discussion Highlights in Spondylitis Research Are NSAIDS (also) DMARDS (Rbt Inman...et al)

Ann Rheum Dis 2012;71:1593-1595 doi:10.1136/annrheumdis-2012-201844
Editorial
NSAIDs and radiographic progression in ankylosing spondylitis Bagging big game with small arms?
Nigil Haroon1, Tae-Hwan Kim2, Robert D Inman1

http://ard.bmj.com/content/71/10/1593.full

Are NSAIDs disease-modifying antirheumatic drugs (DMARDS)?

(snipped...to end)

"What are the risks of continuous NSAID treatment in this patient? Traditionally, concerns about safety of NSAIDs have related primarily to gastrointestinal or cardiovascular adverse events. Recent studies in AS have heightened concerns in both these areas. The recognition that the same polymorphisms in the interleukin (IL)-23 receptor confer susceptibility to AS and inflammatory bowel disease has led to further investigation of the role of occult bowel inflammation in AS. In the studies of Ciccia et al,32 it was found that the upregulation of IL-23 seen in gut tissues of patients with Crohn's disease is also seen in patients with AS with no gastrointestinal symptoms. This follows the earlier pioneering studies of Mielants and Veys demonstrating that subclinical gut inflammation is a common occurrence in AS. With respect to cardiovascular disease, there is increasing recognition that cardiovascular events occur with increased frequency in AS,33 which may be related to disease activity.34 In the context of inflammatory joint disease, NSAIDs may not confer an increased risk of cardiovascular mortality, but this area needs further study in large cohorts with long-term follow-up.35 In psoriatic arthritis, concerns about cardiovascular and gastrointestinal risks have led to a conservative approach to the use of NSAIDs, with the recommendation being the lowest dose and the shortest treatment duration possible with NSAIDs, in view of their potential toxicity.36

What treatment alternatives are available for this patient? Using the ASAS-EULAR guidelines, the NSAID-unresponsive or NSAID-intolerant patient is on the threshold of biological therapy. One of the central ironies of AS management is that the anti-TNF agents have proved effective for improvement of symptoms of AS, but have not been shown to retard radiographic progression in the disease. The fact that these agents predictably normalise the ESR in AS highlights the complexities, as the current studies on NSAID effect identify elevated ESR as a robust predictor of progression. From the patient's perspective, it is symptomatic improvement in the pain, stiffness and fatigue of the disease that are the primary concerns. And these correlate poorly with mSASSS. But symptomatic status (as reflected by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) turns out to be a poor predictor of the NSAID ‘protective’ effect with respect to radiographic progression. Similarly, there are few studies to inform the decision on whether NSAIDs should be continued when a biological agent is administered, although our recent experience provides supportive evidence for this approach.4 Both for the pivotal phase 3 random control trials of biological agents in AS and current third-party coverage, inadequate control of symptoms by NSAIDs has become the criteria for use of anti-TNF agents. Thus the published literature on the effects of anti-TNF agents on bone formation is based largely on experience with NSAID non-responders.

In the final analysis, treatment of AS must be customised to the individual patient, as set out as the first principle of the ASAS-EULAR Recommendations.1"

Footnotes
Competing interests None.

Provenance and peer review Commissioned; externally peer reviewed



Good paper, very interesting. Glad to see he has emphasised the problem of gut vis-a-vis NSAIDs and plus cardiovascular + re Celecoxibs. Need more of the likes of Inman...seriously *excellent rheumatologist.

Following on from ABOVE research :
http://ard.bmj.com/content/71/10/1616.full

Ann Rheum Dis 2012;71:1616-1622 doi:10.1136/annrheumdis-2011-201252
Clinical and epidemiological research
Extended report
Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort

Competing interests None.

Ethics approval Approval provided by the Central Ethics Committee (Berlin) und local committees of the involved centres.

Provenance and peer review Not commissioned; externally peer reviewed



Worth skimming through -

http://ard.bmj.com/content/71/10/1623.abstract?etoc

Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis

(snip...) "This study definitely has its limitations. Although the analyses were hypothesis-driven, they have the disadvantage of post hoc analyses, and the results need to be confirmed. Confirmatory data from the GESPIC-cohort are recently published, but further studies are needed in other prospective cohorts to confirm these findings.4 Since we have created several subgroups, numbers in some groups were sometimes low. Also, the results shown in the probability plots did not always match with the differences in radiological progression in the diverse subgroups that were found to be significant." (more...)

(snipped to end...) "In conclusion, patients with elevated acute phase reactants seem to benefit most from continuous treatment with NSAIDs. The application of continuous therapy with NSAIDs in patients with elevated acute phase reactants may lead to an improved benefit to risk ratio of these drugs, although it remains important to weigh the risk and benefit in individual patients."

Footnotes
Competing interests None.

Provenance and peer review Not commissioned; externally peer reviewed.



Weak paper (bit of a pot boiler). Does not compare, come near, to Inman's paper.

Really appreciate that you posted these articles here, Molly - thanks!! I had not read about the study by the researchers in Germany yet.

From the first link:
"Interestingly, this protective effect was nearly exclusively seen in patients with elevated C-reactive protein levels over time and the presence of syndesmophytes at baseline."

That is interesting!

First paper, Rbt Inman, was excellent. Sound approach. The German paper is worth skimming through. The French one...don't bother.

Glad you found of interest mig. Thank you for your note -

Take care -

Some interesting info. The first article seems to state many people have a non-progressive form of the disease. It states that ESR and imaging evidence are better predictors of progression than pain, stiffness, and fatigue, except in cases where biologics are used to lower ESR. It says continued NSAID use slows progression in cases where CRP is elevated. What is there for those without elevated CRP or ESR?

Professionals say NSAIDs are good for us and experienced sufferers here tell me NSAIDs are dangerous. I've always avoided them for that reason. So many mixed messages between what these professional studies tell us and the experiences of people on this site. I guess it comes down to whether we trust how we feel or what the physical evidence (X-rays, MRIs, etc) tell us.

NSAIDs ripped my guts apart. Still cannot understand why they keep stuffing em at us even to those of us who have a proven track record of massive nasty side effects. Moi, for starters. (Having had big-time rheumy try that very tactic only a few months ago - and then I was castigated, even though he 'himself' has many papers to his name re NSAIDs and to be very aware of side effects in the AS patient - who most probably has the comorbidity of gut problems! I dumped him). No. One can't invent it. Most upsetting and stressful state of affairs to have to, to be expected to, put up with.

We are all different, and I think that is or would be Inman's take home message. He is one of the few 'world class' rheumies. Well known for his empathy.

Quote: "I guess it comes down to whether we trust how we feel or what the physical evidence (X-rays, MRIs, etc) tell us."
That's about right. Emphasis 'trust how you feel'. That should be the take home message for the patient. IF one reacts 'badly' (to a course of action) then desist.

Every GOOD doctor should be representing the patient.

I tried to find an nsaid that i could tolerate, because nothing worked better on my SI joint inflammation (or foot inflammation or...) than aleve. But it caused gastritis and edema. So did a number of other nsaids and cox 2 inhibitors. or they just weren't very effective. Ran through just about every class of them. Too bad i couldn't find one.

But too, maybe they wouldn't have been the right drug for me either; i don't know. When the GI doc did a colonoscopy all the way up into my ileum and found inflammation and small crohn's like ulcers, I asked him what else could cause them besides the inflammatory disease itself. He stated nsaids. But this was before my nsaid trial. So for me it was the disease itself. However, if I am prone to that, would nsaids have made it worse? Maybe that's the thing to consider; anyone with the propensity for this inflammation in the ileum (which I read is the case for anyone with a spondyloarthropathy (read it could be used as a diagnostic marker)), maybe that subset of people shouldn't take nsaids? I don't know, but that's what i wonder.

I didn't even know there was a non-progressive form. Can people have AS all their life but remain somewhat stable and never really lose more ROM?

Hi Wilhelm - Yes. Can happen. There are even some persons who go into remission (*rare, but 'can' happen). I seem to have stabilised. Am nothing like as bad as I was even to a year ago. Hoping (!) I continue at this reasonably stable level. But sure is good whilst it is lasting... Wish feet would stop hurting and neck would give over being such a pest and, and - but...

Yes. One can stabilise. 'Smile'.