Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease

[DustyKat]

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

Abstract:

Background:
Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors.

Aim:
To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse.

Methods:
This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively.

Results:
237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4–8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035).

Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007).

Conclusion:
Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Full Article:

http://onlinelibrary.wiley.com/doi/10.1111/apt.12980/full

 

[FrozenGirl]

Interesting. I though the relapse rate would be higher. I would be interesting to find if the original presenting severity had an relation to the relapse rate.

 

[Catherine]

This a personal opinion only but I think as the use of Faecal Calprotectin becomes more widespread for monitoring disease levels.

More people will be able to attempt a withdrawn as a rising faecal calprotection will hopefully show disease active for clinical symptoms appear.

 

[Lady Organic]

4 years ago, I relapsed about a year after stopping a 6 year thiopurine intake. disease came back with vengeance with mild chronic arthritis.

My friend's husband has a similar Inderterminate colitis just like me, well even more severe since he's been hospitalized twice, and me never, He was thereafter 2 years in remission on thiopurine, he then decided to stop the meds, and is now in complete remission for about 5 years, completly meds free. Some are lucky...

 

[InkyStinky]

Thanks DustyKat! So interesting! Glad studies like this are being done. I'll have to read the whole thing later - hopefully it's ongoing... I'd be really interested in what happens to the stats past a year.

My Crohn's was dx as a kid and was severe. About ten years ago I went off of 6-MP (had been on it for more than 6 years prior), and had a 3 yr med free remission. Then a flare with a new EIM - blood clots.

Glad for the spreading recognition in the GI world on the need for evaluating remission!

Lady Organic - do you know if your friend's husband is being monitored by a GI? I'm not sure length of med-free remission has any bearing on likelihood of future flaring/severity.

 

[Lady Organic]

hi InkyStinky,

my friend's husband has a annual colonoscopy. He also has a new GI now who mentionned last time :'' Are you sure you already had Crohn's? '' !!!

 

[Karma]

I want to come off Aza this year so this paper is pretty interesting to me.

Hopefully my GI will agree to my doing FC before stopping and regular FC while I'm off. That's what I'll be suggesting anyway

 

[JMC]

My own personal story. I took azathioprine for 5 years between 2005 and 2010. In 2010, I decided to stop taking azathioprine due to the inherent long term risks. Almost exactly one year later in July 2011 I had a terrible flare up which caused a temporary obstruction which subsequently led to me having a right hemi-colectomy. Following surgery, I resumed taking azathioprine and as of today, I am still in relatively good health, though obviously still concerned about the long term implications.

What I think is interesting, is the elapsed time between stopping taking azathioprine and CD becoming active again. If, you believe that MAP is the cause of Crohn's (and my resection samples tested positive) and that azathioprine is in fact able to modify your immune response to MAP, you would expect a substantial time lapse between stopping taking the drug and the return of symptoms due to the fact that MAP is a very slow growing bacteria. These results would appear to be consistent with that hypothesis.

 

[Karma]

JMC: I agree with that. I'm hoping that by following the advice in that vetinary paper such as avoiding ground beef and pork as well as only drinking UHT milk and using an antibacterial water filter, I can keep the MAP load low. By using faecal Calprotectin tests regularly I'm hoping to spot reccurance long before any stricturing or penetrating damage can be done.