Sunday, May 19, 2013

Research Update

IBD Research Briefs

Instead of a major update on a single topic, this week I’ll cover a few interesting pieces of research related to IBD in the past 6 months or so.  The research presented is not comprehensive, nor are the studies individually conclusive (though some may be replications confirming earlier work).  I have tried, however, to choose works that may have an impact in another 12 months on the overall treatment/understanding/etc. of IBD.

Double-dose Humira (adalimumab)

This one has a personal resonance with me – I’m one of the individuals who are on a weekly (as opposed to every other week) dose of Humira, which is an off-label usage.  I moved to this regimen after my Crohn’s stopped responding to the every other week (EOW) injections on the advice of my GI doctor.  Now, there is evidence for a dose-response increase in using weekly Humira injections for those with moderate-to-severe Crohn’s disease and elevated CRP numbers.  In a double-blind study with placebo control, Sandborn et al found that both weekly and EOW Humira doses outperformed placebo in a year-long remission study.  Further, in those with high CRP levels, they found:

[R]emission rate with weekly dosing (46.9%) was statistically significantly greater compared with eow dosing (22.5%)

The results show a lot of promise for weekly dosing in the most severe cases.  The other side of the coin, the safety of doubling the dose, is still an unknown, and would support the use of weekly dosing only in severe cases until further  information on dose-related side effects can be found.  (1)

Humira, Antibiotics, and Fistulae

In a not unexpected result, but confirming what is a common and widespread regimen, a new double-blind study showed that using Cipro in combination with Humira was more effective than Humira alone in closing fistulae.  There are still unanswered questions – does Flagyl work better in combination, or does the trifecta of Humira, Flagyl, and Cipro work better than the others?  Right now, you can’t go wrong with the recommended Humira/Cipro one-two punch, but it will be interesting to see if we can improve even more on this.(2)

Crohn’s, Ulcerative Colitis, and Sleeping

An interesting study by Ananthakrishnan et al looked at both Crohn’s and Ulcerative Colitis in relation to sleep disturbances.  They found that, at enrollment, “Disease activity, depression, female sex, smoking, and use of corticosteroids or narcotics” were associated with increased sleep disturbance.  Interestingly, they found that sleep disturbances to be predictive of an increased risk of flares in Crohn’s disease (2x as likely) but not in Ulcerative Colitis (1.1x as likely).  This is an unusual look at IBD, but may be supportive of good sleep management practices (if causal) or monitoring of sleep practices for prediction of flares (if only correlated).(3)

Could Crohn’s Disease be Multiple Diseases?

The idea that Crohn’s isn’t a single disease, but a variety of diseases that are closely related isn’t new.  This study adds another drop in the bucket toward this hypothesis.  Specifically, a study of the genes present in the submucosal layers in patients showed that Mycobacterium were present in approximately 50% of patients, and 43% of patients showed the presences of genes from an unrelated bacteria family.  The most interesting aspect of the study was the exclusivity – there was no overlap between the two families of genes in the same patient.  The study was small, but could be very important if the results hold up in larger studies, potentially resulting in better targeted treatments.(4)

Bottom Line

Preliminary Research Shows:
·         Weekly use of Humira vice every-other-week is more effective in treating severe Crohn’s
·         Use of an antibiotic with a TNF-alpha drug closes fistulae better than monotreatments
·         Sleep disturbances are related to increased Crohn’s activity, but not increased UC activity
·         A small study on the sub mucosal layers in Crohn’s patients showed two distinct and non-overlapping bacterial profiles

1.       Sandborn, W. J., J. F. Colombel, G. D'Haens, S. E. Plevy, J. Panés, A. M. Robinson, P. F. Pollack, Q. Zhou, M. Castillo, and R. B. Thakkar. "Association of Baseline C-Reactive Protein and Prior Anti-TNF Therapy with Need for Weekly Dosing During Maintenance Therapy with Adalimumab in Patients with Moderate to Severe Crohn's Disease." Current Medical Research & Opinion 0 (2013): 1-34.
2.       Dewint, Pieter, Bettina E. Hansen, Elke Verhey, Bas Oldenburg, Daniel W. Hommes, Marieke Pierik, Cyriel IJ Ponsioen et al. "Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI)." Gut (2013).
3.       Ananthakrishnan, Ashwin N., Millie D. Long, Christopher F. Martin, Robert S. Sandler, and Michael D. Kappelman. "Sleep Disturbance and Risk of Active Disease in Patients with Crohn's Disease and Ulcerative Colitis." Clinical Gastroenterology and Hepatology (2013).
4.       Chiodini, Rodrick J., Scot E. Dowd, Brian Davis, Susan Galandiuk, William M. Chamberlin, John Todd Kuenstner, Richard W. McCallum, and Jun Zhang. "Crohn's Disease May Be Differentiated Into 2 Distinct Biotypes Based on the Detection of Bacterial Genomic Sequences and Virulence Genes Within Submucosal Tissues." Journal of clinical gastroenterology (2013).

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