Letter: Biologics are effective in neutralising the detrimental effect of smoking on the natural course of Crohn's disease

DEAR SIRS, We read with great interest the systematic review with meta-analysis by To et al.1 regarding the effects of smoking on disease course in Crohn’s disease (CD). The authors analyzed 33 studies comparing CD patients, smokers vs. nonsmokers, and observed that smokers had increased odds of flare of disease activity (OR, 1.56), flare after surgery (OR, 1.97), need for first surgery (OR, 1.68) and need for second surgery (OR, 2.17). Furthermore, the odds of these outcomes among previous smokers diminished after smoking cessation, leading the authors to suggest that smoking should be avoided to reduce disease burden in these patients We appreciated the efforts made by the Authors to clarify the role of smoking which has been shown to play a major detrimental effect on the natural history of CD. However, we would like to underline that some relevant data available in medical literature have not been included. Indeed, recent studies on the prophylactic use of biologics at preventing CD recurrence after resective surgery provided further important information on the role of smoking and the effects of drugs in reducing its impact on the natural course of the disease.2–4 In particular, Regueiro et al.,2 by comparing infliximab (IFX) vs. placebo in a randomised study enrolling 24 patients with CD who had undergone ileocolonic resection, and more recently, Savarino et al.,4 by evaluating in a randomised, three-armed, controlled study the rate of endoscopic and clinical recurrence in three groups of CD operated patients (n = 51) treated with adalimumab (ADA), azathioprine or mesalazine (mesalamine), demonstrated that, despite the presence of cigarette smokers at baseline and throughout the study, the endoscopic and clinical recurrence rates were significantly lower in the anti-TNF groups, using both IFX and ADA, than in the control groups. So far, biologics were found to be effective not only at preventing post-operative disease recurrence with almost a 90% of success but also to relieve the detrimental effect of smoking on disease recurrence and, therefore, on CD natural history. On the other hand, we have to mention a recent systematic review by Ding et al. who found that smoking status has been associated with primary nonresponse and secondary loss of response to anti-TNF therapy, although the examined studies did not include just operated patients with absent disease, but those with ongoing active illness, in whom the natural history of CD had been already influenced by environmental and other factors such as smoking.5 In conclusion, the above data suggest that, although smoking cessation remains of paramount importance in preventing CD recurrence, anti-TNF drugs may effectively counteract the effect of cigarette smoking on postoperative disease relapse, and its major detrimental effect on CD natural history should be re-evaluated by considering that the majority of available data up to date are based on studies carried out with drugs (i.e. thiopurines and mesalazine) that have been shown to be poorly effective in modifying the natural history of CD.