Effect of smoking on the efficacy of TNF inhibitors in the treatment of chronic inflammatory inmune-mediated diseases: systematic review and meta-analysis

Abstract

Background: Chronic inflammatory immune-mediated diseases, as rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (Ps), ankylosing spondylitis (AS), ulcerative colitis (UC) and Crohn’s disease (CD), have higher risks of morbidity and mortality and a great impact on quality of life of patients1. Drug inhibitors of tumor necrosis factor (TNF inhibitors) have demonstrated an adequate efficacy and security profile in these patients when classical treatments (as disease-modifying antirheumatic drugs) have been failed or patients were intolerant. TNF inhibitors are used to control inflammatory response and to improve quality of life, pain, functional capacity and progression of the disease2. Studies in RA show that smoking habit is related to more articular and extra-articular damage, worse prognosis, higher basal activity and higher risk of seropositive RA. It has been related also to greater number of different treatments and higher doses needed for patients by pharmacokinetic and pharmacodynamic processes. Data published until now suggest that smoking habit decreases efficacy of TNF inhibitors3.

Objectives: To analyze the smoking habit influence on the efficacy of TNF inhibitors in patients diagnosed of chronic inflammatory immune-mediated diseases (RA, PsA, Ps, AS, UC, CD).

Methods: It was made a systematic literature search using Cochrane Library, Medline, the Web of Science and Embase databases. Meta-analyses were performed using a random-effects model.

Results: 37 of 3677 identified articles met the inclusion criteria. No documents with GOL were found. The analysis of all the diseases together gives a significant decrease on the response to TNF inhibitors in smoking patients [OR 0.812 (0.662-0.996), p=0.046]. This response also has a significant decrease in IBD maintained response in smoking patients [OR 0.467 (0.257-0.848), p=0.012]. A non-significant decrease in the treatment response of smoking patients with IBD clinical remission was found, in smoking patients versus ex-smoking and never smoking patients with IBD response, in ex-smoking patients versus never smoking patients with IBD partial response, in current and ex-smoking patients versus never smoking patients with IBD partial response, in current smoking patients versus ex-smoking patients with IBD partial response, in current smoking patients versus never and ex-smoking patients with IBD partial response, in current smoking patients versus never smoking patients with IBD partial response, in patients with AR EULAR and in patients with AR EULAR moderate response.

Conclusion: Smoking habit is a poor prognosis factor in RA, AS, Ps, PsA, UC and CD. Its leaving will decrease cardiovascular risk, joint and bowel damage, will increase the efficacy of TNF inhibitors and will benefit the health of patients, not only in their particular disease, and it can be the first step on their treatment.