Smoking significantly increases the risk of developing and worsens Crohn’s disease (CD), yet protects against the development and reduces the severity of ulcerative colitis. It is less clear whether smoking impacts the efficacy of therapeutics in inflammatory bowel disease (IBD). We review the literature regarding the relationship between smoking and the efficacy of medical and surgical therapy in IBD. Smoking is associated with alterations in thiopurine metabolism and may affect time to disease relapse. The outcomes of anti-tumor necrosis factor therapy in active smokers appear neutral with data lacking for newer biologics. Smoking increases the risk of postoperative recurrence in those requiring resection for CD, likely attributable to perturbations of the gut microbiota although further implications of these for disease onset/progression and treatment efficacy remain unclear. Multiple lifestyle and psychosocial confounders are likely under-recognized cofactors in the association between smoking and IBD. Despite the widely promulgated risks associated with cigarette smoking in CD, more incisive data are required to further elucidate the actual relationship between smoking and disease pathways, while accounting for the several negative cofactors prevalent in smokers which cast uncertainty on the magnitude of the direct effect of smoking on disease pathophysiology and the efficacy of therapy.

Smoking significantly increases the risk of developing and worsens Crohn’s disease (CD), yet protects against the development and reduces the severity of ulcerative colitis. It is less clear whether smoking impacts the efficacy of therapeutics in inflammatory bowel disease (IBD). We review the literature regarding the relationship between smoking and the efficacy of medical and surgical therapy in IBD. Smoking is associated with alterations in thiopurine metabolism and may affect time to disease relapse. The outcomes of anti-tumor necrosis factor therapy in active smokers appear neutral with data lacking for newer biologics. Smoking increases the risk of postoperative recurrence in those requiring resection for CD, likely attributable to perturbations of the gut microbiota although further implications of these for disease onset/progression and treatment efficacy remain unclear. Multiple lifestyle and psychosocial confounders are likely under-recognized cofactors in the association between smoking and IBD. Despite the widely promulgated risks associated with cigarette smoking in CD, more incisive data are required to further elucidate the actual relationship between smoking and disease pathways, while accounting for the several negative cofactors prevalent in smokers which cast uncertainty on the magnitude of the direct effect of smoking on disease pathophysiology and the efficacy of therapy.

Carcinoma, Non-Small-Cell Lung ; diagnosis ; metabolism ; China ; Consensus ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; diagnosis ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Polymerase Chain Reaction ; Receptor Protein-Tyrosine Kinases ; metabolism

PURPOSE: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials. MATERIALS AND METHODS: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively. RESULTS: In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity. CONCLUSION: These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.
Asia ; Asian Continental Ancestry Group* ; Carboplatin ; Carcinoma, Non-Small-Cell Lung* ; Cisplatin ; Continental Population Groups ; Diarrhea ; Disease-Free Survival ; Drug Therapy* ; Humans ; Incidence ; Lymphoma ; Nausea ; Pemetrexed ; Phosphotransferases ; Vision Disorders