Invited Editorials understanding this mechanistic relationship with disease activity. For instance, investigation of novel therapeutic approaches could bypass UV trials, with their potential health risks,6 and more efficiently focus on trials based on more direct mechanisms. At the moment, it is unclear whether the effect of UV light on disease activity is independent of or dependent on vitamin D. If independent, then a new direction of UV-related research can emerge. If dependent, then UV research in IBD will continue to forge ahead in the context of vitamin D. In either case, an individual-level study of UV exposure and IBD activity, as well as clarification of causal mechanisms including vitamin D levels, can be done in parallel and is beneficial to the advancement of this burgeoning area of research.
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2
Editorial: escalation to weekly dosing in adalimumab-treated patients with active ulcerative colitis M. G. Ward & M. P. Sparrow Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia. E-mail: [email protected] doi:10.1111/apt.12896
We read with interest the article by Wolf et al,1 a post hoc analysis of ULTRA 22 demonstrating escalation to weekly (EW) adalimumab (ADA) improves clinical outcomes at 1 year in patients with ulcerative colitis (UC), who have lost response or failed to respond to treatment after week 8. Biological optimisation should be encouraged before switching therapy, however limitations of this analysis arising from the trial design of ULTRA 2 and inherent to all post hoc analyses mean that these results should be interpreted with caution. It is interesting that week 8, (not week 12) was selected to dichotomise participants according to response status, whereas treatment escalation could only occur after week 12. Given that a proportion of patients may require longer to respond to ADA,3 perhaps a week
730
REFERENCES 1. Card TR. Editorial: UV exposure and IBD: should more be done to demonstrate an association before trying to find its mechanism? Aliment Pharmacol Ther 2014; 40: 728–9. 2. Limketkai BN, Bayless TM, Brant SR, Hutfless SM. Lower regional and temporal ultraviolet exposure is associated with increased rates and severity of inflammatory bowel disease hospitalisation. Aliment Pharmacol Ther 2014; 40: 508–17. 3. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 2003; 17: 2386–92. 4. Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 2000; 130: 2648–52. 5. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 2008; 324: 23–33. 6. Lin SW, Wheeler DC, Park Y, et al. Prospective study of ultraviolet radiation exposure and risk of cancer in the United States. Int J Cancer 2012; 131: E1015–23.
12 stratification cut-off may have been more appropriate. Other aspects require consideration. Median time to dose escalation among nonresponders was 288 days, meaning most patients were on EW therapy for
ACKNOWLEDGEMENT The authors’ declarations of personal and financial interests are unchanged from those in the original article.2
Editorial: escalation to weekly dosing in adalimumab-treated patients with active ulcerative colitis M. G. Ward & M. P. Sparrow Department of Gastroenterology, Alfred Hospital, Melbourne, Vic., Australia. E-mail: [email protected] doi:10.1111/apt.12896
We read with interest the article by Wolf et al,1 a post hoc analysis of ULTRA 22 demonstrating escalation to weekly (EW) adalimumab (ADA) improves clinical outcomes at 1 year in patients with ulcerative colitis (UC), who have lost response or failed to respond to treatment after week 8. Biological optimisation should be encouraged before switching therapy, however limitations of this analysis arising from the trial design of ULTRA 2 and inherent to all post hoc analyses mean that these results should be interpreted with caution. It is interesting that week 8, (not week 12) was selected to dichotomise participants according to response status, whereas treatment escalation could only occur after week 12. Given that a proportion of patients may require longer to respond to ADA,3 perhaps a week
730
REFERENCES 1. Card TR. Editorial: UV exposure and IBD: should more be done to demonstrate an association before trying to find its mechanism? Aliment Pharmacol Ther 2014; 40: 728–9. 2. Limketkai BN, Bayless TM, Brant SR, Hutfless SM. Lower regional and temporal ultraviolet exposure is associated with increased rates and severity of inflammatory bowel disease hospitalisation. Aliment Pharmacol Ther 2014; 40: 508–17. 3. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 2003; 17: 2386–92. 4. Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 2000; 130: 2648–52. 5. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 2008; 324: 23–33. 6. Lin SW, Wheeler DC, Park Y, et al. Prospective study of ultraviolet radiation exposure and risk of cancer in the United States. Int J Cancer 2012; 131: E1015–23.
12 stratification cut-off may have been more appropriate. Other aspects require consideration. Median time to dose escalation among nonresponders was 288 days, meaning most patients were on EW therapy for
