AIM： To investigate genetic differences between Crohn＇s disease （CD） patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS： Forty-eight ...AIM： To investigate genetic differences between Crohn＇s disease （CD） patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS： Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remis- sion was defined as corticosteroid-free plus normaliza- tion of clinical disease activity [CD activity index （CDAI） 〈 150] during follow-up visits based on physician global assessments. A CD relapse （loss of infliximab-induced remission） was clinically defined as a physician visit for symptoms of disease activity （CDAI 〉 220） and a thera- peutic intervention with CD medication（s）, or a hospital- ization with complications related to active CD. Genetic analyses were performed on samples from 14 patients （n = 6 who had a sustained long term remission after stopping infliximab, n -- 8 who rapidly relapsed after stopping infliximab）. Nucleotide-binding oligomerization domain 2 （NOD2）/caspase activation recruitment do- main 15 （CARD15） polymorphisms （R702W, G908R and L1007fs） and the inflammatory bowel disease 5 （IBDS） polymorphisms （IGR2060a1 and IGR3081a1） were ana- lyzed in each group. RESULTS： Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no signifcant increase in frequency of the NOD2/CARD15 polymor- phisms （R702W, G908R and L1007fs） and the IBD5 polymorphisms （IGR2060al and IGR3081a1） in either group of patients; those whose disease relapsed rap- idly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of re- sponse remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked dif- ference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years 4- 0.6 years, while those still in remission were at the time of this study, 8.1 years 4- 2.6 years post-discon- tinuation of infliximab, P 〈 0.001. The 8 patients who had lost remission after discontinuing infiiximab had a mean number of 5 infusions （range 3-7）, with a mean treatment time of 7.2 mo （range 1.5 mo-15 mo）. The mean duration of time from the last infusion of inflix- imab to the time of loss of remission was 382 d （range 20 d-701 d）. The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions （range 3-12）, with a mean treatment dura- tion of 12 mo （range 3.6 mo-32 too） （P = 0.45 relative to those who lost remission）. CONCLUSION： There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sus- tained remission and which will relapse rapidly after stopping infliximab.展开更多
基金Supported by Center of Excellence for Gastrointestinal,Inflammation and Immunity Research at the University of Alberta
文摘AIM： To investigate genetic differences between Crohn＇s disease （CD） patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-free remission. METHODS： Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remis- sion was defined as corticosteroid-free plus normaliza- tion of clinical disease activity [CD activity index （CDAI） 〈 150] during follow-up visits based on physician global assessments. A CD relapse （loss of infliximab-induced remission） was clinically defined as a physician visit for symptoms of disease activity （CDAI 〉 220） and a thera- peutic intervention with CD medication（s）, or a hospital- ization with complications related to active CD. Genetic analyses were performed on samples from 14 patients （n = 6 who had a sustained long term remission after stopping infliximab, n -- 8 who rapidly relapsed after stopping infliximab）. Nucleotide-binding oligomerization domain 2 （NOD2）/caspase activation recruitment do- main 15 （CARD15） polymorphisms （R702W, G908R and L1007fs） and the inflammatory bowel disease 5 （IBDS） polymorphisms （IGR2060a1 and IGR3081a1） were ana- lyzed in each group. RESULTS： Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no signifcant increase in frequency of the NOD2/CARD15 polymor- phisms （R702W, G908R and L1007fs） and the IBD5 polymorphisms （IGR2060al and IGR3081a1） in either group of patients; those whose disease relapsed rap- idly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of re- sponse remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked dif- ference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years 4- 0.6 years, while those still in remission were at the time of this study, 8.1 years 4- 2.6 years post-discon- tinuation of infliximab, P 〈 0.001. The 8 patients who had lost remission after discontinuing infiiximab had a mean number of 5 infusions （range 3-7）, with a mean treatment time of 7.2 mo （range 1.5 mo-15 mo）. The mean duration of time from the last infusion of inflix- imab to the time of loss of remission was 382 d （range 20 d-701 d）. The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions （range 3-12）, with a mean treatment dura- tion of 12 mo （range 3.6 mo-32 too） （P = 0.45 relative to those who lost remission）. CONCLUSION： There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sus- tained remission and which will relapse rapidly after stopping infliximab.
