| Background and purposeCrohn’s disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Its treatment mainly has 5-aminosalicylic acid (5 ASA), glucocorticoid and immunosuppressants (azathioprine, mercaptopurine, methotrexate), biological agents (tumor necrosis factor antagonists).Along with the development and production of the new TNF drugs, endoscopic technology progress and the deepening of the understanding of crohn’s disease, crohn’s disease treatment goals also gradually change, from clinical remission and mucosal healing to deep remission and histological remission. Recently, in CD the term deep remission has been applied to patients on immunomodulators or TNF-ablocking therapy or both who have no clinical symptoms and no objective signs of inflammation (defined as Crohn’s disease activity index [CDAI<150] and endoscopic remission). Foreign studies have confirmed that CD patients with infliximab(IFX) could achieve deep remission and also maintain deep remission.However, at present, our country is short of reports and a large number of related clinical datas about the function and significance of achieving and maintaining deep remission in CD patients who receive IFX monotherapy or azathioprine (AZA) combination therapy. At the same time,it is also not clear whether "top-down" and "step-up" strategies in CD patients chould affect the efficacy of achieving and maintaining deep remission.Based on the above research background, in this study,a retrospective analysis was performed.And the demographic features,clinical charcteristics,endoscopic features,management and outcomes of 82 patients with CD who receive IFX monotherapy or azathioprine (AZA) combination therapy at NanFang Hospital, Southern Medical University,between May 2011 to May 2015,were analyzed.Our study aimed to compare the efficacy of infliximab monotherapy or infliximab combined azathioprine therapy in inducing and maintaining clinical remission,mucosal healing and deep remission for patients with CD.At the same time, the affect of "top-down" or "step-up" strategies in CD patients in achieving and maintaining deep remission would be discussed.Material and methods1.Subjects:82 patients with CD who receive IFX monotherapy or azathioprine (AZA) combination therapy in the Department of Gastroenterology at NanFang Hospital, Southern Medical University,between May 1,2011 to May 30,2015 were reviewed.The diagnosis of CD should be based on clinical evaluation and a combination of endoscopic,histological,radiological,and/or biochemical investigation,according to Chinese Society of Gastroenterology(CSGE),Inflammtory Bowel Disease group "The Consensus on Diagnosis and Management of Inflammtory Bowel Disease(Guangzhou,2012)"2.Methods:According to different therapy,40 CD patients were assigned into IFX group,42 CD patients were assigned into IFX+AZA group. Laboratory index(WBC, ESR, CRP, ALB,HGB),Crohns disease activity index(CDAI), rate of clinical remission, SES-CD, rate of mucosal healing, rate of deep remissiom and side effects at the beginning of therapy, week 14 and week 30 were recorded and analyzed.3.Statistical analysis:Statistical analysis was performed with SSPSS20.0 software by a medical statistician.Descriptive ststistics of normal distribution were calculated with mean and standard deviations.The emumeration data were calculated with sample number and percentage and compared with Chi-square test, the comparison of before and after treatment in the group were calculated with t-test. Descriptive ststistics of abnormal distribution were calculated with interquartile rang, the comparison of before and after treatment in the group were calculated with Wilcoxon nonparametric test. Aassociation significant is considered when P<0.05.Results1.Outcome of groupingA total of 82 patients were confirmed CD and accept IFX treatment in the Department of Gastroenterology at NanFang Hospital, Southern Medical University,between May 1,2011 to May 30,2015.Among 82 patients,54 were male and 28 were female.The age of diagnosis were from 12 to 57 years,the mean age of diagnosis were (26.0±10.5)years.And there were 79 cases of moderate crohn’s disease,3 cases of severe crohn’s disease.According to the different treatment, patients were divided into IFX and IFX+AZA group,48.8%(40/82) for IFX group, 51.2%(42/82) for IFX+AZA group.2.Basic demographic features of the two goupsIn the IFX group(n=40),there were 28 cases of male,12 cases of women, the mean age for diagnosis was (27.3+9.5)years and the mean age of receiving IFX treatment was (28.0±9.6)years, the mean BMI was (18.5±3.1)kg/m2.22.5%(9/40) of patients had a CD related intestinal surgery before receiving IFX treatment,15.0% (6/40) of patients has extra-intestinal manifestations, including 2 cases of oral ulcer and 4 cases of arthropathy.In the IFX+AZA group(n=42),there were 26 cases of male,16 cases of women, the mean age for diagnosis was (24.8±11.2)years and the mean age of receiving IFX treatment was (25.4±11.3)years, the mean BMI was(17.5±2.7)kg/m2.19.0%(8/42) of patients had a CD related intestinal surgery before receiving IFX treatment, 19.0%(8/42) of patients has extra-intestinal manifestations, including 1 case of arthropathy and nodular erythema,1 case of arthropathy and bilateral eye scleritis,3 cases of oral ulcer,3 cases of arthropathy. The patients’age, gender, parenteral performance data comparison difference of the two groups has no statistical significance (P> 0.05), comparable.3.Laboratory indexes and Body Mass Index (BMI)At week14 and week 30, the patient’s WBC levels, CRP levels, and ESR level of IFX and IFX+AZA group were both decreased significantly,the inflammation under control;BMI,HGB and ALB levels of two groups of patients were increased, the patients nutritional status have been improved obviously. But the laboratory index and BMI level of the two groups has no significant statistical difference.4. Clinical remissionAt weekl4,the CDAI of IFX group decreased significantly[254.0(231.2,268.0] vs.[87.5(55.5,118.0)],P<0.05; the CDAI of IFX+AZA group also decreased significantly [256.0(231.7,346.7)] vs.[85.0(49.8,121.0)],P<0.05;But there was no significant statistical difference between the two groups.The rate of clinical remission of the two group was 90.0%(36/40) vs.83.3%(35/42), P>0.05, there was no significant statistical difference, but the of rate of clinical remission of IFX group was higher.At week30,the CDAI of IFX group decreased significantly [254.0(231.2,268.0)] vs.[75.0(32.9,101.8)],P<0.05; the CDAI of IFX+AZA group also decreased significantly[256.0(231.7,346.7)] vs.[79.6(51.5,142.4)],P<0.05;But there was no significant statistical difference between the two groups.The rate of clinical remission of the two group was 92.5%(37/40)vs.83.3%(35/42), P>0.05, there was no significant statistical difference, but the of rate of clinical remission of IFX group is higher.5.Mucosal healingAt week 14, there were 22 patients received endoscopy in the IFX group and the SES-CD decreased significantly[10.9(7.1,17.1)] vs.[3.6(0,5.3)],P<0.05.In the IFX+AZA group,there were 33 patients received endoscopy and the SES-CD decreased significantly [12.0(6.8,15.2)] vs.[2.8(0,6.6)],P<0.05.The rate of mucosal healing of the two group was 40.9%(9/22) vs.48.5%(16/33), P>0.05, the difference has no statistically significant, but the data show that the rate of mucosal healing of IFX+AZA group is higher.At week30, all patients received endoscopy. In the IFX group,the SES-CD decreased significantly [7.9(5.7,11.6)] vs.[0.6(0,5.5)],P<0.05.In the IFX+AZA group,there were 33 patients received endoscopy and the SES-CD decreased significantly [11.0(6.5,15.0)] vs.[0.1 (0,5.3)],P<0.05.The rate of mucosal healing of the two group was 60.0%(24/40)vs.64.3%(27/42)), P>0.05, the difference has no statistically significant, but the data show that the rate of mucosal healing of IFX+AZA group is higher.6. Deep remission6.1 The rate of deep remissionAt weekl4, there were 22 patients received endoscopy in the IFX group and 33 patients received endoscopy in the IFX+AZA group.The rate of deep remission of the two groups is 36.4%(8/22) vs.45.5%(15/33),P>0.05.At week30,all patients were receive endoscopy, rate of deep remission of the two groups is 57.5%(23/40) vs.59.5%(25/42),P>0.05.The difference has no statistically significant, but the data show that the rate of mucosal healing of IFX+AZA group is higher.At week 14 and week30, patients achieved deep remission has more cases of patients with CRP level<5mg/L in each group.However, there was no statistically significant difference between the two group patients.6.2 Effect of achieving deep remission at week14According to the treatment effect of weekl4,patients in each group were divided into group of achieving deep remission early and group of no deep remmission early.At week30, in IFX group,87.5%(7/8) of patients who achieved deep remission at week14 was maintaining deep remission.In IFX+AZA group,93.3%(14/15) of patients who achieved deep remission at week14 was maintaining deep remission.At week30,the CDAI, SES-CD, the WBC level, ESR level and CRP levels of patients who achieved deep remission at week14 were lower than those who did not achieved deep remission at weekl4.The HGB level, ALB level and BMI of patients who achieved deep remission at week 14 were higher than those who did not achieved deep remission at week14. Achieved deep remission early may be good for controlling inflammation and improving patients’nutritinal status.6.3 Effect of "top-down" and"step-up" strategiesIn the IFX group,27.5%(11/40) patients were treat with "step-up"strategies.In the IFX+AZA group,28.6%(12/42) patients were treat with "step-up"strategies.At week14 and week30,the rate of deep remission of patients who received "step-up"strategies or "top-down"strategies were [33.3%(2/6) vs.37.5%(6/16), P>0.05]and[54.5%(6/11) vs.58.6%(17/29),P>0.05].At week14, in the IFX+AZA group,patients who received "step-up"strategies all failed to achieve deep remission.At week30, in the IFX+AZA group, the rate of deep remission of patients who received "step-up"strategies or "top-down"strategies were 41.7%(5/12) vs.66.7%(20/30),P>0.05.The difference has no statistically significant, but the data show that the rate of deep remission of patients who received "top-down"strategies was higher than those who received"top-down"strategies in both IFX and IFX+AZA group.7. Side effectsThe rate of side sffects of IFX group and IFX+AZA group were25.0%(10/40) vs. 26.2%(11/42),P>0.05, It has no statistical significance.No other serious side sffects occurred in both groups.Conclusionin this retrospective study,we found that both IFX and IFX+AZA therapy could effectively induce and maintain clinical remission,mucosal healing and deep remission in patients with CD.There has no statistically significant difference between the two group.But the data show that the rate of mucosal healing and deep remission of IFX+AZA group were higher than IFX group, the combination therapy may have a better trend to inducing and maintaining mucosal healing and deep remission in patients with CD.And achieve deep remission at early time may help to control inflammation and improve patients’ nutrition level. This study found that"top-down"strategies may help patients achieve deep remission. |
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