Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. Controlled trial of azathioprine in Crohn's disease. A method for assessing the quality of a randomized control trial. Effect of azathioprine or mesalazine therapy on incidence of re-hospitalization in sub-occlusive ileocecal Crohn’s disease patients Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: a controlled randomized trial. Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study. Infliximab, azathioprine, or combination therapy for Crohn's disease. Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial Treatment of Crohn's disease with 6-mercaptopurine. A long-term, randomized, double-blind study. DOUBLE-BLIND WITHDRAWAL TRIAL OF AZATHIOPRINE AS MAINTENANCE TREATMENT FOR CROHN'S DISEASE Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial. 6‐Mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid‐dependent inflammatory bowel disease Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse. Azathioprine and 6-mercaptopurine have a role in the treatment of Crohn's disease Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn's disease. Methotrexate in chronic active Crohn's disease: a double-blind, randomized, Israeli multicenter trial. Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn's disease: open-label prospective study. Treatment of Crohn's disease with azathioprine: a controlled evaluation. A controlled trial of azathioprine in Crohn's disease Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial Azathioprine Is Superior to Budesonide in Achieving and Maintaining Mucosal Healing and Histologic Remission in Steroid‐Dependent Crohn's Disease Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease. Addition of Metronidazole to Azathioprine for the Prevention of Postoperative Recurrence of Crohn’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine. Controlled trial of azathioprine in Crohn's disease. A Multicenter, Randomized, Double-Blind Trial of Everolimus Versus Azathioprine and Placebo to Maintain Steroid-Induced Remission in Patients With Moderate-to-Severe Active Crohn's Disease Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. [Intention-to-treat].
Objective The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn 's disease ( CD ) with moderate or severe endoscopic recurrence . Methods This was a 1 year , double-blind , double-dummy , r and omised study which took place in 21 gastroenterology centres in Austria , the Czech Republic , Germany and Israel . The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6–24 months without subsequent clinical recurrence and with a Crohn 's disease activity index ( CDAI ) score < 200 , but with moderate or severe endoscopic recurrence . The study drugs were azathioprine 2.0–2.5 mg/kg/day or mesalazine 4 g/day over 1 year . The primary end point was therapeutic failure during 1 year , defined as a CDAI score ≥200 and an increase of ≥60 points from baseline , or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction . Results Treatment failure occurred in 22.0 % ( 9/41 ) of azathioprine-treated patients and 10.8 % ( 4/37 ) of mesalazine-treated patients , a difference of 11.1 % ( 95 % CI −5.0 % to 27.3 % , p=0.19 ) . Clinical recurrence was significantly less frequent with azathioprine versus mesalazine ( 0/41 ( 0 % ) vs 4/37 ( 10.8 % ) , p=0.031 ) , whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients ( 9/41 ( 22.0 % ) vs 0 % , p=0.002 ) . The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3 % ( 19/30 ) and 34.4 % ( 11/32 ) in the azathioprine and mesalazine groups , respectively ( p=0.023 ) . Conclusions In this population of patients with postoperative CD at high risk of clinical recurrence , superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure . Clinical trial registration number NCT00946946 BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients The effect of azathioprine in patients with active Crohn 's disease has been evaluated in a double-blind cross-over trial . Fifteen patients were treated with both azathioprine and placebo : only two improved while on azathioprine , six got worse , and in seven there was no change . The drug seemed to be the cause of deterioration in two of the patients . Although the drug may be of some value in a few patients , it should be used with caution and only when other measures have failed A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background Although the cost of Crohn ’s disease ( CD ) treatment differs considerably , hospitalization and surgery costs account for most of the total treatment cost . Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs . Material / Methods We evaluated the effect of azathioprine ( AZA ) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries . In this controlled , r and omized study , 72 subjects with sub-occlusive ileocecal CD were r and omized for AZA ( 2–3 mg/kg per day ) or mesalazine ( 3.2 g per day ) therapy during a 3-year period . The primary end point was the re-hospitalization proportion due to all causes , as well as for surgical procedures during this period evaluated between the groups . Results On an intention-to-treat basis , the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine ( 0.39 vs. 0.83 , respectively ; p=0.035 ) . The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention ( 0.25 vs. 0.56 , respectively ; p=0.011 ) . The number of admissions ( 0.70 vs. 1.41 , p=0.001 ) and the length of re-hospitalization ( 3.8 vs. 7.7 days ; p=0.002 ) were both lower in AZA patients . Conclusions Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period . The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis . We compared the efficacy of early treatment ( within 6 months after diagnosis ) with azathioprine versus conventional management of patients at high risk for disabling disease . METHODS We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease . From July 2005 to November 2010 , patients at 24 French centers were r and omly assigned to treatment with azathioprine ( 2.5 mg ∙ kg(-1 ) ∙ day(-1 ) , n = 65 ) or conventional management ( azathioprine only in cases of corticosteroid dependency , chronic active disease with frequent flares , poor response to corticosteroids , or development of severe perianal disease ) ( n = 67 ) . The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion . RESULTS During the 3-year follow-up period , 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy . Forty-one patients in the conventional management  group required immunosuppressant therapy  ( 61 % ; median time to first prescription , 11 months ) . In the azathioprine group , a median 67 % of trimesters were spent in remission ( interquartile range , 11%-85 % ) compared with 56 % in the conventional management group ( interquartile range , 29%-73 % ) ( P = .69 ) . Among secondary outcomes , a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group ( 96 % ± 3 % and 82 % ± 6 % at month 36 , respectively ; P = .036 ) . The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups . CONCLUSIONS Based on results from a clinical trial , administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission . Clinical trials.gov , Number NCT00546546 BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Introduction : Azathioprine is effective for maintenance of remission in Crohn 's disease , however , duration of efficacy and the dose response relationship has not been fully evaluated BACKGROUND & AIMS More than 80 % of Crohn 's disease ( CD ) patients undergoing resection suffer recurrence of their disease . Therapy with aminosalicylates , antimetabolites , or antibiotics leads to a modest reduction in the incidence of recurrence . GOAL We sought to examine whether metronidazole for 3 months together with azathioprine ( AZA ) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in " high-risk " patients . METHODS CD patients undergoing curative ileocecal resection with > or=1 risk factor for recurrence received metronidazole ( 3 months ) and AZA/placebo ( 12 months ) . The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery . Secondary end points included clinical recurrence , safety , and tolerability of treatment . RESULTS Eighty-one patients were r and omized ; 19 discontinued the study early .  Significant endoscopic recurrence was observed in 14 of 32 ( 43.7 % ) patients in the AZA group and in 20 of 29 ( 69.0 % ) patients in the placebo group at 12 months postsurgery ( P = .048 ) . Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 ( 55 % ) in the AZA group and 32 of 41 ( 78 % ) in the placebo group at month 12 ( P = .035 ) . At month 12 , 7 of 32 patients had no endoscopic lesions in the AZA group , versus 1 of 29 in the placebo group ( P = .037 ) . CONCLUSIONS Despite the enhanced risk of recurrence , the overall incidence of significant recurrence was rather low , probably owing to the metronidazole treatment that all patients received . Concomitant AZA result ed in lower endoscopic recurrence rates and less severe recurrences 12 months postsurgery , predicting a more favorable clinical outcome . This combined treatment seems to be recommendable to all operated CD patients with an enhanced risk for recurrence BACKGROUND AND AIMS Patients with Crohn 's disease ( CD ) often require surgery over their clinical course . However , endoscopic and clinical recurrence of disease appear respectively in up to 80 % and 30 % of patients after one year . Thus , a prophylactic treatment is needed to reduce the possibility of recurrence . Both azathioprine and infliximab have been demonstrated to be effective , but head to head studies have not been performed so far . Aim of this open-label prospect i ve study was to analyse endoscopic , histological and clinical recurrence after one year of treatment with azathioprine or infliximab as postoperative therapies in CD patients with " high risk " of recurrence . METHODS Consecutive CD patients who underwent curative ileocolonic resection were r and omized ( 1:1 ) to receive infliximab ( st and ard induction and maintenance schedule ) or azathioprine ( 2.5 mg/kg/day ) for 1 year . Co- primary endpoints were endoscopic , histological and clinical recurrence after 12 months of therapy . RESULTS Twenty-two consecutive CD patients ( 15 male ; median age 32 years , IQR 22 - 38 ) were enrolled after curative ileocolonic resection . Eleven patients were treated with infliximab and 11 received azathioprine . Among patients treated with azathioprine , 4/10 ( 40 % ) had endoscopic recurrence compared to 1/11 ( 9 % ) in the infliximab group ( p=0.14 ) . Eight out of 10 ( 80 % ) among those who received azathioprine had severe histological activity , whereas 2/11 ( 18 % ) in the infliximab group presented histological recurrence ( p=0.008 ) . No significant clinical differences were found between the two groups . CONCLUSIONS Infliximab was more effective than azathioprine in reducing histological , but not endoscopic and clinical recurrence after curative ileocolonic resection in " high risk " CD patients BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . OBJECTIVES : Postsurgical recurrence of Crohn 's disease ( CD ) is very frequent and , to date , only infliximab has been shown to be useful in preventing it . The efficacy of adalimumab ( ADA ) is poorly known . We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence . METHODS : We r and omly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery  ADA at the dose of 160/80/40 mg every two weeks , azathioprine ( AZA ) at 2 mg/kg/day , or mesalamine at 3 g/day , and they were followed up for 2 years . The primary end point was the proportion of patients with endoscopic and clinical recurrence . Secondary end point was the assessment of quality of life by means of a previously vali date d question naire . RESULTS : The rate of endoscopic recurrence was significantly lower in ADA ( 6.3 % ) compared with the AZA ( 64.7 % ; odds ratio (OR)=0.036 ( 95 % confidence interval ( CI ) 0.004–0.347 ) ) and mesalamine groups ( 83.3 % ; OR=0.013 ( 95 % CI 0.001–0.143 ) ) . There was a significantly lower proportion of patients in clinical recurrence in the ADA group ( 12.5 % ) compared with the AZA ( 64.7 % ; OR=0.078 ( 95 % CI 0.013–0.464 ) ) and mesalamine groups ( 50 % ; ( OR=0.143 ( 95 % CI 0.025–0.819 ) ) . The quality of life was higher in the ADA ( 202 ) than in the AZA ( 90 ; OR=0.028 ( 95 % CI 0.004–0.196 ) ) and mesalamine groups ( 98 ; OR=0.015 ( 95 % CI 0.002–0.134 ) ) . CONCLUSIONS : The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD . Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implication s of biologic therapy in this field To test the effectiveness of 6-mercaptopurine ( 6-MP ) in the treatment of Crohn 's disease , we entered 83 chronically ill patients into a two-year double-blind study comparing 6-MP with placebo .  Crossover data showed that improvement occurred in 26 of 39 courses of 6-MP ( 67 % ) as compared with three of 39 courses of placebo ( 8 % ) ( P less than 0.001 ) . Non-crossover data likewise confirmed the superiority of 6-MP . The drug was more effective than placebo in closing fistulas ( 31 vs 6 % ) and in permitting discontinuation or reduction of steroid dosage ( 75 vs. 36 % ) ( P less than 0.001 ) . The onset of response to 6-MP was often delayed , with 32 % of patients taking longer than three months to respond , and 19 % taking longer than four months . Adverse side effects to 6-MP occurred in 10 % of patients and were uniformly reversible . We conclude that 6-MP is an effective and useful agent in the management of Crohn 's disease 51 patients with Crohn 's disease who were in good health while taking azathiprine , 2 mg/kg body-weight/day , for at least six months were allocated either to a group in which azathioprine was continued or to one in which a control tablet was substituted . The trial lasted one year unless relapse recurred earlier . The cumulative probability of relapse was nil at six months and 5 % ( + /-5 S.D. ) at a year among those on azathioprine , compared with 25 % ( + /-9 S.D. ) at six months and 41 % ( + /-11 S.D. ) at a year among those in the control group ( P less than 0.01 ) . 1 patient in whom azathioprine was continued died of pancytopenia in the fourth month of the trial . Azathioprine is potentially toxic but appears to reduce the relapse-rate in Crohn 's disease BACKGROUND & AIMS The benefit to risk ratio of concomitant immunosuppressives with scheduled infliximab ( IFX ) maintenance therapy for Crohn 's disease is an issue of debate . We aim ed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label , r and omized , controlled trial . METHODS Patients with controlled disease > or = 6 months after the start of IFX ( 5 mg/kg intravenously ) combined with immunosuppressives were r and omized to continue ( Con ) or to interrupt ( Dis ) immunosuppressives , while all patients received scheduled IFX maintenance therapy for 104 weeks . Primary end point was the proportion of patients who required a decrease in  IFX dosing interval or stopped IFX therapy . Secondary end points included IFX trough levels , safety , and mucosal healing . RESULTS A similar proportion ( 24/40 , 60 % Con ) and ( 22/40 , 55 % Dis ) of patients needed a change in  IFX dosing interval or stopped IFX  therapy ( 11/40 Con , 9/40 Dis ) . C-reactive protein ( CRP ) was higher and IFX trough levels were lower in the Dis group ( Dis : CRP , 2.8 mg/L ; interquartile range [ IQR ] , 1.0 - 8.0 ; Con : CRP , 1.6 mg/L ; IQR , 1.0 - 5.6 , P < .005 ; trough IFX : Dis : 1.65 microg/mL ; IQR , 0.54 - 3.68 ; Con : 2.87 microg/mL ; IQR , 1.35 - 4.72 , P < .0001 ) . Low IFX trough levels correlated with increased CRP and clinical score . Mucosal ulcers were absent at week 104 in 64 % ( Con ) and 61 % ( Dis ) of evaluated patients with ongoing response to IFX . CONCLUSIONS Continuation of immunosuppressives beyond 6 months offers no clear benefit over scheduled IFX monotherapy but is associated with higher median IFX trough and decreased CRP levels . The impact of these observations on long-term outcomes needs to be explored further Background As treatment of steroid‐dependent patients with inflammatory bowel disease ( IBD ) is controversial , we analysed the efficacy and tolerance of 6‐mercaptopurine ( 6‐MP ) and methotrexate ( MTX ) added to prednisone in increasing and maintaining the disease remission rate . Methods Seventy‐two steroid‐dependent IBD patients , 34 with ulcerative colitis ( UC ) and 38 with Crohn 's disease ( CD ) , receiving treatment with prednisone  were r and omly assigned in a 2:2:1 ratio to additionally receive , orally , over a period of 30 weeks 1.5 mg/kg/day of 6‐MP ( group A ) or 15 mg/week of MTX ( group B ) , or 3 g/day of 5‐aminosalicylic acid ( 5‐ASA ) ( group C ) . All patients who achieved remission were included in a maintaining remission study for 76 weeks . Remission was defined after stopping prednisone as a CD activity index of < 150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score < 7 for UC patients . Results With regard to achieved remission , a significantly higher ( P < 0.05 ) rate existed for UC patients in group A ( 78.6 % ) than in group C ( 25 % ) , with no statistical differences in group B ( 58.3 % ) versus C. For CD patients , the rates were significantly higher ( P < 0.001 and 0.01 , respectively ) in groups A ( 93.7 % ) and B ( 80 % ) versus C ( 14 % ) . With regard to maintaining remission , UC patients in group A ( 63.6 % ) presented significantly higher rates ( P < 0.0015 and P < 0.001 , respectively ) versus 14.3 % in group B and none in group C. For CD patients , statistical differences ( P < 0.001 ) existed when comparing rates in groups A ( 53.3 % ) and B ( 66.6 % ) versus none in group C. Noticeable side effects appeared in 13.3 % of patients from group A and 11.5 % from group B. Conclusions These results suggest that 6‐MP or MTX added to prednisone could be effective in steroid sparing , as well as in achieving and maintaining remission in steroid‐dependent IBD patients . MTX was less effective in maintaining remission in UC patients BACKGROUND & AIMS Azathioprine ( AZA ) withdrawal in Crohn 's disease after long-term remission under treatment is controversial . In a Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif r and omized , double-blind , placebo-controlled trial , the hypothesis that AZA withdrawal was not inferior to AZA continuation in patients in prolonged clinical remission could not be shown . METHODS A cohort of 66 patients in prolonged remission while being treated with AZA who stopped AZA , during or at the end of the r and omized controlled trial , underwent long-term follow-up evaluation . The primary end point was clinical relapse . Prognostic factors of relapse were looked for through a proportional hazards model . RESULTS Median duration s of AZA therapy and of clinical remission were 68.4 months ( interquartile range , 52.8 - 85.2 mo ) and 63.6 months ( interquartile range , 48.0 - 55.7 mo ) , respectively . The median follow-up time after AZA interruption was 54.5 months ; 32 of 66 patients had a relapse . The cumulative probabilities + /- SE of relapse at 1 , 3 , and 5 years were 14.0 % + /- 4.3 % , 52.8 % + /- 7.1 % , and 62.7 % + /- 7.2 % , respectively . C-reactive protein concentration of 20 mg/L or greater ( risk , 58.6 ; 95 % confidence interval , 7.5 - 457 ; P = .002 ) , hemoglobin level less than 12 g/dL ( risk , 4.8 ; 95 % confidence interval , 1.7 - 13.7 ; P = .04 ) , and neutrophil count 4 x 10(9)/L or greater ( risk , 3.2 ; 95 % confidence interval , 1.6 - 6.3 ; P = .003 ) were associated independently with an increased risk of relapse . Among the 32 relapsing patients , 23 were retreated by AZA alone , all but 1 up to successful remission . CONCLUSIONS Our results confirm that AZA withdrawal is associated with a high risk of relapse , whatever the duration of remission under this treatment . These data suggest that if AZA is well tolerated , it should not be interrupted In 1979 the report of the National Cooperative Crohn 's Disease Study stated that azathioprine , in a daily dose of 2.5 mg/kg , was not significantly more effective than was placebo in suppressing active Crohn 's disease ( 1 ) . Furthermore , analysis of patients by subgroups failed to identify any category which responded favorably to azathioprine . Finally , there was no evidence that azathioprine was able to maintain a remission better than placebo treatment . These conclusions appeared in conflict with those of several other investigators , including a study carried out by O'Donoghue et al ( 2 ) . Since then , Present et al ( 3 ) have presented data indicating that 6-mercaptopurine , the active metabolite of azathioprine , was effective in the treatment of Crohn 's disease . On the basis of these apparent conflicts the " azathioprine controversy " was conceived . John Lennard-Jones is professor of gastroenterology at the London Hospital Medical College and consultant gastroenterologist at St , Mark 's Hospital , London . Dr. Lennard-Jones argues that azathioprine and 6-mercaptopurine have a role in the treatment of Crohn 's disease . John W. Singleton is associate professor of medicine in the Division of Gastroenterology at the University of Colorado Health Sciences Center in Denver . Dr. Singleton was principal investigator and coordinator in the National Cooperative Crohn 's Disease Study . Dr. Singleton presents the view that  azathioprine  has a very limited role in the treatment of Crohn 's disease . These manuscripts clarify certain discrepancies apparent in the literature and should help dispel existing confusion and controversy . ALLEN L. GINSBERG , BACKGROUND & AIMS The effect of different treatment regimens on antibody responses to infliximab  and their clinical significance was examined by using data from ACCENT I. METHODS Patients with Crohn 's disease ( n = 573 ) received 5 mg/kg infliximab ( week 0 ) and then were r and omly assigned to blinded infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo ( group I ) , 5 mg/kg infliximab ( group II ) , or 5 mg/kg infliximab at weeks 2 and 6 , followed by 10 mg/kg thereafter ( group III ) . At week 14 or later , patients losing response could cross over to episodic infliximab treatment increased by 5 mg/kg . Sample s for antibody determination were collected before the first infusion and at weeks 14 , 22 , 54 , 62 , 72 , and , if applicable , before and after crossover . RESULTS Through week 72 , antibodies to infliximab  were detected in 30 % , 10 % , and 7 % of groups I , II , and III , respectively ( P < 0.0001 ) . Patients receiving immunomodulators had a lower incidence of antibodies compared with patients receiving  infliximab alone ( 10 % and 18 % , respectively ; P = 0.02 ) . Antibodies were associated with a 12 % absolute increase in infusion reactions but no increase in serious infusion reactions or serum sickness-like reactions . In the overall population , similar proportions of antibody-positive and antibody-negative patients achieved clinical response ( 64 % and 62 % , respectively ; P = NS ) or clinical remission ( 41 % and 39 % , respectively ; P = NS ) at week 54 . Notably , 86 % of patients responded to retreatment , and 63 % were in clinical response at week 54 ; however , fewer antibody-positive group I patients attained clinical remission ( 31 % ) compared with those who were antibody negative ( 37 % ) or antibody inconclusive ( 54 % ) ( P = NS ) . CONCLUSIONS Reduced antibody formation and greater clinical benefit were observed with an induction regimen followed by maintenance treatment compared with a single dose followed by episodic retreatment in Crohn 's disease patients treated with infliximab BACKGROUND At present only one large controlled study has indicated that parenteral methotrexate may be effective in chronic active Crohn 's disease ( CD ) . AIM To evaluate the effectiveness of oral methotrexate in chronic steroid-dependent CD . PATIENTS Patients with active CD , who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months and with a current Harvey-Bradshaw index of > or = 7 were studied . METHODS Methotrexate ( 12.5 mg weekly ) or 6-mercaptopurine ( 50 mg daily ) , or placebo were given during the 9 months of the trial in addition to steroids and 5-aminosalicylic acid as clinical ly indicated . RESULTS Eighty-four patients were included ( methotrexate , 26 patients ; 6-mercaptopurine , 32 patients ; placebo , 26 patients ) . The proportion of patients entering first remission as well as the proportions of patients relapsing after first remission were not significantly different between the groups . The mean Harvey-Bradshaw index and the mean monthly steroid dose were also similar . However , when each patient was evaluated as his or her own control , the reduction in steroid dose , the general well being , and the reduction in abdominal pain were significantly better in the methotrexate treated patients . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was found to be moderately better than 6-mercaptopurine and placebo in patients with chronic active CD Objective . Recurrence of Crohn 's disease ( CD ) after surgery is common . Azathioprine/6-mercaptopurine ( Aza/6-MP ) is effective in controlling medically induced remission but , so far , has only been sparsely investigated after surgically induced remission . This study comprises a subset of CD patients considered to have an aggressive disease course and chosen for treatment with Aza postoperatively . Material and methods . In 1989–2000 , a total of 100 patients with CD were given  Aza/6-MP as a postoperative prophylaxis . Fourteen Aza/6-MP-intolerant patients were compared with 28 Aza-tolerant patients , matched for gender , age , and duration of disease . Patients were prospect ively registered for symptoms using a modified Crohn 's disease activity index ( CDAI ) and perceived health was assessed on a visual analogue scale ( VAS ) . The primary outcome variable was the modified CDAI postoperatively integrated over time ; other variables were time to first relapse ( modified CDAI ≥ 150 ) , time to first repeated surgery , number of courses of steroids , and repeated surgery per year of follow-up . Patients were followed for a median of 84.7months ( 23.2–140 ) . Results . The modified CDAI integrated over time was 93 for Aza-treated patients compared with 184 for controls ( p=0.01 ) and time to first relapse was 53 and 24 months , respectively ( p<0.05 ) . Aza-treated patients needed fewer courses of corticosteroids ( p=0.05 ) compared with controls . Perceived health did not differ between the groups , nor did need of repeated surgery . Time to first repeat operation was 53 and 37 months , respectively . Conclusions . In CD patients considered to have an aggressive disease course , Aza reduced symptoms after surgery and prolonged the time to symptomatic relapse . The findings support a role for Aza as a postoperative maintenance treatment in CD BACKGROUND A substantial number of patients with Crohn 's disease ( CD ) become dependent on steroids after induction therapy . Treatment with azathioprine ( AZA ) may be beneficial in such patients . The present open-label study evaluated the long-term safety and efficacy of AZA in steroid-dependent CD patients . METHODS Adult patients with steroid-dependent CD were enrolled for AZA therapy over a 7-year period . The average dose of AZA was 2.0 - 3.0 mg/kg per day , adjusted according to clinical response and occurrence of adverse effects . Steroid therapy was tapered off according to a predefined schedule . Long-term outcome and adverse reactions were evaluated . RESULTS Sixty-nine patients were prospect ively included .  Steroid-free remission was achieved in 68 - 81 % of patients , partial response in 14.5 - 27.3 % and failure to respond to AZA in 4 - 15.9 % over the initial 48 months . However , the rate of wean from steroid therapy decreased to 53 - 60 % while the rate of failure increased from 6.7 % to 17.6 % after this period . A breakthrough of symptoms during continuous AZA therapy was common , particularly after 48 months on AZA . The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non-responders ( 5197 + /- 1250 cells/mm(3 ) vs 8340 + /- 1310 cells/mm(3 ) , respectively ; P < 0.01 ) . Azathioprine was relatively well-tolerated and the incidence of serious adverse effects was small . CONCLUSIONS Azathioprine was relatively safe and moderately effective for long-term maintenance of steroid-free clinical remission in corticosteroid-dependent CD patients . Patients were more successfully weaned from prednisone treatment , and clinical remission was more often maintained during the first 48 months of AZA therapy . A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence To determine whether azathioprine is an effective drug in the treatment of Crohn 's disease a double-blind study was performed . Twenty-seven patients with involvement of either small or large intestine or both were r and omized to either a treatment group ( azathioprine 3 mg per kg of body weight ) or a placebo group for 4 months . During the subsequent 4-month period , the treatment schedule of the two groups was reversed . Although some patients improved dramatically on azathioprine , others improved during the placebo period . This study does not provide evidence to support the effectiveness of  azathioprine  in the treatment of Crohn 's disease To determine the efficacy of azathioprine in the treatment of Crohn 's disease , a 26-week double-blind trial was performed . 20 patients with Crohn 's disease , requiring at least 10 mg of prednisone/day over the 3 months prior to entering the study were r and omized into placebo ( 10 patients ) and azathioprine ( 10 patients ) treatment groups . Reduction of steroids was the major criterion of success in the trial . There were 7 relapses in the placebo group ( 5 patients ) and 2 relapses in the azathioprine group ( 2 patients ) . Complications including fistulae were not affected by the medications . The mean reduction in steroid dosage in the azathioprine group at the end of the trial ( −15.5 mg ) was greater than in the placebo group ( −6.1 mg ) . These results suggest that azathioprine may permit reduction or discontinuation of steroids without the worsening of symptoms in some patients who appear to require steroids for control of their symptoms . The clinical features of this “ AZA-responsive subgroup ” remain to be defined BACKGROUND Most patients who have active Crohn 's disease are treated initially with corticosteroids . Although this approach usually controls symptoms , many patients become resistant to or dependent on corticosteroids , and long exposure is associated with an increased risk of mortality . We aim ed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn 's disease who had not previously received glucocorticoids , antimetabolites , or infliximab .  METHODS We did a 2-year open-label r and omised trial at 18 centres in Belgium , Holl and , and Germany between May , 2001 , and January , 2004 . We r and omly assigned 133 patients to either early combined immunosuppression or conventional treatment .  The 67 patients assigned to combined immunosuppression received three infusions of infliximab ( 5 mg/kg of bodyweight ) at weeks 0 , 2 , and 6 , with azathioprine . We gave additional treatment with infliximab and , if necessary , corticosteroids , to control disease activity . 66 patients assigned to conventional management received corticosteroids , followed , in sequence , by azathioprine and infliximab . The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52 . Analysis was by modified intention to treat . This trial was registered with Clinical Trials.gov , number NCT00554710 . FINDINGS Four patients ( two in each group ) did not receive treatment as per protocol . At week 26 , 39 ( 60.0 % ) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection , compared with 23 ( 35.9 % ) of 64 controls , for an absolute difference of 24.1 % ( 95 % CI 7.3 - 40.8 , p=0.0062 ) . Corresponding rates at week 52 were 40/65 ( 61.5 % ) and 27/64 ( 42.2 % ) ( absolute difference 19.3 % , 95 % CI 2.4 - 36.3 , p=0.0278 ) . 20 of the 65 patients ( 30.8 % ) in the early combined immunosuppression group had serious adverse events , compared with 19 of 64 ( 25.3 % ) controls ( p=1.0 ) . INTERPRETATION Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn 's disease . Initiation of more intensive treatment early in the course of the disease could result in better outcomes Background : The effects of azathioprine ( AZA ) and budesonide ( BUD ) on mucosal healing and histologic remission of Crohn 's disease ( CD ) are insufficiently studied . In this prospect i ve study we evaluated the comparative effects of AZA and BUD on endoscopic and histologic activity in patients with steroid‐dependent Crohn 's ileocolitis or proximal colitis who had achieved clinical remission on conventional steroids . Methods : Patients were r and omized to AZA ( 2.0–2.5 mg/kg a day ) or BUD ( 6–9 mg a day ) for 1 year . The study protocol included clinical examination , laboratory tests , calculation of the Crohn 's Disease Activity Index ( CDAI ) , completion of the Inflammatory Bowel Disease Question naire ( IBDQ ) , at baseline and then every 2 months for 1 year . Ileocolonoscopy with regional biopsies was performed at baseline and then at the end of the study to assess mucosal healing and the histologic activity of CD . Results : Thirty‐eight patients were r and omized to AZA and 39 to BUD . At the end of the study 32 and 25 patients in the AZA and BUD groups , respectively , were in clinical remission ( P = 0.07 ) . The Crohn 's Disease Endoscopic Index of Severity ( CDEIS ) score fell significantly only in the AZA group ( P < 0.0001 ) . Complete or near complete healing was achieved in 83 % of AZA‐treated patients compared with only 24 % of BUD‐treated patients ( P < 0.0001 ) . Histologic activity as assessed by an average histology score ( AHS ) fell significantly only in the AZA group ( P < 0.001 versus baseline ) and was significantly lower than in the BUD group at the end of the study ( P < 0.001 ) . Eight patients in the AZA group were withdrawn for adverse events ( n = 6 ) or relapse of disease compared with 14 patients in the BUD group who were withdrawn for relapse of disease . Conclusions : In patients with steroid‐dependent inflammatory Crohn 's ileocolitis or proximal colitis who achieve clinical remission with conventional steroids , a 1‐year treatment with AZA was superior to BUD in achieving and maintaining mucosal healing and histologic remission Needing a single index of degree of illness in Crohn 's disease , the National Cooperative Crohn 's Disease Study group collected data prospect ively from 187 visits of 112 patients with Crohn 's disease of the small bowel , colon , or both . Information on 18 predictor variables was gathered at each visit . In addition , the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient 's status with that at the previous visit . A multiple regression computer program was utilized to derive an equation for prediction of the physician 's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints . This equation , numerically simplified and utilizing eight selected variables , is the Crohn 's Disease Activity Index . Index values of 150 and below are associated with quiescent disease ; values above that indicate active disease , and values above 450 are seen with extremely severe disease BACKGROUND & AIMS Because the reoperation rate for Crohn 's disease is high after resective surgery , use of conservative surgery has increased . Mesalamine was investigated for the prevention of postoperative relapse , with disappointing results . The role of azathioprine in the postoperative setting is unknown . We aim ed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn 's disease . METHODS In a prospect i ve , open-label , r and omized study , 142 patients received azathioprine  ( 2 mg . kg -1 . day -1 ) or mesalamine ( 3 g/day ) for 24 months . Clinical relapse was defined as the presence of symptoms with a Crohn 's Disease Activity Index score > 200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery . RESULTS After 24 months , the risk of clinical relapse was comparable in the azathioprine and mesalamine groups , both on intention-to-treat ( odds ratio [ OR ] , 2.04 ; 95 % confidence interval [ CI ] , 0.89 - 4.67 ) and per- protocol analyses ( OR , 1.79 ; 95 % CI , 0.80 - 3.97 ) . No difference was observed with respect to surgical relapse at 24 months between the 2 groups . In a subgroup analysis , azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections ( OR , 4.83 ; 95 % CI , 1.47 - 15.8 ) . More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine ( 22 % vs. 8 % ; P = 0.04 ) . CONCLUSIONS While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery , azathioprine is more effective in those patients who have undergone previous intestinal resection Background : Endoscopic recurrence occurs in up to 80 % of patients with Crohn ’s disease 1 year after intestinal resection .  Imidazole antibiotics , thiopurines , and particularly their combination have proven efficacy in preventing endoscopic recurrence . The aim of the study was to compare the efficacy of the addition of metronidazole ( for 3 months after the surgical treatment ) to azathioprine for the prevention of postsurgical endoscopic recurrence . Methods : A pilot study was made of 50 patients with Crohn ’s disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year . The patients were r and omized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months ( n = 25 per arm ) . Endoscopic assessment was performed 6 and 12 months after the surgical resection . The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of < 2 at 6 months . The initial sample size had an 80 % statistical power in detecting an absolute risk reduction of ≥30 % . Results : Endoscopic recurrence occurred in 28 % and 44 % of the patients at 6 months ( P = 0.19 ) and in 36 % and 56 % ( P = 0.15 ) at 12 months in the metronidazole and placebo groups , respectively . No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence ( Rutgeerts score ≥ 3 ) at 6 and 12 months . Likewise , there were no differences in the rate of adverse events between the treatment groups . Conclusions : The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence  beyond azathioprine alone in this study but does not worsen its safety profile BACKGROUND & AIMS An open study reported that patients with Crohn 's disease in remission who have taken azathioprine for longer than 3.5 years are at low risk of relapse when azathioprine is discontinued . To confirm this observation , we performed a multicenter , double-blind , noninferiority withdrawal study . METHODS Patients who were in clinical remission on azathioprine for > or = 42 months were r and omized to continue azathioprine or to receive an equivalent placebo for 18 months . The primary end point was clinical relapse at 18 months . RESULTS Forty patients were r and omly assigned to receive azathioprine and 43 to receive placebo . Characteristics of patients at entry were similar in the 2 study groups . At 18 months , 3 patients had a relapse in the azathioprine group , and 9 had a relapse in the placebo group . Kaplan-Meier estimates of the relapse rate at 18 months were 8 % + /- 4 % and 21 % + /- 6 % , respectively . The hypothesis that placebo was inferior to azathioprine was not rejected ( P = .195 ) . Among the baseline variables , C-reactive protein level > 20 mg/L , time without steroids < 50 months , and hemoglobin level < 12 g/dL were found to be predictive of relapse in the multivariate analysis . CONCLUSIONS This study shows that azathioprine withdrawal is not equivalent to continued therapy with azathioprine for maintenance of remission in patients with Crohn 's disease who have been in remission on azathioprine  for > or = 3.5 years . Thus , azathioprine maintenance therapy should be continued beyond 3.5 years Abstract Twenty-two patients with Crohn 's disease were treated with azathioprine ( 2 mg . per kg . per day ) or placebo in a double-blind controlled trial lasting 24 weeks . Twelve acutely ill patients received a course of prednisolone adequate to ensure early remission ( group I ) , and ten out patients were already in a remission induced and maintained by prednisolone ( group II ) . Ten of eleven patients on azathioprine remained in remission and completed the trial , whereas eight of eleven receiving placebo were withdrawn early because of relapse . The mean interval between discontinuation of prednisolone and completion of or withdrawal from the trial was 10·7 weeks for patients on azathioprine and 4·0 weeks for those on placebo . Clinical estimates of improvement and continued remission  in azathioprine-treated patients of groups I and II were confirmed by " disease-activity scores " compiled from clinical and laboratory data OBJECTIVES : A prospect i ve study was undertaken to compare the efficacy of everolimus versus azathioprine or placebo in maintaining steroid-induced remission in active Crohn 's disease ( CD ) and assess the safety and pharmacokinetics of everolimus . METHODS : This was a r and omized , double-blind , placebo-controlled , proof-of-concept study in adults with moderate-to-severe active CD . The patients received oral steroids for a rapid induction of remission plus everolimus 6 mg/day , azathioprine 2.5 mg/kg/day , or placebo as maintenance treatment . The main outcome measure was the treatment success , defined as a steroid-free remission by the end of month 3 and maintained until study cutoff without the use of prohibited efficacy treatments . RESULTS : Following an interim analysis , the study was terminated before enrollment was completed due to the lack of efficacy . The full intent-to-treat population comprised 138 patients . Only 96 patients who entered the study ≥7 months prior to data cutoff were included in the primary efficacy population .  The treatment success was achieved in 13 of 38 everolimus patients , 22 of 36 azathioprine patients , and 8 of 22 placebo patients . Using the Kaplan – Meier estimates at month 7 , the incidence of treatment success was 22.0 % with everolimus group ( 95 % confidence interval [ CI ] 6.7–37.3 % , P = 0.610 vs placebo ) , 38.3 % with azathioprine group ( 95 % CI 20.6–55.9 % , P = 0.500 vs placebo ) , and 28.8 % with placebo group ( 95 % CI 7.7–49.9 % ) . The type and incidence of adverse events  in the everolimus cohort were similar to those reported in the approved transplantation indications . CONCLUSIONS : The safety and tolerability  of everolimus ( 6 mg/day ) in patients with active CD were comparable to azathioprine . At this dose , everolimus is not more efficacious in achieving a steroid-free remission in active CD than the comparators BACKGROUND & AIMS A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohn 's disease , yet little is known about the efficacy of early thiopurine therapy in adults . METHODS We performed a prospect i ve double-blind trial of adult patients with a recent ( < 8 weeks ) diagnosis of Crohn 's disease . Patients were r and omly assigned to groups given azathioprine ( 2.5 mg · kg(-1 ) · day(-1 ) , n = 68 ) or placebo ( n = 63 ) at 31 hospitals from February 2006 to September 2009 .  Corticosteroids but no other concomitant medications were allowed for control of disease activity . The primary measure of efficacy was sustained corticosteroid-free remission . RESULTS After 76 weeks of treatment , 30 patients treated with azathioprine ( 44.1 % ) and 23 given placebo ( 36.5 % ) were in sustained corticosteroid-free remission ( difference of 7.6 % ; 95 % confidence interval , -9.2 to 24.4 % ; P = .48 ) . The rates of relapse ( defined as Crohn 's Disease Activity Index score > 175 ) and corticosteroid requirements were similar between groups . A post hoc analysis of relapse , defined as a Crohn 's Disease Activity Index score > 220 , showed lower relapse rates in the azathioprine group than in the placebo group ( 11.8 % vs 30.2 % ; P = .01 ) . Serious adverse events occurred in 14 patients in the azathioprine group ( 20.6 % ) and 7 in the placebo group ( 11.1 % ) ( P = .16 ) . A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation ( 20.6 % ) than in the placebo group ( 6.35 % ) ( P = .02 ) . CONCLUSIONS In a study of adults with Crohn 's disease , early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis . EudraCT 2005 - 001186 - 34 What is meant by intention-to-treat ? Why should data be analyzed in controlled trials in a way that all participants are included in the group to which they were r and omly assigned , regardless of whether they completed the intervention given to the group ? In this Tutorial , the logic of the intention-to-treat principle is outlined . It is shown that study results may be biased by excluding patients post hoc thus producing spurious effects that do not exist in the population under study . The intention-to-treat strategy avoids this bias
BACKGROUND The therapeutic role of 6-mercaptopurine ( 6-MP ) and azathioprine ( AZA ) remains controversial due to their perceived relatively slow-acting effect and adverse effects .
An up date d meta- analysis was performed to evaluate the efficacy of these agents for the maintenance of remission in quiescent Crohn 's disease .
OBJECTIVES To assess the efficacy of AZA and 6-MP for maintenance of remission in quiescent Crohn 's disease .