Comparison of twice-daily inhaled ciclesonide and fluticasone propionate in patients with moderate-to-severe persistent asthma

OBJECTIVE: To investigate the relative efficacy of ciclesonide and fluticasone propionate (FP) administered at comparable microgram doses in maintaining asthma control in patients with moderate-to-severe persistent asthma. METHODS: This randomized, open-label, parallel-group study enrolled patients aged 12-75 years with a 6-month history of bronchial asthma. To enter a 2-week run-in period, patients had to have received FP 500-1000 microg/day or equivalent at a stable dose for 4 weeks and have a forced expiratory volume in 1s (FEV 1) 80% of predicted. To enter the treatment period, patients had to have the following during run-in: FEV 1 80% of predicted; reversibility of Delta FEV 1 12% after 200-400 microg salbutamol; and 1 day without asthma symptoms during the last 7 days. Patients were randomized to twice-daily ciclesonide 320 microg (ex-actuator) or twice-daily FP 330 microg (ex-actuator) for 6 months. Efficacy was assessed by lung function, asthma exacerbations, asthma symptoms and rescue medication use. Patients completed the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Adverse events (AEs), including local oropharyngeal AEs, were recorded. RESULTS: 528 patients were randomized (ciclesonide, n=255; FP, n=273). In both groups, FEV 1 was maintained from baseline to study end (mean increase: ciclesonide 11 mL, FP 24 mL; intention-to-treat [ITT] analysis). The least squares mean+/-standard error of the mean for the treatment difference was -13+/-29 (95% confidence interval [CI]: -70, 44) in the ITT analysis and -27+/-34 (95% CI: -93, 40) in the per-protocol (PP) analysis, demonstrating non-inferiority of ciclesonide to FP. Morning, evening and site-measured PEF improved significantly with both treatments (ITT and PP analyses: p<0.05). Six patients receiving ciclesonide and seven receiving FP (ITT analysis) experienced an asthma exacerbation requiring treatment with oral corticosteroids. Both treatments significantly decreased asthma symptom score sum (ITT and PP analyses: p0.0001) and rescue medication use (ITT and PP analyses: p<0.05), with no significant difference between treatments. Both treatments significantly improved overall AQLQ(S) score (ITT and PP analyses: p<0.05). Significantly more patients experienced candidiasis and dysphonia with FP compared with ciclesonide (p=0.0023). CONCLUSION: Ciclesonide 320 microg and FP 330 microg administered twice daily over 6 months provided similar efficacy in patients with moderate or severe persistent asthma previously well-controlled by high doses of ICS at baseline. Ciclesonide was associated with fewer local AEs than FP.     

A randomized study comparing ciclesonide and fluticasone propionate in patients with moderate persistent asthma

OBJECTIVE: To compare the effects of once-daily ciclesonide and twice-daily fluticasone propionate in patients with moderate persistent asthma. METHODS: Patients aged 12-75 years with moderate bronchial asthma entered a 1-4 week run-in period. For inclusion into the 12-week, randomized, open-label treatment period, patients had to have a forced expiratory volume in 1s (FEV1) of either 60-80% of predicted or 80% of predicted and a defined use of rescue medication and asthma symptoms, depending on previous treatment. Patients received ciclesonide 320 microg once daily (ex-actuator) or fluticasone propionate 200 microg twice daily. Primary efficacy endpoint was change from baseline in FEV1. RESULTS: In total, 474 patients were randomized. FEV1 increased significantly from baseline with ciclesonide and fluticasone propionate in the intention-to-treat (ITT) and per-protocol (PP) analyses (all p < 0.0001). Treatment difference was -31 mL (95% confidence interval [CI]: -121, 59) in the PP analysis, demonstrating non-inferiority of ciclesonide. Similar findings were seen for other measures of lung function. In the ITT population, asthma symptom scores and rescue medication use decreased with both treatments (all p < 0.0001). Improvement in health-related quality of life (HRQoL) from baseline was significantly greater with ciclesonide than fluticasone (p = 0.005; one-sided). There were no cases of oral candidiasis in patients receiving ciclesonide and nine cases (3.8%) in those receiving fluticasone propionate (p = 0.002; one-sided). CONCLUSIONS: Treatment with once-daily ciclesonide and twice-daily fluticasone propionate resulted in similar improvements in lung function in patients with moderate persistent asthma. Ciclesonide showed significant improvements in oral candidiasis and HRQoL over fluticasone.     

ERCP is safe and effective in patients 80 years of age and older compared with younger patients

BACKGROUND: Biliary disease frequently occurs in the elderly, but there are limited data on ERCP in the elderly population. PATIENTS: A total of 502 patients (group A, 97; group B, 405) underwent 724 ERCP procedures. MAIN OUTCOME MEASUREMENTS: All consecutive ERCPs performed between 2000 and 2002 at a single center were retrospectively reviewed for patients >/=80 years old (group A) and patients <80 years old (group B) to evaluate endoscopic findings, interventions, complications, and mortality related to complications. RESULTS: The number of important chronic concomitant diseases was significantly higher in the older group (average per patient 1.08 vs 0.57, P < .001). Successful cannulation was achieved in 88% in group A versus 86% in group B, and endoscopic sphincterotomy was performed in 63.2% versus 51.4%. Periampullary diverticulum was found significantly more often in patients of group A (39.2%) than of group B (14.1%, P < .001). Stents were used in 24.1% of ERCP procedures in group A and in 22.9% in group B. There was no significant difference in the complication rate between group A (6.8%) and group B (5.1%) and in early mortality (1.03% vs 0.25%), respectively. CONCLUSION: ERCP is a safe and effective intervention in the elderly because complication and early mortality rates are comparable to those of younger patients, although comorbidity is significantly higher.     

Randomized comparison of ciclesonide 160 and 640 microg/day in severe asthma

OBJECTIVE: Demonstrating clinical benefit of higher doses of inhaled corticosteroids in asthma is frequently problematic owing to their relatively flat dose-response curve in this condition. In this study we compared the efficacy and safety of a fourfold difference in the dose of ciclesonide-ciclesonide 320 microg twice daily (CIC640) versus ciclesonide 160 microg once daily (CIC160)-in patients with severe persistent asthma. METHODS: Patients with bronchial asthma (6 months) were included in this randomized, double-blind study. After receiving fluticasone propionate 250 microg twice daily during run-in, patients were randomized to CIC160 (n=339) or CIC640 (n=341) for 12 weeks. Primary endpoints were time to first asthma exacerbation and forced expiratory volume in 1s (FEV(1)). Secondary endpoints included other lung function variables, asthma symptom scores and rescue medication use (RMU). RESULTS: Asthma exacerbations occurred in 12.7% of patients receiving CIC160 and 6.7% receiving CIC640. CIC640 was superior for time to first exacerbation (p=0.0050, one-sided). FEV(1) increased significantly with CIC160 and CIC640 (least squares mean+/-SE of mean: 269+/-31 and 332+/-31 mL, respectively; p<0.0001), with no significant difference between groups. Change in % predicted FEV(1) and morning peak expiratory flow (PEF) were significantly higher with CIC640 (p<0.05). Asthma symptom score sums and RMU decreased in both groups; CIC640 was statistically superior (p=0.0108 and 0.0005, respectively). No unexpected adverse events were reported in either group and the majority of the events reported were mild or moderate in intensity. No significant changes in serum cortisol were observed from the baseline to the study end. Small decreases in creatinine-adjusted 24h urine cortisol levels from baseline were seen in both the treatment groups, which, due to the large patient numbers, were statistically significant (p<0.05); however, no dose-response effect was seen and the difference between groups was not significant (p=0.7892). CONCLUSION: CIC640 was superior to CIC160 for time to first exacerbation, % predicted FEV1, morning PEF, asthma symptom score sum and RMU in patients with severe asthma; both doses had similar tolerability profiles and no significant changes in serum cortisol were seen in either treatment group.     

A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma

Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.     

Similar efficacy of ciclesonide once daily versus fluticasone propionate twice daily in patients with persistent asthma.

This 12-week, double-blind, parallel-group study compared the efficacy and safety of once daily ciclesonide and twice daily fluticasone propionate in patients aged 12-75 years with persistent asthma. Patients were randomized to once-daily ciclesonide 80 micro g (n = 278) or 160 micro g (n = 271), or twice daily fluticasone propionate 88 micro g (n = 259) (all ex-actuator). Significant improvements from baseline were seen in all three treatment groups for forced expiratory volume in 1 second, asthma symptom scores and rescue medication use (all p < 0.0001). Asthma exacerbation rates were low (each ciclesonide group, n = 2; fluticasone group, n = 1). Adverse event reporting indicated good tolerability. Once daily ciclesonide 80 micro g or 160 micro g showed comparable efficacy and tolerability to twice daily fluticasone propionate 88 micro g in persistent asthma.     

Salmeterol/fluticasone propionate (50/100 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in children with asthma

The aim of this study was to compare the efficacy and safety in children of salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice daily) when delivered together via a single Diskus inhaler (Seretide; combination therapy) or concurrently using two separate Diskus inhalers (concurrent therapy). In a multicenter, randomized, double-blind, double-dummy, parallel-group study, 257 children with reversible airways obstruction who remained symptomatic on inhaled corticosteroids (200-500 microg daily) alone were randomized to combination or concurrent therapy for 12 weeks. Efficacy was assessed by measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol use. In addition, lung function tests were performed at each clinic visit. Safety assessments included monitoring of adverse events and morning serum cortisol concentrations. The primary efficacy parameter (mean morning PEF) increased during treatment in both groups; adjusted mean changes were 33 and 28 L/min for the combination and concurrent therapies, respectively. The 90% confidence interval for the difference in mean morning PEF between treatment groups was within the +15 L/min criterion for clinical equivalence. Similarly, there were improvements in pulmonary function, symptom score, and rescue salbutamol use during treatment in both groups, with no significant differences between the combination and concurrent therapy groups for any of these secondary efficacy parameters. Both treatment regimens were well-tolerated and had comparable adverse event profiles. Mean morning serum cortisol levels increased similarly in both groups during the study. In conclusion, salmeterol and fluticasone propionate therapy given as a new combination product is as safe and effective in children with asthma as the same drugs given concurrently via separate inhalers.     

Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma

Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.     

Comparative efficacy of once-daily ciclesonide and budesonide in the treatment of persistent asthma

BACKGROUND: The aim of this study was to compare the efficacy and safety of once-daily ciclesonide, a new-generation, on-site-activated, inhaled corticosteroid, with once-daily budesonide in persistent asthma. METHODS: Eligible patients requiring budesonide or equivalent 320-640 microg (ex-mouthpiece, equivalent to 400-800 microg; Turbohalertrade mark) daily entered a 2-week baseline, and then a 2- to 4-week pretreatment period (budesonide 1280 microg/day; ex-mouthpiece, equivalent to 1600 microg/day). Patients with an increase in forced expiratory volume in 1s (FEV1) of 7% or 0.15 L were randomised to ciclesonide 320 microg (ex-actuator, equivalent to 400 microg ex-valve) via a hydrofluoroalkane-metered dose inhaler (HFA-MDI) without a spacer or budesonide 320 microg once daily in the morning for 12 weeks. Change in FEV1 was the primary endpoint. RESULTS: In all, 359 patients were randomised. The FEV1 and forced vital capacity (FVC) decreased by 0.18 and 0.12L, respectively, in the ciclesonide group, and by 0.23 and 0.21L in the budesonide group. For FEV1, ciclesonide was noninferior and numerically superior to budesonide. For FVC, ciclesonide was statistically superior to budesonide (P=0.010). Asthma symptom scores were comparable; the median percentage of symptom-free days was significantly higher for ciclesonide (43.6%) versus budesonide (25.8%) (P=0.017). Rescue medication use decreased significantly only for ciclesonide patients (P=0.009). Frequency of adverse events was low in both groups. CONCLUSION: Ciclesonide 320 microg once daily by HFA-MDI without a spacer was at least as effective as budesonide 320 microg once daily in persistent asthma.     

Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma

Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.     

Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) is effective and safe in adults previously treated with inhaled corticosteroids.

This 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of budesonide 400 microg administered once daily via Turbuhaler in adults previously treated with at least twice-daily dosing of inhaled corticosteroids. Pulmonary function (FEV1, PEF, FVC, FEF(25-75%)), asthma symptom scores, quality of life, and breakthrough medication use were significantly (p < 0.05) different in patients receiving once-daily budesonide Turbuhaler compared to placebo, and significantly (p < 0.001) more patients receiving placebo discontinued the study. Adverse events were similar between study groups. Once-daily administration of budesonide Turbuhaler was safe and efficacious in patients previously treated with inhaled corticosteroids.     

Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease--a long-term follow-up

OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18) or steroid-refractory (n = 35) IBD, Crohn's disease (CD) (n = 11), ulcerative colitis (UC) (n = 40), or pouchitis (PC) (n = 2) were reviewed. Tacrolimus (0.1 mg/kg body weight per day) was administered orally in all and initially intravenously in 2 patients (0.01 mg/kg body weight per day), aiming for serum trough levels of 4-8 ng/mL. Forty-one of 53 (77.1%) patients were receiving concomitant azathioprine. The mean treatment duration was 25.2 +/- 4.6 SD months (0.43-164 months). Patients were followed for a mean of 39 +/- 4.1 SD months (5-164 months). Response was evaluated using a modified clinical activity index (M-CAI). RESULTS: Thirty-one UC (78%), 10 CD (90.1%), and both PC (100%) patients experienced an immediate clinical response or went into remission at 30 days. A statistically significant drop on the M-CAI was documented for UC and CD patients. Nine UC patients (22.5%) underwent colectomy between 1.6 and 41.3 months following initiation. Mean colectomy-free survival was 104.8 +/- 15.5 (95% CI 74.4-135.2) months (limited to 164.4 months). Cumulative colectomy-free survival was estimated 56.5% at 43.8 months. Steroids were reduced or discontinued in 40 of 45 UC and CD patients (90%) taking steroids. Side effects included a temporary rise of creatinine (n = 4, 7.6%), tremor or paresthesias (n = 5, 9.4%), hyperkalemia (n = 1, 1.9%), hypertension (n = 1, 1.9%), and opportunistic infections (n = 2, 3.8%). CONCLUSION: Long-term tacrolimus therapy appears safe and effective in refractory IBD.     

Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma

AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between patients ≥ 75 years old and younger patients (aged between 65 and 75 years and younger than 65 years) with hepatocellular carcinoma (HCC), diagnosed according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases criteria. The decision that patients were not candidates for curative therapy was made by a multidisciplinary HCC team. Data collected included demographics, co-morbidities, liver disease etiology, liver disease severity and the number of procedures. The primary outcome was mortality; secondary outcomes included post-embolization syndrome (nausea, fever, abdominal right upper quadrant pain, increase in liver enzymes with no evidence of sepsis and with a clinical course limited to 3-4 d post procedure) and 30-d complications. Additionally, changes in liver enzyme measurements were assessed [alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transpeptidase and alkaline phosphatase] in the week following TACE. Analysis employed both univariate and multivariate methods (Cox regression models). RESULTS: Of 102 patients who underwent TACE as sole treatment, 10 patients (9.8%) were > 80 years old at diagnosis; 13 (12.7%) were between 75 and 80 years, 45 (44.1%) were between 65 and 75 years and 34 (33.3%) were younger than 65 years. Survival analysis demonstrated similar survival patterns between the elderly patients and younger patients. Age was also not associated with the adverse event rate. Survival rates at 1, 2 and 3 years from diagnosis were 74%, 37% and 31% among patients < 65 years; 83%, 66% and 48% among patients aged 65 to 75 years; and 86%, 41% and 23% among patients ≥ 75 years. There were no differences between the age groups in the pre-procedural care, including preventive treatment for contrast ne     

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for the BM dysfunction seen in patients with Shwachman-Diamond syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced-intensity-conditioning protocol in seven patients with SDS and BM aplasia or myelodysplastic syndrome/AML. The preparative regimen consisted of Campath-1H, fludarabine and melphalan. Four patients received matched related marrow and three received unrelated stem cells (two PBSCs and one marrow). All but one was 8 of 8 allele HLA matched. All patients established 100% donor-derived hematopoiesis. No patient in this cohort developed grades III-IV GVHD. One patient had grade II skin GVHD that responded to systemic corticosteroids and one had grade I skin GVHD, treated with topical corticosteroids. Two out of seven patients developed bacterial infections in the early post transplant period. Viral infections were seen in four out of seven patients and were successfully treated with appropriate antiviral therapy. All patients are currently alive. These data indicate that HSCT with reduced-intensity conditioning is feasible in patients with SDS and associated with excellent donor cell engraftment and modest morbidity.     

Ciclesonide is more effective than budesonide in the treatment of persistent asthma

BACKGROUND: Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. METHODS: A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. RESULTS: Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels. CONCLUSION: Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.     

Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis

Background. 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6–1.2mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase (TPMT) mutation in the Japanese population. Methods. Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. Results. Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50mg/day of 6-MP or 100mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30mg/day of 6-MP or 50mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5–10mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. Conclusions. A dose of 50mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.