GASTROENTEROLOGY 1996;110:1713–1718
`
`Oral Budesonide Versus Prednisolone in Patients With Active
`Extensive and Left-Sided Ulcerative Colitis
`
`ROBERT LO¨ FBERG,* A˚ KE DANIELSSON,‡ OLE SUHR,‡ A˚ KE NILSSON,§ RUDOLF SCHIO¨ LER,㛳
`ANDERS NYBERG,Ø ROLF HULTCRANTZ,# BO KOLLBERG,** ROLF GILLBERG,‡‡ ROGER WILLE´N,§§
`TORE PERSSON,㛳 㛳 and LARS SALDE㛳 㛳
`*Department of Gastroenterology, Huddinge University Hospital, Stockholm; ‡Department of Medicine, University Hospital, Umea˚; §University
`Hospital, Lund; ØAcademic Hospital, Uppsala; #Karolinska Hospital, Stockholm; **Danderyd Hospital, Stockholm; ‡‡Sahlgrenska Hospital,
`Gothenburg; 㛳Department of Surgery, Ryhov Hospital, Jo¨nko¨ping; §§Department of Pathology, University Hospital, Lund; and 㛳 㛳Astra Draco AB,
`Lund, Sweden
`
`See editorial on page 2000.
`
`Background & Aims: Systemic glucocorticosteroids
`(GCSs) have proven efficacy in active ulcerative colitis
`but cause undesired systemic side effects. Therefore,
`new GCSs with high topical activity and a high rate of
`metabolism may be of clinical value in this condition.
`The aim of this study was to explore the efficacy and
`safety of the topically acting GCS budesonide in an
`oral controlled-release formulation in extensive or left-
`sided, mild to moderately active ulcerative colitis.
`Methods: A 9-week, randomized, double-blind, con-
`trolled trial was performed, and treatments with 10 mg
`budesonide or 40 mg prednisolone daily, both gradually
`tapered, were compared. Endoscopic improvement and
`effect on endogenous plasma cortisol were assessed.
`Results: Thirty-four patients were administered bude-
`sonide, and 38 patients were administered predniso-
`lone. Mean endoscopic scores improved significantly in
`both groups but without difference between the groups.
`Five patients in the budesonide group and 7 patients
`in the prednisolone group deteriorated and were with-
`drawn from the study. Morning plasma cortisol levels
`were suppressed in the prednisolone group (entry, 449
`nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L)
`but were unchanged in the budesonide group. Conclu-
`sions: The GCS budesonide administered in an oral
`controlled-release formulation seems to give an overall
`treatment result in active ulcerative colitis approaching
`that of prednisolone but without suppression of plasma
`cortisol levels. This concept merits further evaluation.
`
`B
`
`udesonide is a highly potent glucocorticosteroid
`(GCS) with a high affinity for the GCS receptor. It
`is readily absorbed and rapidly degraded to metabolites
`with low GCS activity during the first passage through
`the liver1 and, thus, has a low systemic availability. Bude-
`sonide in enema form (2 mg/100 mL) has been evaluated
`for use in active distal ulcerative colitis (UC) and proctitis
`
`and has been proven to be superior to placebo2 and to
`be as efficacious as conventional prednisolone3 – 5 or me-
`salamine retention enemas.6 No, or only limited, suppres-
`sion of endogenous plasma cortisol has been noted.2 – 5
`An oral formulation of budesonide optimized to release
`the drug in the ileum and ascending colon has been
`developed for the treatment of Crohn’s disease. This for-
`mulation has been shown to be superior to placebo7 and
`comparable with oral prednisolone8 but causes signifi-
`cantly fewer GCS-associated side effects.
`In severe to moderately severe attacks of UC, conven-
`tional GCSs have been proven to be the most efficacious
`medical treatment to induce remission and to alleviate
`symptoms.9 In moderately severe attacks of UC, a course
`of oral prednisolone or prednisone is usually the therapy
`of choice, with or without concomitant mesalamine or
`sulfasalazine treatment.
`The aim of this explorative pilot study was to evaluate
`the efficacy of an oral formulation of budesonide, opti-
`mized to release the drug throughout the colon, vs. a
`standard regimen of oral prednisolone in the treatment
`of active extensive and left-sided UC. Furthermore, the
`safety and tolerability of budesonide was evaluated, in-
`cluding the impact on endogenous plasma cortisol pro-
`duction.
`
`Patients and Methods
`Patients
`
`Both hospitalized patients and outpatients, aged at
`least 18 years, were eligible for inclusion. All patients gave
`their informed signed consent before entry. Criteria for inclu-
`sion were a definite diagnosis of mild to moderately severe
`active UC extending proximally beyond the sigmoid colon as
`verified by colonoscopy at entry. Endoscopic activity had to
`
`Abbreviation used in this paper: GCS, glucocorticosteroid.
`䉷 1996 by the American Gastroenterological Association
`0016-5085/96/$3.00
`
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`1714 LO¨ FBERG ET AL.
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`GASTROENTEROLOGY Vol. 110, No. 6
`
`be a score of at least 2 (see below) in one or more colorectal
`segments, and disease symptoms had to include blood in stools
`and at least three bowel movements per day before entry (ex-
`cluding days before colonoscopy).
`Exclusion criteria included diabetes, untreated hyperten-
`sion, and clinically significant liver disease. Patients being
`treated with H2-receptor antagonists or proton pump inhibi-
`tors and patients who had been administered GCSs other than
`oral contraceptives during the 2 weeks preceding the trial were
`also excluded. A history of GCS hypersensitivity, pregnancy,
`and breast-feeding were also exclusion criteria.
`Concomitant therapy for UC was not allowed, with the
`exception of oral sulfasalazine, mesalamine formulations, or
`olsalazine. If any of these drugs were used, the dose had to be
`kept constant during the last 2 weeks before and throughout
`the trial. Other drugs necessary for the patient’s well-being
`were administered at the discretion of the investigator.
`
`Investigational Drugs
`
`Budesonide capsules and the corresponding placebo
`were manufactured by Astra Draco AB (Lund, Sweden). The
`capsules contained acid-resistant pellets with a sustained-re-
`lease profile to deliver the active drug during the passage
`throughout the colon. The reference drugs, prednisolone tab-
`lets (2.5, 5.0, and 10 mg) and placebo tablets, were manufac-
`tured by Hydro Pharma A.S. (Elverum, Norway). The drugs
`were delivered in blister packages, and the patients were ad-
`ministered one dose in the morning (containing budesonide
`capsules and placebo prednisolone tablets or vice versa) and
`one dose in the evening (containing either a budesonide capsule
`or a placebo budesonide capsule). During the last 2 weeks of
`the study, only a morning dose was administered.
`
`Study Design and Treatment Plan
`
`The study was of randomized, double-blind, double-
`dummy design with two parallel groups, and the total treat-
`ment time was 9 weeks. The patients were randomly allocated
`to treatment with either oral budesonide or oral prednisolone
`from blocks of four at each of the participating nine centers.
`Budesonide was administered in a dose of 6 mg in the
`morning and 4 mg in the evening during the first 4 weeks
`and was tapered to 4 mg in the morning and 4 mg in the
`evening during treatment weeks 5–7 and to 4 mg in the
`morning during weeks 8–9. Prednisolone was administered
`as a single morning dose throughout the study, starting with
`40 mg daily during the first 2 weeks and then was tapered by
`5 mg per week until week 8, when 7.5 mg was administered
`as one daily dose with a final dose of 5 mg daily during week
`9. The patients were followed up as outpatients with visits to
`the clinics after 2, 4, and 9 weeks. Patients were withdrawn
`from the study if their clinical status seriously deteriorated or
`if no improvement at all was observed after 2 weeks. Other
`reasons for treatment discontinuation were serious complica-
`tions, adverse events, or pregnancy.
`The patients were asked to return all unused medication at
`each visit to the clinic, and compliance was checked by count-
`
`Table 1. Scoring of Endoscopic Inflammation at
`Colonoscopy and Flexible or Rigid Sigmoidoscopy
`
`Score
`
`0
`1
`2
`3
`
`Endoscopic findings
`
`Normal/noninflamed mucosa
`Granularity, edema, and lack of normal vascular pattern
`Hyperemia, friability, and petechiae (and all of score 1)
`Ulcerations (and all of score 1 and 2)
`
`NOTE. The scores were subdivided as moderate or intense by the
`investigator.
`
`ing unopened blisters at the local hospital pharmacy. Patients
`were considered compliant if they had taken at least 75% of
`the medication.
`
`Assessments
`
`Clinical symptoms. Diary cards were used for registra-
`tion of daily bowel movements (i.e., number of movements,
`quality of stools, and presence of blood and/or mucus). Data
`from the days before colonoscopy were not used in the analysis.
`Endoscopy. Disease extent and severity of mucosal in-
`flammation were assessed by the use of flexible colonoscopy
`at entry and after 4 weeks of treatment. A flexible or rigid
`sigmoidoscopy was performed after 2 and 9 weeks of treatment.
`The macroscopic appearance of the mucosa was classified using
`a four-grade scoring system2,3,5 (Table 1) in each of five prede-
`termined colorectal segments at colonoscopy (ascending colon,
`transverse colon, descending colon, sigmoid colon, and rectum)
`or in the sigmoid colon and/or the rectum at sigmoidoscopy.
`Histopathology. Mucosal biopsy specimens were ob-
`tained from each segment of the colon and rectum and always
`from the most severely affected area in each segment. Biopsy
`specimens were fixed in formalin, embedded in paraffin, stained
`with H&E, and evaluated in a blinded manner by an indepen-
`dent histopathologist (R.W.). The degree of inflammation in
`the histological specimens was then graded according to Flore´n
`et al.10 In this scale, a score of 1 represents essentially normal
`mucosa, and a score of 5 represents the most severe inflamma-
`tory changes.
`Clinical chemistry and hematology. Blood samples for
`assessment of hematology (erythrocyte sedimentation rate, he-
`moglobin, erythrocyte count, and leukocyte count with differ-
`entials and platelets) were taken at entry and after 2, 4, and
`9 weeks. Assessment also included determination of blood
`glucose, serum orosomucoid, albumin, and creatinine levels,
`as well as liver function tests. Morning blood samples (taken
`between 7 and 9:30 AM) were drawn at each visit for analysis
`of plasma cortisol. These samples were frozen and later analyzed
`at one central laboratory (Astra Draco AB) using a high-perfor-
`mance liquid chromatography method.11
`
`Statistical and Ethical Considerations
`
`The primary study variables were the changes in endo-
`scopic and histopathologic scores and in laboratory parameters.
`In the primary analysis, the endoscopic scores from the five
`
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`June 1996
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`ORAL BUDESONIDE IN ULCERATIVE COLITIS 1715
`
`Table 2. Demography and Disease History in Patients
`Treated With Either Oral Budesonide or
`Prednisolone for Active UC
`
`No. of patients
`Sex (M/F)
`Agea (yr; range)
`Duration of UCa (yr; range)
`Current attacka (day; range)
`Involvement
`Extensive colitis
`Left-sided colitis
`Maintenance treatment with
`mesalamine drugs
`(%; median dose [g])
`
`Budesonide
`
`Prednisolone
`
`34
`21/13
`33 (18–67)
`0.8 (0–39)
`34 (0–100/)
`
`38
`21/17
`34 (19–71)
`2.2 (0–23)
`43 (1–100/)
`
`21
`13
`
`22
`16
`
`20 (59; 2.0)
`
`18 (47; 2.0)
`
`aValues are expressed as the median.
`
`different colorectal segments for each patient were reduced to
`one by taking the maximum. The histopathologic scores were
`analyzed in the same way.
`Endoscopic remission was defined as a score of 0, and histo-
`pathologic remission was defined as a score of 1. Responders
`were defined as those patients whose scores were reduced com-
`pared with those at entry. Remission and response rates were
`analyzed after 4 weeks. Clinical symptoms, as recorded in the
`patients’ diaries, were reduced to averages over 2-week periods.
`Changes in laboratory parameters and in clinical symptoms
`were secondary variables.
`The study was designed to have 80% probability of de-
`tecting a difference of about 0.8 in the change of endoscopic
`score with Wilcoxon rank sum test at the 5% level. This
`goal was not based on clinical relevance but seemed realistic
`compared with previous studies with GCS enema preparations
`in UC.2 – 5 Furthermore, in those studies, the use of the endo-
`scopic scoring system showed that endoscopic improvement
`correlated well with both clinical and histological improve-
`ment, as well as with remission rates. The calculation was
`based on 20 evaluable patients per group. It was decided that
`a group size of 35 patients would be used to compensate for
`early withdrawals.
`The primary analysis was based on the all-patients-treated
`and the last-value-extended principles. For endoscopic and his-
`topathologic scores, two-way analysis of variance was applied
`to the changes from entry with the factors treatment, time,
`and treatment by time. x2 tests (with Yates’ correction) were
`used for the analysis of remission and response rates and for
`the proportion of plasma cortisol values of õ150 nmol/L.
`Student’s t test was used for all other variables. P values of
`°0.05 were considered statistically significant.
`Because this was a pilot study with mainly an exploratory
`purpose and no aim of proving differences, no compensation
`for multiple comparisons was made.
`The study was performed in accordance with the principles
`stated in the Declaration of Helsinki, and approvals from the
`Swedish Medical Products’ Agency and the local Ethics Com-
`mittees were obtained before the trial started.
`
`Results
`Patient Enrollment and Treatment
`Discontinuations
`
`A total of 75 patients were randomized, and 72
`patients were actually treated with one of the study
`drugs. The study groups were well matched with respect
`to age, sex, length of current attack, disease extent, and
`maintenance treatment (Table 2). Of the 38 patients
`receiving mesalamine maintenance therapy, 1 patient was
`treated with mesalazine (Pentasa; Ferring AB, Malmo¨,
`Sweden), 3 patients with olsalazine (Dipentum; Phar-
`macia AB, Uppsala, Sweden), and 34 patients with sulfa-
`salazine (Salazopyrin; Pharmacia AB).
`Thirty-four patients were treated with budesonide,
`and 38 patients were treated with prednisolone. Sixteen
`patients, 8 in each group, were withdrawn from the
`study. The reasons for treatment discontinuations are
`shown in Table 3. No patient was considered noncompli-
`ant.
`
`Efficacy
`
`The mean endoscopic scores are shown in Figure
`1. The mean decreased with time significantly in both
`groups. After 9 weeks, the mean decrease was 1.20 in
`the budesonide group compared with 1.36 in the pred-
`nisolone group (P Å 0.12; two-way analysis of variance).
`When the scores were analyzed separately for each of the
`five colorectal segments, a significantly greater improve-
`ment was observed in the sigmoid colon for the predniso-
`lone group after 4 weeks (P Å 0.04) (Figure 2). The 95%
`confidence intervals for the differences in the decrease
`of the endoscopic scores between the budesonide and
`prednisolone groups were 00.1 to /0.8 at 2 weeks, 00.2
`to /0.8 at 4 weeks, and 00.4 to /0.7 at 9 weeks.
`The corresponding confidence intervals for the changes
`in histological scores were 0.1–1.2, 0.1–1.3, and 0.0–
`1.4. Negative values represent better efficacy for bude-
`sonide.
`Four of 31 patients remaining in the budesonide group
`after 4 weeks were in endoscopic remission (defined as
`an endoscopic score of 0 in all colonic segments) com-
`
`Table 3. Reasons for Treatment Discontinuations in 16
`Patients
`
`Reason
`
`Budesonide
`
`Prednisolone
`
`Disease deterioration
`Adverse event
`Withdrawal of informed consent
`
`5
`2a
`1
`
`aRash in 1 patient and vomiting in 1 patient.
`bInsomnia.
`
`7
`1b
`0
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`1716 LO¨ FBERG ET AL.
`
`GASTROENTEROLOGY Vol. 110, No. 6
`
`Figure 1. The effect of budesonide capsules (
`) and prednisolone
`tablets (–rr–rr–) on the mean endoscopic scores (from entry to 2,
`4, and 9 weeks). All patients treated and last-value-extended principle.
`Values are expressed as mean { SEM.
`
`Figure 3. The effect of budesonide capsules (
`) and prednisolone
`tablets (–rr–rr–) on the mean histological scores (from entry to 2,
`4, and 9 weeks). All patients treated and last-value-extended principle.
`Values are expressed as mean { SEM.
`
`pared with 6 of 36 patients in the prednisolone group
`(P Å 0.93). At the same time, 21 patients in the bude-
`sonide group were classified as responders compared with
`25 patients in the prednisolone group (P Å 1.00). There
`were no significant differences in the endoscopic scores
`between patients with extensive or left-sided colitis. The
`histopathologic scores were significantly reduced com-
`pared with baseline in both treatment groups. The reduc-
`tion in histopathologic scores was significantly greater
`in the prednisolone group (P Å 0.022; two-way analysis
`of variance) (Figure 3). A separate analysis for each of
`the colorectal segments showed that the better effect of
`prednisolone was limited to the descending and sigmoid
`segments of the colon, where a significant difference was
`found at 4 weeks (Figure 2). Three of 31 patients were
`in histological remission in the budesonide group after
`4 weeks vs. 6 of 36 patients in the prednisolone group
`(P Å 0.63). Eleven patients in the budesonide group had
`improved histopathologic scores compared with 22 in
`the prednisolone group (P Å 0.065).
`
`Figure 2. Mean (A) colonoscopic and (B) histopathologic activity
`scores in each of the five colorectal segments at entry and after 4
`weeks of treatment with either budesonide (Bud) or prednisolone
`(Pred) expressed as D values. Colonoscopy scored between 0 and 3,
`and histopathology scored between 1 and 5.
`
`There was no significant difference between the two
`treatment groups with respect to change in endoscopic
`score when stratification was made for smoking habits
`(nonsmoker, ex-smoker, or current smoker) (P Å 0.15).
`On the other hand, endoscopic improvement was sig-
`nificantly greater (P õ 0.01) for smokers than for non-
`smokers and for ex-smokers, regardless of treatment (Ta-
`ble 4). Both treatment groups improved in terms of
`bowel symptoms during the course of the study. How-
`ever, there were no significant differences between the
`two treatment groups at any time point with regard to
`number of bowel movements and mucus discharges with
`or without blood.
`
`Safety
`
`No changes in blood pressure were detected in
`the two groups, but weight gain at the final follow-up
`was significantly greater in the prednisolone group (P Å
`0.042). There were no differences in blood chemistry and
`hematology parameters except for a slight but significant
`(P Å 0.017) elevation of the leukocyte count in the
`prednisolone group after 2 weeks. A significant decrease
`in platelet count and orosomucoid levels was also ob-
`
`Table 4. Effect of Smoking Habits on Endoscopic Score
`After 4 Weeks of Treatment
`
`Changes in mean endoscopic scores
`from entry
`
`Prednisolone
`Budesonide
`00.9 (n Å 20)
`00.5 (n Å 16)
`Nonsmokers
`00.9 (n Å 10)
`00.4 (n Å 8)
`Ex-smokers
`01.8 (n Å 6)
`01.9 (n Å 6)
`Current smokersa
`aPõ 0.01 compared with nonsmokers and ex-smokers.
`
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`ORAL BUDESONIDE IN ULCERATIVE COLITIS 1717
`
`treated patients showed a greater tendency for adverse
`events from the central and peripheral nervous system
`(3% vs. 13%).
`
`Discussion
`This is the first controlled pilot study of UC in
`which oral budesonide has been compared with predniso-
`lone. The overall endoscopic evaluation did not yield
`any statistically significant differences between the two
`regimens, although in the analysis of the effect on endo-
`scopic score in the separate colorectal segments, predniso-
`lone was superior in the sigmoid colon after 4 weeks
`of treatment. Thus, budesonide seems to have an anti-
`inflammatory effect in most of the colon and in the rec-
`tum approaching the effect of prednisolone. The effect
`of budesonide seems to be mainly topical, as indicated
`by the lack of suppression of endogenous plasma cortisol
`levels.
`From the results of other trials,2 – 5 it was expected that
`budesonide capsules would have some, albeit limited,
`effect on plasma cortisol levels. The fact that budesonide
`capsules in the doses and the pharmaceutical formulation
`used in this trial did not affect plasma cortisol levels in
`this trial may be partly because of the high first-pass
`metabolism of the drug, but it is more likely because of
`an incomplete release of budesonide, particularly in the
`distal colon. The latter is supported by the fact that
`a 9-mg dose of budesonide in another pharmaceutical
`formulation with a faster drug-release profile suppressed
`basal plasma cortisol levels in the order of 40% in pa-
`tients with active Crohn’s disease.8,12 Further data are
`awaited from absorption and pharmacokinetic studies.
`Early trials of cortisone in the 1950s established the
`efficacy of corticosteroids in the treatment of active UC.9
`Prednisolone has since become the standard drug for
`moderate attacks of UC, administered in a dose of ap-
`proximately 40 mg daily for the first few weeks and then
`decreased as soon as the disease responds to treatment.
`This regimen is considered to give optimal response with
`minimal side effects. However, the dosage is dependent
`on therapeutic traditions, and intial doses may vary be-
`tween 30 and 60 mg in different countries. Side effects
`have been shown to be dose dependent.13
`In this study, treatment with prednisolone tended to
`be more efficacious than treatment with budesonide.
`There may be several reasons for this outcome. One expla-
`nation may be that the budesonide dose was too low and
`did not reach the distal colon in sufficient concentrations
`or that the release was too slow, considering that the
`passage of feces through the distal colon is a fairly rapid
`process in the active phase of UC.14 After defecation,
`even in patients with diarrhea, the distal colon is likely
`
`Figure 4. Plasma cortisol levels during treatment with oral budeson-
`) or prednisolone (–rr–rr–) for active UC. All patients
`ide (
`treated and last-value-extended principle. Values are expressed as
`mean { SEM.
`
`served in the prednisolone group. Other clinical chemis-
`try, including liver function tests, did not show any clini-
`cally relevant changes attributed to the treatment.
`Mean plasma cortisol levels were unchanged in the
`budesonide group during the entire study period,
`whereas the levels in the prednisolone group were sig-
`nificantly depressed after 2 and 4 weeks of treatment
`(Figure 4). No patient in the budesonide group had a
`plasma cortisol level less than the lower reference limit
`of 150 nmol/L at any time during the study vs. 25 of
`33 patients in the prednisolone group after 2 weeks (P õ
`0.001), 21 of 34 patients after 4 weeks (P õ 0.001), and
`6 of 34 patients after 9 weeks (P Å 0.047).
`Adverse events were generally mild in both groups
`and caused discontinuation of the treatment in 3 patients.
`One patient in the budesonide group discontinued treat-
`ment because of vomiting in combination with deteriora-
`tion of disease, and 1 patient discontinued because of a
`rash. One patient treated with prednisolone discontinued
`treatment because of insomnia (Table 3).
`Another patient in the budesonide group with primary
`sclerosing cholangitis had moderately elevated alkaline
`phosphatase values at entry and had a significant increase
`during the study. As the colitis symptoms subsided, the
`levels decreased, and any casual relationship with the
`study drug was considered unlikely. One patient in the
`prednisolone group developed a Cushing-like syndrome.
`One patient in the budesonide group developed pneumo-
`nia, but the study drug was continued unaltered, and
`the patient improved after being treated with antibiotics.
`One patient in the prednisolone group developed severe
`edema of the legs requiring hospitalization and treatment
`with diuretics. In general, the patients in the budesonide
`group had a higher incidence of gastrointestinal tract
`adverse events (35% vs. 10%), whereas the prednisolone-
`
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`1718 LO¨ FBERG ET AL.
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`GASTROENTEROLOGY Vol. 110, No. 6
`
`to be largely empty of feces. Thus, one of the most
`inflamed parts of the colon in UC may only be exposed
`to the drug intermittently and only before defecation.
`Therefore, studies of the colonic absorption of budesonide
`in patients will be necessary to clarify how much of an
`administered dose of budesonide in the pharmaceutical
`formulation used in this study is in fact delivered and
`absorbed in different parts of the colon.
`Both groups improved significantly with respect to
`bowel symptoms. The systemic GCS effects of predniso-
`lone may explain the gain in weight in this group.
`It is noteworthy that smokers had a significantly better
`improvement of the mean endoscopic score than nonsmok-
`ers or ex-smokers. This observation is in accordance with a
`recent report of the beneficial effect of transdermal nicotine
`administration.15 However, this result may have occurred
`by chance alone, given that it was based on a subgroup
`analysis and was not a previously specified hypothesis. Only
`a limited systemic impact of prednisolone was observed
`when changes in clinical chemistry and hematology were
`assessed. Three patients, all in the prednisolone group,
`experienced side effects that were clearly GCS related. In
`contrast to a recent study8 in which efforts were made to
`distinguish possible differences in GCS-related side effects
`between budesonide- and prednisolone-treated patients, no
`such assessment was specifically aimed at in this study.
`This may have caused an underestimation of possible GCS-
`related side effects.
`Evaluation of other topical steroids for treatment in
`extensive UC, such as fluticasone propionate,16 have
`shown significantly inferior results when compared with
`standard prednisolone treatment. However, there are cer-
`tain fundamental problems when treating extensive UC
`with topical formulations, including factors such as pH
`and local colonic transit time, which both seem to change
`when the disease activity is decreasing.14
`In conclusion, this study has shown that the topically
`active GCS budesonide, administered in an oral con-
`trolled-release formulation at an initial dose of 10 mg/
`day, seems to give an overall treatment result in patients
`with active UC, approaching that of 40 mg/day of pred-
`nisolone with gradual tapering but without any suppres-
`sion of morning plasma cortisol levels. Because endo-
`scopic and histological improvement in the distal colon
`was in favor of prednisolone, this could indicate a subop-
`timal release of budesonide in this region. The finding
`made in this exploratory study merits further evaluation,
`and new studies using improved formulations of bude-
`sonide are now in progress.
`References
`1. Brattsand R. Overview of the newer glucocorticoid preparations
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`
`Received June 16, 1995. Accepted January 5, 1996.
`Address requests for reprints to: Robert Lo¨fberg, M.D., Unit of
`Gastroenterology, Karolinska Institute, Huddinge University Hospital,
`S-141 86 Huddinge, Sweden. Fax: (46) 8-608-2241.
`Supported by Astra Draco AB, Lund, Sweden.
`Presented in part as a poster at the World Congresses of Gastroen-
`terology in Los Angeles, California, on October 2–7, 1994.
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