Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome.

BACKGROUND: The low-FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction; however, guidelines recommend that high-FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long-term effectiveness of the low-FODMAP diet following FODMAP reintroduction in IBS patients. METHODS: Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian-led low-FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food-related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual). KEY RESULTS: Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at long-term follow-up. At long-term follow-up, 84 (82%) patients continued an 'adapted FODMAP' diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with 19 (18%) of patients following a 'habitual' diet (29.4, SD 22.9 g/d, P=.039). Nutritional adequacy was not compromised for either group. The 'adapted FODMAP' group reported the diet cost significantly more than the 'habitual' group (P<.001) and affected social eating (P<.01) but there was no effect on food-related QOL. Healthcare utilization was similar between both groups. CONCLUSION AND INFERENCES: Low-FODMAP education is effective for long-term IBS management, enables a nutritionally adequate diet, and is broadly acceptable to patients.

Utilisation of anti-TNF levels in a UK tertiary IBD centre.

OBJECTIVE: To ascertain how anti-tumour necrosis factor (TNF) drug and anti-drug antibody levels testing is used in a 'real-world' setting to optimise inflammatory bowel disease (IBD) treatment. DESIGN: Retrospective cohort study of prospectively collected patient data. SETTING: Tertiary IBD centre in London, UK. PATIENTS: All patients at Guy's and St Thomas' Hospitals on anti-TNF who had levels measured between the start of testing in 2012 and October 2014. INTERVENTIONS: Anti-TNF drug and anti-drug antibody levels as part of routine monitoring. MAIN OUTCOME MEASURES: Indication for measuring levels and changes in management made as a result of the levels. RESULTS: 330 infliximab levels were carried out in 199 patients and 143 adalimumab levels were carried out in 103 patients. Levels were primarily done in those with evidence of loss of response; 37% of infliximab levels and 52% of adalimumab levels. Levels resulted in a change in management in 26% of patients in infliximab group and 25% of patients in adalimumab group; however, this was greater in those with loss of response, 62% and 61% respectively. Anti-drug antibodies were detected in 7% of patients. CONCLUSIONS: Our early experience has demonstrated that measuring anti-TNF drug and anti-drug antibody levels can be useful in the optimisation of IBD management. In an increasing number of patients, particularly those with evidence of loss of response, it allows early decisions to be made regarding changing therapy. It also offers the potential for significant cost-saving by preventing pointless dose escalation in the context of therapeutic levels or when high-level anti-drug antibodies are present.

Infliximab and adalimumab drug levels in Crohn's disease: contrasting associations with disease activity and influencing factors.

BACKGROUND: Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. AIMS: To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. METHODS: We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey-Bradshaw index, C-reactive protein and faecal calprotectin. 6-tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines. RESULTS: A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (P<.0001) with corresponding thresholds identified on ROC analysis of 1.5, 3.4 and 5.7 µg/mL. Adalimumab levels were similar between active disease and remission regardless of the endpoint assessed. Modelling identified that higher infliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels. CONCLUSIONS: Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels.

Clinical effectiveness and economic costs of group versus one-to-one education for short-chain fermentable carbohydrate restriction (low FODMAP diet) in the management of irritable bowel syndrome.

BACKGROUND: Restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is an effective dietary treatment for irritable bowel syndrome (IBS). Patient dietary education is essential but labour intensive. Group FODMAP education may alleviate this somewhat but has not previously been investigated. The present study aimed to investigate the clinical effectiveness of low FODMAP group education in patients with IBS and to explore the cost of a group pathway. METHODS: Patients with IBS (n = 364) were assessed for their suitability to attend dietitian-led group education or traditional one-to-one education in a novel group pathway. Clinical effectiveness (global symptom question, symptom prevalence, stool output) were compared at baseline and follow-up using the chi-squared test. The costs of the novel group pathway were assessed using a decision model. RESULTS: The global symptom question indicated more patients were satisfied with their symptoms following dietary advice, in both group education [baseline 48/263 (18%) versus follow-up 142/263 (54%), P < 0.001] and one-to-one education [baseline 5/101 (5%) versus follow-up 61/101 (60%), P < 0.001], with no difference between group and one-to-one education at follow-up (P = 0.271). Overall, there was a significant decrease in symptom severity from baseline to follow-up (P < 0.001 for both groups) but no difference in symptom response between group and one-to-one education. The cost for the group education pathway for all 364 patients was £31 713.36. CONCLUSIONS: The present study shows that dietitian-led FODMAP group education is clinically effective and the costs associated with a FODMAP group pathway are worthy of further consideration for routine clinical care.

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Reassessment of Crohn's disease treated with at least 12†months of anti-TNF therapy: how likely is treatment withdrawal?

OBJECTIVE: To assess methods of disease reassessment and rates of treatment withdrawal in patients with Crohn's disease (CD) treated with biologics and to report retrospective risk stratification for treatment withdrawal as suggested by the STORI trial in the context of this cohort. DESIGN: A retrospective observational cohort study of all patients with CD treated with antitumour necrosis factor (anti-TNF) therapy for >12 months in 2011. SETTING: Tertiary care. PATIENTS: Patients with CD treated with anti-TNF therapy. MAIN OUTCOME MEASURES: Method and outcome of reassessment and whether patient was withdrawn from therapy; also, whether patients met low-risk criteria for withdrawal as identified by the STORI trial, and outcome of those meeting low-risk criteria. RESULTS: 73 patients (infliximab n=48, adalimumab n=25) underwent disease reassessment. Nine patients were deemed to have achieved remission and were withdrawn from treatment: 6 (67%) maintained remission at 12 months, three patients relapsed and were successfully retreated. 52 patients had sufficient data available for STORI criteria to be applied retrospectively. 37% (19/52) fulfilled low-risk criteria for withdrawal-of these, 26% (5/19) were withdrawn from anti-TNF therapy and three had sustained clinical remission at 1 year. Reasons for non-withdrawal included ongoing endoscopic activity (n=8), radiological activity (n=2) and clinical concern due to previous disease behaviour (n=4). CONCLUSIONS: Relatively few patients were deemed in sufficient depth of remission to warrant a trial of withdrawal of anti-TNF therapy. Many patients were not withdrawn, despite meeting STORI low-risk criteria, due to ongoing disease activity highlighting the limitations of applying such criteria in a 'real world' setting.

Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

Mechanism of allopurinol induced TPMT inhibition.

Up to 1/5 of patients with wildtype thiopurine-S-methyltransferase (TPMT) activity prescribed azathioprine (AZA) or mercaptopurine (MP) demonstrate a skewed drug metabolism in which MP is preferentially methylated to yield methylmercaptopurine (MeMP). This is known as thiopurine hypermethylation and is associated with drug toxicity and treatment non-response. Co-prescription of allopurinol with low dose AZA/MP (25-33%) circumvents this phenotype and leads to a dramatic reduction in methylated metabolites; however, the biochemical mechanism remains unclear. Using intact and lysate red cell models we propose a novel pathway of allopurinol mediated TPMT inhibition, through the production of thioxanthine (TX, 2-hydroxymercaptopurine). In red blood cells pre-incubated with 250 µM MP for 2h prior to the addition of 250 µM TX or an equivalent volume of Earle's balanced salt solution, there was a significant reduction in the concentration of MeMP detected at 4h and 6h in cells exposed to TX (4 h, 1.68, p=0.0005, t-test). TX acts as a direct TPMT inhibitor with an apparent Ki of 0.329 mM. In addition we have confirmed that the mechanism is relevant to in vivo metabolism by demonstrating raised urinary TX levels in patients receiving combination therapy. We conclude that the formation of TX in patients receiving combination therapy with AZA/MP and allopurinol, likely explains the significant reduction of methylated metabolites due to direct TPMT inhibition.

Setting priorities for comparative effectiveness research in inflammatory bowel disease: results of an international provider survey, expert RAND panel, and patient focus groups.

BACKGROUND: Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). METHODS: Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. RESULTS: Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. CONCLUSIONS: We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies.

Factors associated with nonadherence to thiopurines in adolescent and adult patients with inflammatory bowel disease.

OBJECTIVES: We hypothesised that nonadherence to thiopurines is more common in adolescents than in adults with inflammatory bowel disease. METHODS: We sought factors associated with thiopurine nonadherence defined by thiopurine metabolite levels. RESULTS: Multivariate logistic regression confirmed that adolescents (odds ratio [OR] 4.6 [95% confidence interval [CI] 1.9-11.5]; P < 0.01) compared with adults, patients with Crohn disease (OR 3.3 [CI 1.1-10.5] P = 0.04) compared with ulcerative colitis, and patients living in more socially deprived areas (OR 1.03 [CI 1.0-1.1] P = 0.02) were more likely to be nonadherent to thiopurines. CONCLUSIONS: Adolescents are more frequently nonadherent than adults: prospective studies are required to determine the reasons for nonadherence in adolescents.

Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome.

BACKGROUND: Emerging evidence indicates that the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may result in symptoms in some patients with irritable bowel syndrome (IBS). The present study aimed to determine whether a low FODMAP diet is effective for symptom control in patients with IBS and to compare its effects with those of standard dietary advice based on the UK National Institute for Health and Clinical Excellence (NICE) guidelines. METHODS: Consecutive patients with IBS who attended a follow-up dietetic outpatient visit for dietary management of their symptoms were included. Questionnaires were completed for patients who received standard (n = 39) or low FODMAP dietary advice (n = 43). Data were recorded on symptom change and comparisons were made between groups. RESULTS: In total, more patients in the low FODMAP group reported satisfaction with their symptom response (76%) compared to the standard group (54%, P = 0.038). Composite symptom score data showed better overall symptom response in the low FODMAP group (86%) compared to the standard group (49%, P < 0.001). Significantly more patients in the low FODMAP group compared to the standard group reported improvements in bloating (low FODMAP 82% versus standard 49%, P = 0.002), abdominal pain (low FODMAP 85% versus standard 61%, P = 0.023) and flatulence (low FODMAP 87% versus standard 50%, P = 0.001). CONCLUSIONS: A low FODMAP diet appears to be more effective than standard dietary advice for symptom control in IBS.

Poster presentations at medical conferences: an effective way of disseminating research?

This study aimed to ascertain the value of posters at medical meetings to presenters and delegates. The usefulness of posters to presenters at national and international meetings was evaluated by assessing the numbers of delegates visiting them and the reasons why they visited. Memorability of selected posters was assessed and factors influencing their appeal to expert delegates identified. At both the national and international meetings, very few delegates (< 5%) visited posters. Only a minority read them and fewer asked useful questions. Recall of content was so poor that it prevented identification of factors improving their memorability. Factors increasing posters' visual appeal included their scientific content, pictures/graphs and limited use of words. Few delegates visit posters and those doing so recall little of their content. To engage their audience, researchers should design visually appealing posters by presenting high quality data in pictures or graphs without an excess of words.

Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease.

BACKGROUND: Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine-related malignancy. AIM: To review the literature, exploring how immunosuppression, thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts. METHODS: Search terms included 'malignancy' 'cancer' 'azathioprine' 'mercaptopurine' 'tioguanine (thioguanine)' 'thiopurine' and 'inflammatory bowel disease' 'Crohn's disease' 'ulcerative colitis'. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected. RESULTS: Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine-related malignancies have been reported. However, studies suggest a relative risk of 4-5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300-1400 years of thiopurine treatment). CONCLUSIONS: Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients' risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide.

Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon.

BACKGROUND: Functional gut symptoms are induced by inclusion and reduced by dietary restriction of poorly absorbed short-chain carbohydrates (FODMAPs), but the mechanisms of action remain untested. AIMS: To determine the effect of dietary FODMAPs on the content of water and fermentable substrates of ileal effluent. METHODS: Twelve ileostomates without evidence of small intestinal disease undertook two 4-day dietary periods, comprising diets differing only in FODMAP content in a randomized, cross-over, single-blinded intervention study. Daytime (14 h) ileal effluent was collected on day four of each diet. Patients rated effluent volume and consistency on a 10-cm visual analogue scale. The FODMAP content of the diet and effluent was measured. RESULTS: Ingested FODMAPs of 32% (range 6-73%) was recovered in the high FODMAP diet effluent. Effluent collection weight increased by a mean of 22% (95% CI, 5-39), water content by 20% (2-38%) and dry weight by 24% (4-43%) with the high compared to low FODMAP diet arm. Output increased by 95 (28-161) mL. Volunteers perceived effluent consistency was thicker (95% CI, 0.6-1.9) with the low FODMAP diet than with the high FODMAP diet (3.5-6.1; P = 0.006). CONCLUSIONS: These data support the hypothetical mechanism; FODMAPs increase delivery of water and fermentable substrates to the proximal colon.

Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders.

BACKGROUND: Fructose malabsorption, lactose malabsorption and an early rise in breath hydrogen after lactulose (ERBHAL) may play roles in induction of symptoms in gastrointestinal conditions. AIM: To compare prevalence and interactions of fructose malabsorption, lactose malabsorption and ERBHAL among healthy subjects and those with chronic intestinal disorders using consistent breath hydrogen testing methodologies. METHODS: Consecutive series of Caucasian patients with Crohn's disease (n = 91), ulcerative colitis (56), functional gastrointestinal disorders (FGID) (201), coeliac disease (136) and 71 healthy volunteers underwent breath hydrogen testing using lactulose, fructose and lactose. RESULTS: Early rise in breath hydrogen after lactulose occurred more commonly in healthy controls (39%) than in Crohn's disease (20%) and untreated coeliac disease (14%; P < 0.008), but not FGID (27%), ulcerative colitis (26%) or treated coeliac disease (29%). Fructose malabsorption was more frequent in Crohn's disease (61%) than other groups (33-44%, P < 0.05). Lactose malabsorption was most common in Crohn's disease (42%) and ulcerative colitis (40%) and uncommon (10%) in 79 patients with newly diagnosed coeliac disease. In Crohn's disease, concurrent Fructose malabsorption and lactose malabsorption was most common (29%), and the association of fructose malabsorption with ERBHAL seen overall (62%) was not observed (36%, P < 0.0001). CONCLUSIONS: Carbohydrate malabsorption and ERBHAL are normal physiological phenomena. The abnormal patterns observed in Crohn's disease may have pathogenic importance.

Quality, clinical influence and tolerance of computed tomography enteroclysis in patients with suspected small bowel disease.

BACKGROUND: Computed tomography enteroclysis (CTE) may be superior to other small bowel imaging techniques, detecting subtle mucosal lesions and extraluminal pathology. This study aimed to define the technical success, clinical influence and tolerance of CTE in patients with suspected small bowel disease. METHODS: CTE scans of 42 consecutive patients (aged 21-78 years, 12 men) were reviewed by a single radiologist for technical adequacy and diagnosis. A panel of gastroenterologists reviewed clinical information. At a telephone interview, tolerance of CTE was graded numerically from 1 (unbearable) to 10 (excellent) and descriptively as unbearable, fair, good or excellent. RESULTS: Good or optimal distension of small bowel was achieved in 98%. The entire small bowel was imaged in 88%. Eighteen patients had a normal small bowel, whereas 12 (29%) had active small bowel Crohn disease, 4 intussusception, 3 small bowel diverticula and 7 having other diagnoses. Mesenteric lymphadenopathy was evident in 11 and fat stranding in 5. CTE resulted in a new or altered diagnosis in 13 (31%) patients and identified more extensive Crohn disease in a further 8 (19%). A change in management plan was instituted in 18 (43%) patients, with subsequent clinically significant improvement in 12. 33 (85%) described the procedure as 'fair' or 'unbearable' rather than 'good' or 'excellent'. The median tolerance score was 3 out of 10. CONCLUSION: CTE provided high-quality images in nearly all patients and had an effect on diagnosis, management or outcome in most, but was not well tolerated.

Management of distal ulcerative colitis: frequently asked questions analysis.

The majority of patients with ulcerative colitis have disease involving only the distal colon. Although 5-aminosalicylic acid (5-ASA, mesalazine) and corticosteroids remain the important drugs used in the management of distal colitis and proctitis, recent expansion of delivery options of 5-ASA and high level evidence regarding efficacy have led to a shift in treatment strategies. The availability of 5-ASA in enema, foam and suppository formulations has enabled optimization of delivery of 5-ASA to the affected mucosa. Such therapy has superior efficacy and fewer adverse effects compared with those of topical corticosteroids. Furthermore, rectal delivery is effective in the maintenance of remission. Consequently, new guidelines for the management of distal colitis have focussed more on rectal delivery and on optimizing 5-ASA dosage than previously. However, corticosteroids remain an important remission-inducing agent, and immune-modulating drugs play a clear role in prevention of relapse and in managing chronically active disease. The changes in guidelines have raised several management questions, many of which are addressed in this review.

Review article: appropriate use of corticosteroids in Crohn's disease.

BACKGROUND: Corticosteroids are a well-established treatment for active Crohn's disease and have been widely used for decades. It has become apparent, however, that a proportion of patients either fails to respond to corticosteroids or is unable to withdraw from them without relapsing. Furthermore, their use is associated with a range of side effects, such that long-term treatment carries unacceptable risk. AIM: To review the evidence regarding the appropriate use of corticosteroids in Crohn's disease, along with their side effects, safety and alternatives. METHODS: To collect relevant articles, a PubMed search was performed from 1966 to November 2006 using the terms 'steroid', 'corticosteroid', 'glucocorticoid', 'prednisolone', 'prednisone', 'methylprednisolone', 'hydrocortisone', 'dexamethasone' and 'budesonide' in combination with 'Crohn(s) disease'. Relevant articles were reviewed, as were their reference lists to identify further articles. RESULTS: When used correctly, corticosteroids are a highly effective, well tolerated, cheap and generally safe treatment for active Crohn' disease. Nevertheless, approximately 50% of recipients will either fail to respond (steroid-resistant) or will be steroid dependent at 1 year. Newer alternatives to corticosteroids are not, however, without risk themselves and, moreover, are not necessarily available universally. CONCLUSIONS: Steroids are used widely to treat Crohn's disease, a situation that is unlikely to change in the near future. Accordingly, efforts should be made to ensure that they are used correctly and that their side effects are minimized. Reference is made to recently published guidelines and a simplified 'users guide' is presented.