Immunosuppression In Inflammatory Bowel Disease Research Articles

Safety of Biologic and Small Molecule Therapy for Inflammatory Bowel Disease Among Solid Organ Transplant Recipients: Systematic Review and Meta-Analysis.

Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients. Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy. Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported. Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.

COVID-19 in Children With Inflammatory Bowel Disease: A Systematic Review

Background: Considering the chronic immunosuppression in Inflammatory Bowel Disease (IBD) patients, it is necessary to evaluate the course of COVID-19 in these patients. Studies have shown various results in adult IBD patients. This study aimed to find out the course of this infection in pediatric IBD patients. Methods: This was a systematic review study according to the PRISMA 2020 guideline. International databases including Scopus, PubMed, and the Web of Science were searched with a combination of “COVID-19” AND “IBD” or synonyms until October 16, 2021. Studies that have reported the outcomes of COVID-19 infection in patients less than 19 years of age were selected. Name of author, country, study duration and type, IBD type and drugs, and COVID-19 outcomes were extracted. Results: From the initially retrieved 2215 articles, finally 16 articles were eligible. Data from 1040 pediatric IBD patients were reported. Twenty-four patients were hospitalized, 5 developed patients multisystem inflammatory syndrome in children, and others had a mild disease course and were outpatient. Steroid use, severe IBD activity, and comorbidities were shown to increase risk of hospitalization and disease severity. Conclusions: COVID-19 is a benign and self-limited disease in pediatric IBD patients. Comorbidities, steroid use, and severe IBD activity affect the outcomes.

Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.

Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn’s disease (CD) n = 214 and ulcerative colitis (UC) n = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; p = 0.012), concomitant diseases (AA vs. AG vs. GG; p = 0.015) and cutaneous manifestations (AA vs. AG/GG, p = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; p = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease (p = 0.020) and time-to-immunosuppression (p = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; p = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.

Immunosuppression in Rheumatologic and Auto-immune Disease.

Many rheumatologic diseases are thought to originate in dysregulation of the immune system; lupus nephritis, for example, involves humoral immunity, while autoinflammatory diseases such as familial Mediterranean fever are caused by defects in innate immunity. Of note, this dysregulation may involve both upregulation of immune system components and aspects of immunodeficiency. Treatment of rheumatologic diseases thus requires a familiarity with a variety of immunosuppressive medications and their effects on immune system function.In many rheumatologic conditions, due to an incompletely elucidated mechanism of disease, immunosuppression is relatively broad in contrast to agents used, for example, in treatment of transplant rejection. Multiple immunosuppressive drugs may also be used in succession or in combination. As such, an understanding of the mechanisms and targets of immunosuppressive drugs is essential to appreciating their utility and potential adverse effects. Because of the overlap between therapies used in rheumatologic as well as other inflammatory disorders, some of these medications are discussed in other disease processes (e.g., Immunosuppression for inflammatory bowel disease) or in greater detail in other chapters of this textbook (corticosteroids, mTOR inhibitors, antiproliferative agents).

The interplay of Clostridioides difficile infection and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

Immunosuppression for inflammatory bowel disease does not influence Epstein–Barr viral load in the short-term

Immunosuppression for inflammatory bowel disease does not influence Epstein–Barr viral load in the short-term

Immunosuppression for inflammatory bowel disease does not influence Epstein–Barr viral load in the short-term

IntroductionImmunomodulators and biologics are two of the main drugs used for the treatment of inflammatory bowel disease (IBD). Some of these agents have been associated with certain infections and lymphoproliferative disorders, including Epstein–Barr virus (EBV) infection. Our aim was to determine the influence of immunosuppression in the EBV viral load in patients with IBD. Materials and methodsWe prospectively included naïve patients with IBD who were starting immunosuppressive therapy in four IBD Units. All patients were assessed at baseline and four months after starting immunosuppression for clinical disease activity, biomarkers, EBV serology (IgM VCA, IgG VCA and IgG EBNA) and viral load. ResultsThirty-two patients were included. At baseline, all patients showed positive results for IgG VCA or IgG EBNA with undetectable EBV viral load. No patient showed detectable EBV viral load after starting the immunosuppressive therapy. ConclusionImmunosuppression did not influence on EBV viral load in the short-term in naïve IBD patients.

HucMSCs Attenuate IBD through Releasing miR148b-5p to Inhibit the Expression of 15-lox-1 in Macrophages.

Mesenchymal stem cells (MSCs) exert powerful immunosuppression in inflammatory bowel disease (IBD). Macrophages are the dominant inflammatory cells in enteritis regulated via MSCs. However, the roles of macrophages in the process of MSCs attenuating IBD and the mechanisms of MSCs regulating macrophages are largely unknown. In this study, DSS- (dextran sulfate sodium salt-) induced IBD in macrophage-depleted models of CD11b-DTR mice was used to study the relationship between hucMSCs (human umbilical cord mesenchymal stromal cells) and macrophage. Body weights, disease activities, and pathological changes were documented to assess the therapeutic effects of hucMSCs. Furthermore, hucMSCs transfected with miR148b-5p mimics and miR148b-5p inhibitors were cocultured with LPS-induced RAW264.7 cells to investigate the role of miR148b-5p in hucMSC-regulated colitis. The outcome indicated that hucMSCs attenuated the IBD by downregulating 15-lox-1 expression in macrophages. Further findings pointed out that hucMSCs transfected with miR148b-5p mimics could be elevated to promote the tissue repair and inhibit the expression of 15-lox-1 but failed to perform the function of easing enteritis when treated with miR148b-5p inhibitors. In conclusions, we propose that hucMSCs attenuate IBD by releasing miR148b-5p to inhibit the expression of 15-lox-1 in macrophages.

Determining Health Utilities for Immunosuppression in Pediatric Inflammatory Bowel Disease

Background and Hypothesis: Inflammatory Bowel Disease is a significant cause of gastrointestinal pathology in children and adolescents, with increasing incidence. The medications used to control this disease have an overall low risk of detrimental side effects, but when they occur can be serious or life-threatening. The most important side effects of immunosuppression in IBD are infection and malignancy, but little is known about how these risks affect patients’ and their families’ decisions about medication use. Clinical utilities are a standard methodology used to assign risk to various hypothetical health states. We hypothesized that lower health utility scores would be assigned to scenarios related to cancer than to infection, even if the risks or severity were similar. 
 Experimental Design or Project Methods: This study determines the clinical utility of immunosuppression and cancer / infection risk in children with inflammatory bowel disease using the standard gamble technique. The standard gamble technique measures individual preferences for many different therapeutic modalities, under uncertain results. The study will look at the health utilities of at least 50 families at Riley hospital for Children and IU North, with at least 25 patients with ulcerative colitis and 25 patients with Crohn’s disease. In addition to the perfect health and death, we propose to utilize six different hypothetical health states during this study: (1) untreated IBD, (2) on a medication with no side effects, (3) on a medication with risk of a treatable infection, (4) on a medication with risk of an untreatable infection, (5) on a medication with risk of a treatable cancer, (6) and on a medication with risk of an untreatable cancer. We will also gather subject demographics, family education, family income, and perform an assessment of numeracy. These variables will then be used in a regression model to assess the effect of these confounders. 
 Results: We have not yet enrolled subjects, but now that the tool and Standard Gamble design are complete, we expect to rapidly accrue enrollment over the next two weeks and will update results at that time. 
 Conclusion and Potential Impact: Health utility data in pediatric IBD are quite scarce, with room for further research. It is crucial to understand the health utilities in individuals with inflammatory bowel disease (IBD), specifically in pediatric patients. This allows for cost-utility analysis to play a role in determining effectiveness for a wide variety of treatment modalities. It is also important when discussing treatment options with families when the risk of infection or cancer are present. Knowledge gained from this study may help us design interventions that focus on educating families about the nature and magnitude of these important risks in immunosuppressive therapy.

P753. Immunosuppression for inflammatory bowel disease does not affect Epstein–Barr viral load in the short-term: preliminary results

P753. Immunosuppression for inflammatory bowel disease does not affect Epstein–Barr viral load in the short-term: preliminary results

Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases

Infections are an important concern in patients using immunosuppressive therapy for their inflammatory bowel disease (IBD). Diabetes affects nearly 10% of Americans. Whether it confers an additional risk with immunosuppression in IBD has not been examined previously. To examine the association between diabetes and infections with immunomodulator use in IBD METHODS: Using a validated, multi-institutional IBD cohort, we identified all patients who received at least one prescription for immunomodulators (thiopurines, methotrexate). Our primary outcome was infection within 1year of the prescription of the immunomodulator. Multivariable logistic regression adjusting for relevant confounders was used to estimate the independent association with diabetes. Our study included 2766 patients receiving at least one prescription for immunomodulators among whom 210 (8%) developed an infection within 1year. Patients who developed an infection were likely to be older, have more comorbidities, more likely to have received a prescription for steroids but similar in initiation of anti-TNF therapy within that year. Only 8% of those without an infection had diabetes compared to 19% of those who developed an infection within 1year [odds ratio (OR) 2.74, 95% confidence interval (CI) 1.88-3.98, P<0.001]. On multivariate analysis, diabetes was independently associated with a nearly two-fold increase in risk of infections (OR: 1.80, 95% CI: 1.20-2.68). There was no increase in risk of infections with addition of anti-TNF therapy (OR: 1.14, 95% CI: 0.80-1.63). Diabetes is an independent risk factor for infection in IBD patients using immunomodulator therapy.

P190 Low muscle mass in inflammatory bowel disease (IBD): common and predictive of functional sarcopenia and osteopenia

polymorphous angiocentric and angiodestructive infiltrate. LYG affects the lungs predominantly. The digestive tract is rarely involved. Patients with a primary or secondary immunodeficiency are at increased risk for LYG. We report a case of LYG in a patient with Crohn’s disease (CD). This description also identifies an EBV-driven B-cell lymphoma in a patient following methotrexate (MTX) immunosuppression for inflammatory bowel disease (IBD). We have proceeded to an extensive review of the literature and to the best of our knowledge no other cases of Lung-free LYG have been described in patient CD. Methods: 40 years old female. Diagnosed with Crohn disease when she was 20 years old, she was an estenotic colonic she needed right hemicolectomy and then she also needed transverse colectomy because of a new stenosis. Since then, she followed MTX treatment. She came for consult in July 2012 with malaise, weight loss, severe malnutrition, abdominal pain, inflammation in midline abdomen. A CT scan was performed: a subcutaneous collection was seen, and ileosigmoidy stenosis and bowel stenosis. Surgery was performed, ileosigmoid resection and protective ileostomy. There were no immediate complications after the procedure. She was admitted to the hospital again because of malaise, evening fever, pain in left hypochondrium, and dehydration. Pathology examination results were obtained, with the diagnosis of lymphomatoid granulomatosis. The Hematology Department was consulted and Rituximab treatment was initiated (4 cycles). A new colon biopsy was obtained by colonoscopy and refractoriness was shown. Treatment with R-CHOPx6 was prescribed, obtaining parcial remission. Salvage therapy (R-ESHAPx2) was administrated, following autologous bone marrow transplantation. Results: Management of the disease was extremely challenging because of the overlapping of symptoms between Crohn’s disease and Lymphomatoid Granulomatosis. Because it is a very rare condition, we needed to consult a renowned center in pathology. No lung affection has been shown during the development of the disease. Conclusions: Immunosuppression produced by Crohn’s disease treatment creates risks that must be assumed by patients and doctors that treat them. Complex clinical characteristics and with no response to conventional treatments must make us think about associated entities. Biologic treatments and more specific drugs could reduce the incidence of these serious diseases.

Two rare cases of Epstein–Barr virus‐associated lymphoproliferative disorders in inflammatory bowel disease patients on thiopurines and other immunosuppressive medications

The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy.

Immunosuppression in inflammatory bowel disease

Current treatment approaches favor the early introduction of immunomodulators and/or antitumor necrosis factor (TNF) agents. There is now strong evidence showing that combination therapy appears to be more effective than monotherapy in both ulcerative colitis and Crohn's disease. However, there are concerns associated with this strategy, and eventually the following questions will emerge when discussing therapeutic options with our patients: is it safe to maintain these therapies for the long-term?; how long should we maintain therapy?; and if we decide to stop or de-escalate therapy, what strategy should we use? During the past year new evidence regarding safety of long-term therapy with anti-TNF and immunomodulators, and predictors of relapse following therapy discontinuation have become available. In this review we aim to discuss some of the safety concerns related to the use of immunosuppressive drugs used in inflammatory bowel disease, as well as the possible strategy for de-escalation or discontinuation therapy. Eventually, choosing to stop either the anti-TNF or the immunomodulator is a case-by-case decision based on the estimated risk-benefit ratio. In addition to the identified predictors of relapse after therapy discontinuation, other considerations such as long-term safety, cost, and natural history of the disease must be brought into this discussion.

Severe immunosuppression in inflammatory bowel disease: opening the floodgates to opportunists?

Dear editor: Ulcerative colitis is a primarily non-infectious, chronic inflammatory bowel disease that typically affects the rectum and may involve the whole colon in an uninterrupted pattern. The disease has a high impact on the patients' health-related quality of life and is prone to repetitive hospitalisation. Therapeutic options primarily include lifestyle alterations, medical management and surgical interventions. Medical as well as surgical therapy may be associated with lifethreatening complications, which may require intensive care unit (ICU) admission. Here, we report on a female patient suffering from ulcerative colitis, whose medical therapy was complicated by toxic megacolon, and later on pulmonary aspergillosis and disseminated herpes zoster. A 55-year old woman with ulcerative colitis suffered from purulent haemorrhagic diarrhoea and weight loss of 9 kg within 2 weeks and was treated in a community general hospital for 6 weeks. Azathioprine (2.5 mg kg d p.o.) was administered for a total of 15 days and had been discontinued due to severe leukopenia. At that time, the patient had a high erythrocyte thiopurine methyl thiopurine methyltransferase (TPMT) activity (38 nmol h− gHb−; normal >23, intermediate 10–23, low <10 nmol h− gHb−), which represents the detoxifyfing enzyme for azathioprine. In addition, TPMT genotyping was performed and confirmed the absence of clinically relevant enzyme polymorphisms. Furthermore, toxic 6-thioguanine nucleotides (6-TGN) were undetectable in the patient's blood. Persistent bowel inflammation was treated with high doses of topical and systemic corticosteroids (prednisolone up to 2 mg kg− per day) and intravenous cyclosporine (3 mg kg− as continuous infusion over 24 h) in combination with antimicrobial therapy. Cyclosporine was discontinued after 6 days as leukopenia deteriorated, and subsequent immunomodulatory therapy consisted of mesalazine and regressive doses of prednisolone. At transferal to our university hospital, the patient presented the full clinical picture of toxic megacolon, which required emergency subtotal colectomy, blind closure of the rectum and percutaneous ileostomy. Following surgery, the patient was transferred to the intermediate care unit and treated with antimicrobial therapy (cefuroxime and metronidazole) and moderate doses of corticosteroids (prednisolone 1 mg kg per day). On postoperative day 3, she developed acute cholecystitis, which required urgent cholecystectomy and escalation of antimicrobial therapy (meropenem and vancomycin). Throughout the early clinical course, the patient remained leukopenic with white blood cell counts between 950 and 2,840 cells per microliter. Fractional lymphocyte count persisted below 10%. Filgrastim treatment (recombinant-methionyl human granulocyte colony-stimulating factor; r-metHuG-CSF; Christian Ertmer and Wolf A. Mardin equally contributed to this work.

Immunosuppression in inflammatory bowel disease: traditional, biological or both?

To focus on the emerging clinical evidence for the use of traditional immunosuppressives and biologicals in the treatment of inflammatory bowel disease. Evidence published this year indicates that in Crohn's disease the early use of combined infliximab and purine analogues before the introduction of steroid therapy induces faster steroid-free remission and improves mucosal healing. We have also learned that, in patients with Crohn's disease who are naïve to traditional immunosuppressive therapy, combined infliximab and azathioprine improves clinical and mucosal healing outcomes at 6 months. On the contrary, in patients already exposed to traditional immunosuppressives prior to starting infliximab, withdrawal of azathioprine or methotrexate after 6 months of combined scheduled infliximab maintenance with these agents does not affect outcomes after 2 years of continued infliximab therapy. Finally, several important studies on the safety of immunosuppressives including anti-tumour necrosis factor agents have been published. The cumulative body of evidence suggests that combined immunosuppressive therapy in patients with inflammatory bowel disease increases toxicity. Treatment paradigms for traditional immunosuppressives and biologicals in inflammatory bowel disease are evolving, and the choice of therapy becomes highly dependent on the drugs previously used and disease severity.

S1095 Withdrawal of Immunosuppression in Inflammatory Bowel Disease Treated with Infliximab Maintenance Therapy

S1095 Withdrawal of Immunosuppression in Inflammatory Bowel Disease Treated with Infliximab Maintenance Therapy

Perineal Hernia After Proctectomy: Prevalence, Risks, and Management

Perineal hernias are infrequent complications of abdominoperineal operations with estimated historic prevalences (from the era where the perineal wound was left open) ranging from 0.6 to 7 percent. The purpose of this study was to identify the modern prevalence of postoperative perineal hernias, factors that may contribute to their development, and examine the methods of repair. The Mayo Clinic patient database (1990-2000) was interrogated for the following data identifiers: incisional hernia, perineal hernia, abdominoperineal resection, proctocolectomy, and partial or total pelvic exenteration. All surviving patients were followed up to December 2005. The retrieved patient data was retrospectively analyzed. Of a total of 3,761 patients who underwent abdominoperineal resection (including nonrestorative proctocolectomy and pelvic exenteration) during the study period, 8 developed a perineal hernia (5 females). The median age at hernia presentation was 76 (range, 69-84) years, representing a median interval of 22 (range, 1-60) months from the original operation. All were smokers (> or =15 pack years) and five had received chemoradiotherapy for their original diagnosis. The commonest prevalence was found in patients who had undergone abdominoperineal resection (5/1,266) or pelvic exenteration (2/1,334). Only 1 of 1,161 patients developed a perineal hernia after proctocolectomy despite most being on perioperative immunosuppression for inflammatory bowel disease. Abdominal exploration and repair was performed in four patients whereas four underwent perineal repair (2 of each with mesh). None have recurred with a median follow-up of 36 (range, 6-60) months. Perineal hernias are rare complications of abdominoperineal surgery with a more common prevalence after cancer operations. Smoking and chemoradiotherapy, but not corticosteroid immunosuppression, may be factors. The abdominal approach has advantages over the perineal approach, but both are suitable with good medium-term results.

Growth Factors as Treatment Options for Intestinal Inflammation

On the basis of several studies that have been completed to date, some growth factors appear promising for the treatment of inflammatory bowel disease: keratinocyte-like growth factor-2 (KGF-2), epidermal growth factor (EGF) enemas used in combination with oral mesalamine, somatropin (human growth hormone), and sargramostim (recombinant human GM-CSF). The results of these studies are highlighted and suggest that new insights into the regulation of intestinal immunity may provide effective synergistic or single-agent treatment alternatives to immunosuppression for inflammatory bowel disease. These data focus on the reparative components of mucosal homeostasis.

Review article: does the use of immunosuppressive therapy in inflammatory bowel disease increase the risk of developing lymphoma?

Recent case reports have raised concerns regarding the risks of non-Hodgkin's lymphoma in patients with inflammatory bowel disease treated with immunosuppressive agents. This evidence-based review examines this issue from data derived from the use of immunosuppression in other conditions (and inflammatory bowel disease). We conclude that, in transplant (cardiac and renal) recipients, immunosuppression increases the risk of non-Hodgkin's lymphoma. For non-transplant patients (with psoriasis and rheumatoid arthritis), debate remains as to whether the observed increase in the incidence of non-Hodgkin's lymphoma is due to drug or disease. For inflammatory bowel disease per se, population studies show no significant increase in the risk of non-Hodgkin's lymphoma, with a relative risk of 1.3 (95% confidence interval, 0.9-1.7) compared to expected rates, and several studies of immuno- suppression in inflammatory bowel disease do not appear to confirm a significant rate of lymphoma incidence. Reported cases of lymphoma from single centres should be viewed with caution as evidence of increased risk. If any association exists, it is likely to be of minimal clinical significance compared to the established and more frequent risks of myelosuppression and infection, and is unlikely to outweigh the benefit of immunosuppression in inflammatory bowel disease.