Subject(s)
Immunocompromised Host , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/immunology , Opportunistic Infections/immunology , Humans , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Opportunistic Infections/complications , Opportunistic Infections/diagnosis , Opportunistic Infections/therapy , VaccinationABSTRACT
OBJECTIVES: Immunosuppressant therapies (IMTs; thiopurines, anti-tumor necrosis factor agents) may influence the immunologic control of cancer and might facilitate the spread and recurrence of cancer. This study assesses the impact of the use of IMTs on the development of incident cancers (recurrent or new) in patients with inflammatory bowel disease (IBD) and a history of malignancy. METHODS: Patients with IBD included in the ENEIDA registry with a history of cancer without being exposed to IMTs were identified and retrospectively reviewed and compared regarding further treatment with IMTs or not by means of a log-rank test. RESULTS: Overall, 520 patients with previous extracolonic cancer naive to IMTs before the diagnosis of cancer were identified. Of these, 146 were subsequently treated with IMTs (exposed), whereas 374 were not (nonexposed). The proportion of patients with incident cancers was similar in both exposed (16%) and nonexposed (18%) patients (P = 0.53); however, there was more than a 10-year difference in the age at index cancer between these 2 groups. Cancer-free survival was 99%, 98%, and 97% at 1, 2, and 5 years in exposed patients, and 97%, 96%, and 92% at 1, 2, and 5 years in non-exposed patients, respectively (P = 0.03). No differences in incident cancer rates were observed between exposed and nonexposed patients when including only those who were exposed within the first 5 years after cancer diagnosis. DISCUSSION: In patients with IBD and a history of cancer not related to immunosuppression, the use of IMTs is not associated with an increased risk of new or recurrent cancers even when IMTs are started early after cancer diagnosis.
Subject(s)
Immunosuppressive Agents , Inflammatory Bowel Diseases , Neoplasms , Female , Humans , Immunomodulation/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/classification , Incidence , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged , Neoplasms/chemically induced , Neoplasms/epidemiology , Neoplasms/immunology , Neoplasms/pathology , Outcome and Process Assessment, Health Care , Registries , Risk Assessment , Risk Factors , Spain/epidemiology , Time-to-Treatment/statistics & numerical dataABSTRACT
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
Subject(s)
Antirheumatic Agents/therapeutic use , Infections/epidemiology , Inflammatory Bowel Diseases/drug therapy , Pregnancy Complications/drug therapy , Premature Birth/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab/therapeutic use , Adult , Case-Control Studies , Certolizumab Pegol/therapeutic use , Child, Preschool , Cohort Studies , Europe/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Infliximab/therapeutic use , Kaplan-Meier Estimate , Male , Multivariate Analysis , Pregnancy , Proportional Hazards Models , Retrospective StudiesABSTRACT
BACKGROUND: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). AIM: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. METHODS: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). RESULTS: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). CONCLUSIONS: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.
Subject(s)
Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/therapy , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Case-Control Studies , Disease Progression , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Phenotype , Retrospective Studies , Spain/epidemiology , Young AdultABSTRACT
OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.
Subject(s)
Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/complications , Neoplasms/epidemiology , Smoking/adverse effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Age Factors , Female , Humans , Incidence , Male , Middle Aged , Prevalence , Registries , Spain/epidemiologyABSTRACT
BACKGROUND: Idiopathic bile acid malabsorption (BAM) has been suggested as a cause of chronic watery diarrhoea, with a response to colestyramine in 70% of patients. However, the efficacy of this drug has never been investigated in placebo-controlled trials. AIM: To evaluate the efficacy of colestyramine as compared with hydroxypropyl cellulose in the treatment of functional chronic watery diarrhoea. METHODS: Patients with chronic watery diarrhoea were randomly assigned to groups given colestyramine sachets 4 g twice daily (n = 13) or identical hydroxypropyl cellulose sachets (n = 13) for 8 weeks. The primary end-point was clinical remission defined as a mean of 3 or fewer stools per day during the week before the visit, with less than 1 watery stool per day. A secondary end-point was the reduction in daily watery stool number. SeHCAT test was performed in all patients, but an abnormal test was not a prerequisite to be included. RESULTS: All included patients had a SeHCAT 7-day retention ≤20%. There were no statistical differences in the percentage of patients in clinical remission at week 8 between colestyramine and hydroxypropyl cellulose with either intention-to-treat (53.8% vs. 38.4%; P = 0.43) or per-protocol (63.6% vs. 38.4%; P = 0.22) analyses. However, the mean per cent decrease in watery stool number was significantly higher with colestyramine than with hydroxypropyl cellulose (-92.4 ± 3.5% vs. -75.8 ± 7.1%; P = 0.048). The rate of adverse events related to study drugs did not differ between groups. CONCLUSIONS: Colestyramine (4 g twice daily) is effective and safe for short-term treatment of patients with chronic watery diarrhoea presumably secondary to BAM. Clinical Trials Register number EudraCT 2009-011149-14.
Subject(s)
Bile Acids and Salts/metabolism , Cellulose/analogs & derivatives , Cholestyramine Resin/therapeutic use , Diarrhea/drug therapy , Adult , Cellulose/therapeutic use , Diarrhea/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Taurocholic Acid/analogs & derivativesABSTRACT
AIMS: Assess IBD patients starting anti-TNF for the impact of preventive measures in HBV and/or HCV, and the predictive response factors to HBV vaccination. METHODS: Multicenter prospective study including 389 IBD patients. Four interventions were established: I-1) anti-HBs <100IU/L: HBV vaccination with double doses at 0-1-2months, and revaccination if titres <100IU/L (seroprotection defined as anti-HBs10-100IU/L and effective vaccination anti-HBs >100IU/L); I-2) anti-HBs >100IU/L (previous effective vaccination): monitoring levels; I-3) anti-HBc and/or HCV+: analysis every two months; I-4) HBsAg+: start anti-virals. RESULTS: I-1 and I-2) For first vaccination, effective vaccination and seroprotection were obtained in 26.4% and 43.5%, and for revaccination 31.3% and 44.4%, respectively. Predictive factors of effective vaccination were age ≤30years (OR=2.2) and being vaccinated simultaneously with anti-TNF (OR=5.2) instead of late vaccination, whereas age ≤30years (OR=2.6) and anti-TNF monotherapy (OR=2.4) were predictive for seroprotection. 80.8% of patients previously vaccinated maintained titres at 29months follow-up. The only factor related to maintaining titres was previous vaccination versus achieving effective vaccination during anti-TNF (HR=2.49); I-3 and I-4) HBV-DNA + without reactivation was detected in 7% of 29 anti-HBc. No reactivation was found in the remaining HCV (n=5) or HBsAg (n=4) patients. CONCLUSIONS: 1) Response to vaccination/revaccination is low in patients with anti-TNF. Young patients vaccinated at the beginning of anti-TNF and receiving it as a monotheraphy showed better response. 2) Long-lasting effective vaccination is greatest in patients previously vaccinated. 3) Following-up the established surveillance and/or preventive anti-viral therapy seems to be safe in HBV and HCV patients.
Subject(s)
Hepatitis B/immunology , Hepatitis C/immunology , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Vaccination , Watchful Waiting , Adalimumab , Adult , Age Factors , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Certolizumab Pegol , DNA, Viral/blood , Female , Hepacivirus/genetics , Hepatitis B/drug therapy , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines , Hepatitis B virus/genetics , Hepatitis B virus/physiology , Humans , Immunization, Secondary , Immunoglobulin Fab Fragments/therapeutic use , Inflammatory Bowel Diseases/immunology , Infliximab , Male , Polyethylene Glycols/therapeutic use , Prospective Studies , RNA, Viral/blood , Time Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Virus Activation , Young AdultABSTRACT
BACKGROUND: Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. AIM: To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. METHODS: Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. RESULTS: One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3-8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). CONCLUSIONS: Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Adolescent , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/adverse effects , Drug Administration Schedule , Drug Eruptions/epidemiology , Drug Evaluation , Drug Therapy, Combination , Female , Follow-Up Studies , Gastrointestinal Agents/adverse effects , Humans , Hydrocortisone/therapeutic use , Infections/chemically induced , Infections/epidemiology , Inflammatory Bowel Diseases/epidemiology , Infliximab , Infusions, Intravenous/adverse effects , Male , Middle Aged , Neoplasms/chemically induced , Neoplasms/epidemiology , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Serum Sickness/chemically induced , Serum Sickness/epidemiology , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Infliximab (IFX) could change the course of Crohn's disease (CD) by reducing steroid use, surgery or prompting earlier introduction of immunomodulators (IMM). AIM: To evaluate the impact of IFX availability on the course of early CD. METHODS: Two cohorts of newly diagnosed CD patients were identified: The first cohort included patients diagnosed from January 1994 to December 1997 and the second from January 2000 to December 2003. All patients were diagnosed, treated and followed up in the same centre until December 1999 (first cohort) or December 2005 (second cohort). Development of disease-related complications, steroid, IMM or IFX requirements and intestinal resections during follow-up were registered. RESULTS: A total of 328 patients were included (146 first cohort, 182 second cohort). A similar proportion of patients in both cohorts received steroids, but steroid exposure resulted significantly more intense in the first cohort (P = 0.001). In the second cohort, 14% of patients received IFX. Thiopurines were used more (P = 0.001) and earlier (P = 0.012) in the second cohort. No differences in surgical requirements or the development of disease-related complications were found. CONCLUSIONS: Following a step-up therapeutic algorithm, IFX availability did not reduce surgical requirements or the development of disease-related complications.