Initiation Of anti-TNF Therapy Research Articles

P487 Anti TNF induced psoariasiform skin eruptions are increasing in in the biosimilar era – a descriptive study of drug induced skin manifestations and their management

Abstract Background Skin disorders as extra-intestinal manifestations of inflammatory bowel disease 9IBD) are well recognized. In addition, contribution of drugs used in IBD in development of skin cancers is now fully understood. However, there are increasing reports of drug induced immune skin disorders resulting from or contributed by anti TNF agents. We aim to describe the etiology, manifestations and therapeutic approaches of anti TNF induced skin eruptions from a large tertiary center cohort. Methods A prospective database of IBD patients receiving biologics for IBD was interrogated for those who developed skin eruptions following initiation of anti-TNF therapy. We excluded patients who had pre-existing skin manifestations. All patients had dermatological expert review and confirmation of diagnosis as drug induced skin disorder. We collected their disease characteristics, time interval from initiation of biologics to development of skin disorder, the putative causative agent and the treatment of the skin lesions Results Sixty-eight patients (median age= 30 years, Female 44, male 24) among 1478 patients who received at least one dose of biologics developed a drug induced immune skin disorder. Median duration to development of skin lesions was 7.5 months. Anti TNF agents were responsible for 88.5% of the skin lesions with the commonest lesions being psoriasiform lesions in 34 (50%) patients. In our cohort, the psoriasiform lesions were more prevalent in patients who used biosimilar anti-TNF agents compared to the originator agent (31 vs 3). Forty patients required cessation of anti TNF agents because of skin eruptions. Twenty-eight of these were switched to ustekinumab with resolution of skin eruptions in 27 patients. Conclusion Anti TNF induced psoariasiform skin lesions appear to be more prevalent in the biosimilar era. Half of these patients will need treatment switch; ustekinumab appears to be an effective option in these patients

Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy—an observational follow-up study

BackgroundPoor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy.Methods32 children with IBD (21 with Crohn’s disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable.ResultsDuring follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared.ConclusionsThe fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.

A148 IMPACT OF EXAMINATION UNDER ANESTHESIA PRIOR TO ANTI-TUMOR NECROSIS FACTOR THERAPY ON FISTULA HEALING FOR PERIANAL CROHN’S DISEASE PATIENTS: A COMPARATIVE COHORT STUDY

Abstract Background Current guidelines recommend a combined approach consisting of an examination under anesthesia (EUA) and anti-TNF therapy for perianal Crohn’s Disease (PCD). However, the impact of this approach on fistula healing and long-term outcomes is unknown. Aims To assess the effect of EUA on fistula healing and long term outcomes in patients with perianal Crohn’s disese who are treated with anti-TNF therapy. Methods We performed a retrospective, single-center, comparative cohort study between 2009 and 2019. We compared patients with PCD who received EUA prior to anti-TNF therapy (combined therapy) to anti-TNF therapy alone. Our primary outcome was fistula closure by clinical assessment. Secondary outcomes included subsequent local surgery and fecal diversion. Logistic regression and multivariable cox-proportional hazard models adjusted for abscesses, concomitant immunomodulators, and time to anti-TNF initiation were performed. Results A total of 155 patients underwent 188 distinct anti-TNF starts: 66 (35%) after an EUA. Patients who underwent an EUA prior to anti-TNF therapy were more likely to have an abscess (50% vs. 15%; p < 0.001) and concomitant immunomodulator usage (64% vs. 50%; p = 0.07). Otherwise, there were no differences between cohorts in age, smoking status, disease duration, and location of luminal disease. There were no significant differences in fistula closure at 3, 6, or 12 months between cohorts overall (Table 1). The results remained consistent in sensitivity analyses that excluded patients with abscesses and prior biologic treatment failure. The results were also similar when defining the combined therapy group as those with setons. After a median follow-up of 4.6 years (IQR, 5.95) patients who underwent an EUA prior to anti-TNF therapy were more likely to require a subsequent EUA (aHR 2.2; 95% CI, 1.3–3.6) (Figure 1) but not fecal diversion (aHR 1.3; 95% CI, 0.45–3.9). Conclusions In this single center study, combined therapy (EUA prior to anti-TNF therapy) was not associated with improved clinical outcomes compared with anti-TNF therapy alone. These findings suggest that EUA may not be necessary in every patient with PCD prior to initiation of anti-TNF therapy. Future prospective studies that control for fistula complexity are warranted. Table 1: Unadjusted rates of fistula closure after anti-TNF therapy comparing patients with and without an exam under anesthesia Funding Agencies University of Ottawa Department of Medicine

O03 Continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?

Case report - IntroductionGolimumab is an anti-TNF alpha drug used in the treatment of inflammatory arthritis including spondyloarthritis (SpA). The introduction of this drug class has revolutionised the treatment of SpA over the last 20 years with significantly improved patient outcomes.Despite their treatment benefits multiple adverse effects of TNF-alpha inhibition have been reported through clinical trials including a possible increased risk of malignancy.We describe a case of a patient with known ankylosing spondylitis (AS) on golimumab who was diagnosed with low-grade prostate carcinoma and discuss the factors taken into consideration in guiding our decision-making process regarding ongoing treatment. Case report - Case descriptionA 57-year-old gentleman with known AS presented to the rheumatology clinic for routine review. His AS was well controlled, and he had been taking golimumab for the past 3 years. Upon review he was in clinical remission with a CRP <1 and ESR 5. Prior to the initiation of anti-TNF therapy his disease had been poorly controlled. However, following commencement his symptoms had significantly improved and he was able to work as a professional sports coach whilst bringing up a young family.On review he had recently been diagnosed with low-risk cancer of the prostate by his urologist. A prostate biopsy found Gleason 3 + 3 adenocarcinoma involving 2 out of 22 cores on each side, with a prostate specific antigen (PSA) of 3.95ng/ml. An MRI had shown chronic prostatitis. He was in the lowest risk category of grade group 1 prostate cancer and no treatment for his prostate cancer was indicated. The plan from his urology team was active surveillance with PSA monitoring.Whilst being investigated for possible malignancy his golimumab had been held for six months and during this period he had a significant flare in symptoms. He experienced severe back pain that forced him to stop working. Following his prostate cancer diagnosis, golimumab was restarted by his urologist with a subsequent improvement in his AS symptoms.To guide ongoing treatment his case was reviewed in the local biologics multi-disciplinary team meeting, alongside close communication with his urologist. The patient was informed of the risks of continuing golimumab in relation to his malignancy. Despite this he was reluctant to stop anti-TNF therapy or switch to another treatment, citing concerns about the impact it might have on his symptoms and ability to work.Case report - Discussion This case highlights the complexities involved in the management of a patient on anti-TNF therapy, who receives a diagnosis of malignancy, particularly when the diagnosis is classed as low risk. Traditionally anti-TNF therapy was contraindicated for patients with a history of a solid organ tumour within the previous five years. The British Society of Rheumatology (BSR) guidelines recommends that patients should be advised that there is no conclusive evidence for an increased risk of solid organ tumours but that on-going vigilance is required.A holistic patient-centred approach needs to be taken in these contexts, and consideration of cases on an individual basis is needed. Inter-disciplinary and multi-speciality team input, with the effective use of a biologics MDT, is crucial. The patient was understandably reluctant to stop his treatment due to the significant impact this may have on his quality of life.On liaison with his urologist his prostate cancer was in the lowest risk category with 99% 5-year survival rates with low risk of disease progression or spread.Evidence in this field to date has been conflicting and studies have predominantly focused on the safety of anti-TNFs in rheumatoid arthritis patients. Recent large national registry data has been reassuring. Few studies have looked at the AS and psoriatic arthritis anti-TNF treated population; however, a meta-analysis of RCTs found no evidence of increased incidence of malignancy.Taking into account his low-risk cancer, the patient’s wishes and clinical evidence in this field we have made to decision to continue anti-TNF treatment for now but with ongoing surveillance for any tumour progression. The patient will undergo urology follow up alongside regular PSA monitoring, and there will be a low threshold to stop or switch treatment in the futureCase report - Key learning pointsTreatment with anti-TNF therapy in patients with concomitant inflammatory arthritis and malignancy pose a specific challenge that require close co-ordination of care between rheumatologists, oncologists, other relevant teams and may benefit from the use of local biologics MDT to guide ongoing drug therapy.It is important to take a patient centred approach and consider cases on an individual basis taking into account their cancer diagnosis, extent of disease, histology findings and their response to TNF treatment.Patients must always be counselled on the risk of continuing anti-TNF and be involved in the decision-making process.Further research is required to look at the safety of anti-TNF particularly in SpA and if there is an increased risk of malignancy.

Continued 5ASA use after initiation of anti-TNF or immunomodulator confers no benefit in IBD: a population-based study.

With the advent of biological therapy in IBD, it is uncertain to what extent 5aminosalicylates (5ASA) are used. To explore whether or not 5ASA is continued once biological or immunomodulator therapy is initiated, and the outcomes in those who continued the 5ASAs. We conducted a retrospective cohort study using the population-based University of Manitoba IBD Epidemiologic Database which includes prescription drug dispensation from 1996 through 2018. We assessed outcomes among 5ASA users who continued versus discontinued 5ASA after initiation of anti-TNF therapy or immunomodulators. In all, 8379 (77%) of persons with IBD received at least one 5ASA dispensation (85% of ulcerative colitis, UC and 68% of Crohn's disease, CD). There was a reduction in later years, particularly for CD. The most common pattern of 5ASA use was intermittent at 65.1% (stopping and restarting use) versus one-time (4.1%), previous continuous (13.8%) and persistent (17%). Among the total IBD population use was 59% oral, 3% rectal and 14% combination. Of all 5ASA starts, only 25% were continued longer than 20 months. After immunomodulator or anti-TNF initiation, there was no difference in either UC or CD for negative outcomes (hospitalisation, surgery, corticosteroid starts, colorectal cancers or drug-related adverse events) between those who continued 5ASA versus those who discontinued. 5ASA remains commonly prescribed in UC and CD. Rates of persistent use in UC are low. Once an anti-TNF or immunomodulator is initiated, continuation of 5ASA seems to add no benefit.

Association of Anti–Tumor Necrosis Factor Therapy With Mortality Among Veterans With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is commonly treated with corticosteroids and anti-tumor necrosis factor (TNF) drugs; however, medications have well-described adverse effects. Prior work suggests that anti-TNF therapy may reduce all-cause mortality compared with prolonged corticosteroid use among Medicare and Medicaid beneficiaries with IBD. To examine the association between use of anti-TNF or corticosteroids and all-cause mortality in a national cohort of veterans with IBD. This cohort study used a well-established Veteran's Health Administration cohort of 2997 patients with IBD treated with prolonged corticosteroids (≥3000-mg prednisone equivalent and/or ≥600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy from January 1, 2006, to October 1, 2015. Data were analyzed between July 1, 2019, and December 31, 2020. Use of corticosteroids or anti-TNF. The primary end point was all-cause mortality as defined by the Veterans Health Administration vital status file. Marginal structural modeling was used to compare associations between anti-TNF therapy or corticosteroid use and all-cause mortality. A total of 2997 patients (2725 men [90.9%]; mean [SD] age, 50.0 [17.4] years) were included in the final analysis, 1734 (57.9%) with Crohn disease (CD) and 1263 (42.1%) with ulcerative colitis (UC). All-cause mortality was 8.5% (n = 256) over a mean (SD) of 3.9 (2.3) years' follow-up. At cohort entry, 1836 patients were new anti-TNF therapy users, and 1161 were prolonged corticosteroid users. Anti-TNF therapy use was associated with a lower likelihood of mortality for CD (odds ratio [OR], 0.54; 95% CI, 0.31-0.93) but not for UC (OR, 0.33; 95% CI, 0.10-1.10). In a sensitivity analysis adjusting prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after initiation of anti-TNF therapy, the OR for UC was statistically significant, at 0.33 (95% CI, 0.13-0.84), and the OR for CD was 0.55 (95% CI, 0.33-0.92). This study suggests that anti-TNF therapy may be associated with reduced mortality compared with long-term corticosteroid use among veterans with CD, and potentially among those with UC.

The Risk of Rheumatoid Arthritis, Psoriasis, and Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease Exposed to Anti-TNF: A Nationwide Danish Cohort Study

Background: Anti-TNF medications are effective therapies for rheumatoid arthritis (RA), psoriasis, hidradenitis suppurativa, and inflammatory bowel diseases, however, case reports have identified the occurrence of these diseases following initiation of anti-TNF therapy. We assessed the risk of RA, psoriasis, and hidradenitis suppurativa associated with anti-TNF therapies in patients with inflammatory bowel disease. Methods: A performed a nationwide Danish population-based cohort study, 2005-2018, to assess the effect of anti-TNF therapy on first occurrence of RA, psoriasis, or hidradenitis suppurativa (as a combined outcome and separately). Propensity scores were estimated based on covariates including comorbidities and co-medications, and anti-TNF exposed and unexposed patients were matched on propensity scores. We also compared the risk of RA, psoriasis, and hidradenitis suppurativa associated with anti-TNF monotherapy vs. azathioprine monotherapy. Findings: Our cohort included 9,036 anti-TNF exposed patients and 9,036 unexposed patients. The median age of anti-TNF exposed patients was 36 years (Q1-Q3: 26-48), 53% were female, and 50% had Crohn’s disease, while for unexposed patients the corresponding figures were 38 years (Q1-Q3: 28-51), 53%, and 48%. Anti-TNF therapy was associated with a significantly increased risk of the combined outcome (HR 1∙37, 95% CI 1∙12-1∙68), and with numerically increased HRs for RA (HR, 1∙60; 95% CI 0∙78-3∙31), psoriasis (HR, 1∙32; 95% CI 1∙05-1∙66), and hidradenitis suppurativa (HR, 1∙64; 95% CI 0∙86-3∙12). When compared to azathioprine monotherapy, anti-TNF monotherapy was also associated with a significantly increased risk of the combined outcome (HR 2∙42, 95% CI 1∙27-4∙62), with a 5-fold increased risk of RA (HR 5∙10, 95% CI 1∙03-25∙28). Interpretation: In this nationwide population-based cohort, anti-TNF therapy was, paradoxically, associated with an increased risk of RA, psoriasis, and hidradenitis suppurativa. These data are unexpected and warrant further investigation. Funding Information: This study was financially supported by the Danish National Research Foundation, grant no. DNRF148. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethics approval is not required for register based epidemiological research in Denmark.

Vaccination prior to initiation of anti-TNF therapy

Vaccination prior to initiation of anti-TNF therapy

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events

PurposeTo assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years.MethodsNinety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed.ResultsIn older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185–12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098–9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248–66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity.ConclusionOlder patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

P550 Long-term effectiveness of anti-TNF agents in symptomatic stricturing Crohn’s disease

Abstract Background Approximately one half of the patients with Crohn’s disease (CD) develop intestinal strictures during their lifetime. The effectiveness of currently approved drugs in fibrosis-predominant lesions is very limited. Our aim was to determine the effectiveness of anti-TNF therapy in CD complicated by symptomatic intestinal strictures in a real-world setting. Methods We included adult patients with symptomatic stricturing CD receiving their first-line anti-TNF therapy. Strictures were defined as constant luminal narrowing with pre-stenotic dilatation. We excluded those patients with previous anti-TNF exposure, surgery or endoscopic therapy of the stenosis. The effectiveness of the anti-TNF was defined as a composite outcome combining the persistence of the treatment and without dose or frequency intensification, with no new immunomodulators, surgery or endoscopic therapy during follow-up. A multivariate Cox regression was performed and the final multivariate model was determined using a backward procedure. Results A total of 262 patients from 32 sites were included (141 received infliximab and 121 adalimumab). The median number of stenosis per patient was 1 (range 1–9). The treatment was effective in 81% and 59% of patients after 6 and 12 months, respectively, while this outcome was fulfilled by 21% after a median of 40 months (IQR, 19–85). During follow-up, anti-TNF therapy required a dose or frequency adjustment in 39% of patients, 12% required a new immunomodulator or endoscopic therapy in 4%. The proportion of subjects requiring surgery was 15% and 21% after 1 and 2 years, respectively, with an overall rate of surgery of 32%. Infliximab was associated with a higher rate of surgery as compared with adalimumab (OR 1.78; 95% CI, 1,025-3,09). A shorter time since the diagnosis of CD or the stricture and the initiation of anti-TNF therapy was associated with a greater effectiveness at 6 and 12 months (HR 0.99 95% CI 0.99–1, p = 0.045; HR 0.99 95% CI 0.99–0.99, p = 0.015; HR 0.98 95% CI 0.96–0.99, p = 0.024; HR 0.99 95% CI 0.98–1.0, p = 0.046; respectively). In the survival analysis, younger age, lower albumin levels at baseline, strictures being located in the descending colon, concomitant use of mesalamine and the presence of ulcers or lymphadenopathy at the stricture were associated with lower effectiveness. The anti-TNF agent was discontinued in 131 patients (50%), and 88 subjects (34%) required a switch to a new biologic. Conclusion Anti-TNF agents are effective in approximately 20% of patients with CD complicated with symptomatic strictures. Early introduction of anti-TNF therapy improves the effectiveness in the short term in these patients. Some clinical and radiological predictors can identify patients with a lower probability of response.

2929 Correlation of Body Mass Index (BMI) and C-Reactive Protein (CRP) With Inflammatory Bowel Disease Progression in an Urban, Afro-Caribbean Population

INTRODUCTION: Inflammatory Bowel Disease (IBD) is associated with changes in body composition of patients. Recent studies have shown that the prevalence of obesity is rising in patients with IBD, where 15-40% of adults are obese and 20-40% are considered overweight. One prospective study analyzed body composition in IBD patients overtime and noted that despite an overall increase in adiposity, the total muscle mass was decreased. Low lean muscle mass has an association with poor response to therapy, surgical outcomes and the quality of life in IBD patients. Low C-reactive protein (CRP) levels after initiation of anti-TNF therapy have been associated with mucosal healing on surveillance colonoscopies and clinical disease remission. The aim of this study is to analyze the association between BMI and CRP with progression of IBD, using anti- TNF use as a surrogate marker for disease severity. METHODS: Medical records at Kings County Medical Center in Brooklyn, New York were queried for patients with the ICD 9 and 10 code diagnoses for Crohn's disease (CD) and Ulcerative Colitis (UC) from 2015 to 2018. Biographical, laboratory and endoscopic data, including BMI and CRP, was collected and analyzed. RESULTS: 148 patients with IBD were analyzed from 2015-2018; where 57.2% had UC and 42.8% had CD. Mean age of patients was 47.4 years, and 53.4% of patients were females. The average BMI prior to initiation of therapy was 27.6 kg/m2. The average years diagnosed with IBD was 11.1 years. Of the total patients, 37 were on biologic therapy. In the BMI group, the odds ratio was 0.905 indicating that patients with a lower BMI had more severe disease. The P value was 0.068, not significant but trended towards significance. In the CRP group, the odds Ratio was 1.020, which signified that patients with higher CRP values had more severe disease, with a P value of 0.046. CONCLUSION: The results of our small retrospective study suggest that a lower BMI and higher CRP are independent predictors of severe disease. Our study demonstrated that severe IBD, as measured by anti-TNF use, is associated with high CRP levels. We believe that low BMI and high CRP measurements may be used in conjunction with endoscopic findings and clinical presentation to escalate therapy early preventing worsening of disease. Further studies can be done to also incorporate endoscopic scoring system on surveillance colonoscopies to confirm the correlation between lower BMI and higher CRP with severity of disease.

Stopping Mesalamine Therapy in Patients With Crohn’s Disease Starting Biologic Therapy Does Not Increase Risk of Adverse Outcomes

Little is known about the effects of discontinuing mesalamine therapy for patients with Crohn's disease (CD) who initiate therapy with an anti-tumor necrosis factor (anti-TNF) agent. We analyzed data from 2 national population cohorts to compare outcomes of patients with CD already on mesalamine therapy who started treatment with an anti-TNF agent and then either stopped or continued mesalamine. The primary outcome was any adverse clinical event, defined as a composite of new corticosteroid use or CD-related hospitalization or surgery. We collected data from the Truven MarketScan (IBM, Armonk, NY) health claims database in the United States and the Danish health registers. Our analysis included patients with CD who started anti-TNF therapy after at least 90 days of oral mesalamine therapy. Patients were classified as stopping mesalamine if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors, and health care utilization. Adjusted hazard ratios with 95% CIs were calculated, comparing stopping mesalamine with continuing mesalamine. A total of 3178 patients with CD were included in our final analysis (2960 in the United States and 218 in Denmark). Stopping mesalamine after initiating anti-TNF therapy was not associated with an increased risk of adverse clinical events in the US cohort (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.03; P= .13) or in the Danish cohort (adjusted hazard ratio, 1.13; 95% CI, 0.68-1.87; P= .63). Similar results were obtained from sensitivity analyses of concomitant immunomodulator use and duration of mesalamine treatment before initiation of anti-TNF therapy. In a retrospective analysis of 2 national databases, we found that stopping mesalamine therapy for patients with CD who were starting anti-TNF therapy did not increase their risk of adverse clinical events. These results should be validated in a prospective study.

P077 Tuberculosis in inflammatory bowel disease patients from a referral center in Salvador-Bahia, Brazil

BACKGROUND: In the last decade, potent immunosuppressive therapy has become the standard treatment for inflammatory bowel disease (IBD) (1). However, the increasingly use of immunomodulators associated to biological therapy—especially the inhibitors of tumor necrosis factor alpha (TNF-α)—have considerably increased the cases of tuberculosis (TB) in IBD patients (2,3). Meanwhile, Brazil is a high TB burden country, with 87,000 new cases per year, and the state of Bahia reports more than 3,600 new cases annually (4,5). METHODS: Were included IBD patients under treatment followed at a referral center from August 2017 to July 2018. The IBD was diagnosed according to the guideline criteria of was according to the criteria the European Crohn's and Colitis Organizsation. Diagnosis of latent TB infection (LTBI) was based on tuberculin skin test (TST) induration ≥5 mm without evidence of clinically manifested active tuberculosis (TB). The development of active TB, diagnosed during the treatment for inflammatory bowel disease, was based on symptoms, TST, chest X ray and laboratory finding. In addition, Sstatistical analysies was performed using the statistical software package SPSS version 21.0 for Windows. A P-value less than 0.05 was considered statistically significant. RESULTS: Of the 302 patients evaluated, 185 were submitted to screening for LTBI and 24 (12.9%) were positive. Of the total sample, 8 (2.6%) developed active TB during treatment for IBD. Six cases occurred despite theof negative screening for LTBI and 2 cases occurred even after chemoprophylaxis with isoniazid. Among 186 UC patients, 4 (2.1%) developed active TB and all cases were pulmonary TB. Two patients were under azathioprine monotherapy (?) with azathioprine and 2 were using 5-ASA derivatives without immunosuppressant. Among 116 Crohn disease (CD) patients, 4 (3.4%) developed active TB, 2 cases of pulmonary TB and 2 cases of pleural TB. All patients with CD who developed active TB were under anti-TNF therapy, 2 under treatment with infliximab monotherapy and 2 with adalimumab combotherapy associated with azathioprine. In total, 63 (20.9%) patients were under biological therapy. The frequency of active TB disease among patients exposed to anti-TNF when compared to patients not exposed was 6.3% (4/63) and 1.7% (4/239), respectively, and the difference was significant (P = 0.047) between those groups. The median time between initiation of anti-TNF therapy and the diagnosis of TB was 19 months (range: 3.0–45.0). CONCLUSION(S): The frequency of latent TB in our center is comparable to the frequency described in IBD patients from endemic countries. It was observed a high frequency of active TB in IBD patients under anti-TNF therapy from a reference center in Brazil. ACKNOWLEDGMENT: Fellowship Program from University of the State of Bahia (PICIN UNEB).

Inflammatory bowel disease and mycobacteria: how much can we trust isoniazid prophylaxis during antitumor necrosis factor therapy?

Isoniazid (INH) prophylaxis is recommended for the prevention of tuberculosis (TB) reactivation before or/and during initiation of treatment with tumour necrosis factor antagonists (anti-TNF agents). Nonetheless, the long-term effectiveness of chemoprophylaxis is not clear. In this study, we aimed to evaluate the characteristics of patients who developed TB reactivation in spite of INH prophylaxis associated with anti-TNF treatment. In this retrospective study, medical records of 1263 patients with inflammatory bowel disease were reviewed. Baseline TB screening tests (purified protein derivative test and/or QuantiFERON-TB Gold test) were performed on all patients before initiation of anti-TNF therapy. Patients with purified protein derivative of more than 5 mm and/or a positive result of the QuantiFERON-TB Gold test received INH prophylaxis for 9 months. We analysed the data of patients diagnosed with TB reactivation during the anti-TNF treatment despite INH chemoprophylaxis. Overall, 175 patients underwent anti-TNF treatment. Sixty of these 175 patients had pretreatment testing showing latent TB infection and therefore were treated concomitantly with INH for 9 months in addition to their anti-TNF treatment. TB reactivation occurred in four of these 60 co-INH/anti-TNF treated patients. Active TB was diagnosed after 37.5±27 (range: 18-84) months of anti-TNF treatment. In two of the four patients that active TB was diagnosed, was also detected other Mycobacterium spp.: M. bovis in one patient and M. genavense in the other one. INH chemoprophylaxis may not prevent the reactivation of TB during anti-TNF therapy in the long-term. Patients should be carefully and periodically screened for TB reactivation during anti-TNF therapy.

Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn's Disease

Few data are available on the effects of tumor necrosis factor (TNF) antagonist therapy for patients with internal fistulizing Crohn's disease (CD) and there is debate regarding the risk of abscess. We aimed to assess the long-term efficacy and safety of anti-TNF therapy for patients with internal fistulas. We performed a retrospective study of data collected from the Groupe d'Etude Thérapeutique des Affections Inflammatoires Digestives trial, from January 1, 2000, through December 31, 2017. Our final analysis included 156 patients who began treatment with an anti-TNF agent for CD with internal fistula (83 men; median disease duration, 4.9 y). The primary end point was the onset of a major abdominal surgery. Secondary analysis included disappearance of the fistula tract during follow-up evaluation and safety. The Kaplan-Meier method was used for statistical analysis. After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy. In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

Mo1871 - Direct Costs of Care Among Patients with Inflammatory Bowel Disease before and after Initiation of Anti-TNF Therapy

Mo1871 - Direct Costs of Care Among Patients with Inflammatory Bowel Disease before and after Initiation of Anti-TNF Therapy

Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared With Antitumor Necrosis Factor-α-Directed Therapy for Inflammatory Bowel Disease.

Objectives:Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD.Methods:A retrospective cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to 2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12-month period or new initiation of anti-TNF therapy, each treated as time-updating exposures. The primary outcome was all-cause mortality. Secondary outcomes included common causes of death. Marginal structural models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use relative to corticosteroids.Results:Among patients with CD, 7,694 entered the cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new anti-TNF users, respectively. The risk of death was statistically significantly lower in patients treated with anti-TNF therapy for CD (21.4 vs. 30.1 per 1,000 person-years, OR 0.78, 0.65–0.93) but not for UC (23.0 vs. 30.9 per 1,000 person-years, OR 0.87, 0.63–1.22). Among the CD cohort, anti-TNF therapy was also associated with lower rates of major adverse cardiovascular events (OR 0.68, 0.55–0.85) and hip fracture (OR 0.54, 0.34–0.83).Conclusions:Compared with prolonged corticosteroid exposure, anti-TNF drug use was associated with reduced mortality in patients with CD that may be explained by lower rates of major adverse cardiovascular events and hip fracture.

Temporal Trends in Initiation of Therapy With Tumor Necrosis Factor Antagonists for Patients With Inflammatory Bowel Disease: A Population-based Analysis.

Anti-tumor necrosis factor (anti-TNF) agents are effective treatments for Crohn's disease (CD) and ulcerative colitis (UC). We aimed to determine their patterns of use and changes in these patterns over time, as well as use of immunomodulators and corticosteroids before anti-TNF therapy for persons with inflammatory bowel diseases. We used the University of Manitoba IBD Epidemiology Database to identify all anti-TNF users with CD and UC from 2001 through 2014. We assessed changes in the prevalence and incidence of anti-TNF use during different time periods (April 2001-March 2005, April 2005-March 2009, or April 2009-March 2013). We also characterized patterns of corticosteroid use, corticosteroid dependence, and immunomodulator use before anti-TNF administration and determined how these changed over time. The primary end point was change in time to first receipt of anti-TNF among the different time periods. We identified 950 persons (761 with CD and 189 with UC) who received anti-TNF agents. The cumulative prevalence of persons with current or prior anti-TNF exposure in 2014 was 20.4% for CD and 6.0% for UC. In 2014 the cumulative incidence values of anti-TNF exposure within 5 years of diagnosis were 23.4% for patients with CD and 7.8% for patients with UC. Most users of anti-TNF agents had evidence of corticosteroid dependence (more than 2 g prednisone within any 12-month period) before initiation of anti-TNF therapy. Cumulative corticosteroid exposure before anti-TNF use decreased over time for patients with UC, but not significantly for patients with CD. There was no increase over time in the use of concomitant immunomodulators with anti-TNF therapy. Use of anti-TNF agents increased from 2001 through 2014, with a concomitant significant decrease in cumulative use of corticosteroids before anti-TNF therapy for patients with UC. However, there has been no reduction in cumulative use of corticosteroids before anti-TNF therapy for patients with CD and no change in use of immunomodulators by patients with CD. These findings indicate a continuing need for optimization of anti-TNF therapy for patients with inflammatory bowel disease.

P455 Clinical features of tuberculosis infection in inflammatory bowel disease patients on anti-TNF therapy

Background: According to the WHO the incidence of active tuberculosis (TB) in Spain is high 13 cases per 100.000 inhabitants, reaching in Galicia (a region located in the North-west of Spain 20 cases per 100.000 inhabitants. Otherwise patients on anti-TNF treatment have an increased risk of active TB too. We aimed to analyze the clinical features of active tuberculosis infection in inflammatory bowel diseases (IBD) patients on anti-TNF drugs. Methods: We perform a case-control study. Our database was searched for IBD patients on anti-TNF who developed active TB from 2000 to 2014. Controls were selected among patients with active TB infection matched for sex, age and year of diagnosis of tuberculosis. All their clinical features were analyzed and in the statistical analysis p values below 0.05 were considered significant. Results: The incidence of active TB in IBD patients on anti-TNF drugs was 3.4% (10/290). The median time to the development of active TB after initiation of anti-TNF therapy was 6 months range (2–60). TB skin test (TST) was performed in 90% cases, but only 50% had two-step TST. Three patients had a positive TST and received anti-TB prophylaxis. Prior antiTNF chest radiographies do not suspected TB. Previous TB exposition, time from symptoms to TB diagnosis and hospital stay were similar to controls. IBD patients had a higher laboratory identification of mycobacterium TB prior antiTB treatment (p=0.03) and had previous 3 months exposition to steroids or inmunodepressant (p=0.01) than controls. They suffered from more extrapulmonary TB (p=0.01) with primary resistances to antiTB drugs (p=0.03), had to receive TB treatment for a longer time (p=0.04) and had more complications related to TB p=0.008) than controls. Conclusions: IBD patients on anti-TNF drugs suffer from more complicated extrapulmonary and drug-resistant TB infections, needing longer course of TB treatment. In these patients two-step TST must be performed and positive findings must be treated.

Mo1887 Early Initiation of Anti-TNF Therapy Does Not Reduce Colectomy or Hospitalization Rates in Ulcerative Colitis: A Retrospective Cohort Study

Mo1887 Early Initiation of Anti-TNF Therapy Does Not Reduce Colectomy or Hospitalization Rates in Ulcerative Colitis: A Retrospective Cohort Study