Anti-tumour Necrosis Factor Drugs Research Articles

The Impact of Psoriasis Treatments on the Risk of Skin Cancer: A Narrative Review.

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

Preventing Recurrence of Crohn's Disease Post-Ileocaecal Surgery in Paediatric Patients: A Therapy Guide Based on Systematic Review of the Evidence.

Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review(SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patientsundergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.

Brucellosis in a patient with Crohn's disease treated with infliximab: A case report

Crohn's disease (CD) is an inflammatory disease that can affect any part of the gastrointestinal tract and presents with myriad symptoms. Various treatments, including biological treatments, are available. The use of biologics increases the risk of opportunistic infections, with no association with serious infections (1). To the best of our knowledge, there are no established recommendations or case studies for patients with CD infected with Brucella being actively treated with biologics and immunomodulators to date. Herein, we report the first case of brucellosis diagnosed in a patient with CD treated with biologics and immunomodulators.A 40-year-old man had been treated with anti-tumour necrosis factor (anti-TNF) drugs, namely, infliximab and azathioprine, for CD for the past eight years. During a follow-up visit, the patient complained of loss of appetite, fever, weight loss, and joint discomfort. The patient reported a history of raw milk consumption. Blood cultures indicated the growth of Brucella species. Infliximab and azathioprine were held, and brucellosis treatment was initiated, including rifampin 600 mg once daily, doxycycline 100 mg twice daily, and streptomycin 1 g intramuscularly daily. A multidisciplinary team comprising gastroenterologists and infectious disease specialists decided to initiate brucellosis treatment and resume biologics and immunomodulators 4 weeks after starting Brucella treatment.

P897 The association of HLA-DQA1*05 carriage with immunogenicity to anti-tumour necrosis factor therapy and drug persistence in Asian patients with inflammatory bowel disease

Abstract Background HLA-DQA1*05 carriage increases anti-tumour necrosis factor (TNF) immunogenicity and lowers drug persistence in European inflammatory bowel disease (IBD) patients. There is a paucity of data for Asian patients. We hypothesize that the HLA-DQA1*05 allele is present in our local IBD population and may be associated with similar clinical and pharmacokinetic outcomes as European cohorts. Methods A single-centre retrospective study of consecutive IBD patients on Infliximab (IFX) or Adalimumab (ADM) was performed. HLA-DQA1*05 carriage was tested with Sanger sequencing. Serum anti-drug antibody (ADA) levels were analysed at each IFX infusion and per physician discretion for ADM. Concomitant immunomodulator (IM) therapy with Azathioprine or Methotrexate was recorded. Primary outcome was immunogenicity to IFX or ADM, defined as ADA concentration ≥10 AU/ml at any time point. Secondary outcomes were loss of response (LOR), defined as IBD symptom-related treatment intensification, and persistence, defined as anti-TNF continuation at end of follow-up. The effects of HLA-DQA1*05 carriage on outcomes and predictors of persistence were analysed. Results 39 patients (28 Crohn’s disease, 11 ulcerative colitis) were included (mean age 39 years, median disease duration 10 years). 24 patients had IFX as first anti-TNF agent (21 with IM, 3 as monotherapy), 7 of whom had second-line ADM with IM. 15 patients had ADM as first anti-TNF agent (13 with IM, 2 as monotherapy), 2 of whom had second-line IFX (1 with IM). 15/39 (38.5%) patients were positive for HLA-DQA1*05. 42/48 (87.5%) of anti-TNF exposures were on IM. In HLA-DQA1*05 carriers compared to non-carriers, development of ADA (61.1% vs 47.8%, p=0.397) and LOR (42.1% vs 31.0%, p=0.433) was numerically higher but not statistically different. Persistence of first anti-TNF agent was similar between carriers and non-carriers at the end of follow-up (median 28.0 months vs 21.5 months, p=0.364) (Figure 1). ADA development was not associated with LOR (p=0.07) or persistence (p=0.29). 19/48 (39.6%) of anti-TNF exposures discontinued treatment at the end of follow-up, 13 of whom experienced LOR. 10/13 (76.9%) of patients with LOR were female. Female sex was significantly associated with anti-TNF non-persistence on univariable (OR 4.82, 95% CI 1.38-16.75, p=0.01) and multivariable logistic regression (OR 7.24, 95% CI 1.35-38.90, p=0.02), after adjusting for HLADQA1*05 carriage, presence of ADA and anti-TNF order (first versus second-line) (Table 1). Conclusion In Asian IBD patients, HLA-DQA1*05 carriage may not affect immunogenicity nor treatment persistence, especially with proactive therapeutic drug monitoring and concurrent IM. Female sex negatively affects persistence. Larger prospective studies are needed.

Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

BackgroundDespite research, there are still controversial areas in the management of Crohn’s disease (CD).ObjectiveTo establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.MethodsClinical controversies...

Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.

Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 μg/mL for infliximab and 6.0 μg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 μg/mL versus 5.5 μg/mL for infliximab (P = 0.72) and 6.0 μg/mL versus 9.9 μg/mL for adalimumab (P = 0.34). Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.

Leprosy in French Guiana, 2015 to 2021: Dynamics of a Persistent Public Health Problem

A resurgence of leprosy as a public health problem in French Guiana was reported over the period 2007 to 2014, particularly among Brazilians gold miners. Prolonged multidrug therapy and reversal reactions represent a therapeutic challenge. The objective of this study was to assess the evolution of leprosy in this European overseas territory. All patients with leprosy confirmed in histopathology between 1 January 2015 and 31 December 2021 were included. A total of 86 patients were included, including 64 new cases and 22 previously diagnosed cases. Sixty patients (70%) were male, 6 cases were paediatric. Brazilian gold miners represented 44.1% of reported occupations (15/34). Maroons represented the second community (13 patients, 15%). Multibacillary and paucibacillary forms were found in 53 (71%) and 22 (29%) patients, respectively. The annual prevalence never exceeded the threshold of 1/10,000. The mean incidence and prevalence were significantly lower than during the period 2007 to 2014 (p < 0.0001). Reversal reactions were found in 29 patients and almost always required a long course of steroids. Infliximab allowed a reduction in the length of treatment with steroids in 2/2 cases. In conclusion, the prevalence of leprosy has decreased significantly in French Guiana, but remains driven by the population of illegal gold miners. Anti-tumour necrosis factor (anti-TNF) drugs represent a promising option in the management of reversal reactions.

P654 Controversies in the management of anti-TNF therapy in Crohn’s disease patients. A Delphi consensus

Abstract Background Over the last years significant advances have arisen in CD. New therapies with different mechanisms of action have been approved for the management of Crohn’s disease (CD). However, there is limited evidence on optimal positioning of agents as first-or second-line therapies due to the lack of head-to-head robust comparative data. Our aim was to establish feasible and practical recommendations for the management of patients with moderate to severe CD with the use of anti-tumour necrosis factor (TNF) drugs, with special focus on controversial areas. Methods A group of 9 expert gastroenterologists identified current relevant clinical controversies in the management of CD with anti-TNF therapies. A comprehensive literature review was performed to analyze them and a survey was launched to examine current clinical practice. This was a structured survey organized in 2 main sections that included several questions: 1) Sociodemographic and practice related questions; 2) Opinion and attitude in daily practice related to: the use of anti-TNFs, vedolizumab or ustekinumab in naïve and refractory patients, the role of HLA-DQA105, or monitoring of drug levels. An invitation to participate was emailed to a representative number of 244 IBD treating physicians all over the country. The results of the literature review and survey were discussed in a nominal group meeting, and a set of statements were proposed for a Delphi process. The participants of the survey were also invited to the Delphi. Agreement was defined if at least 70% of the participants voted ≥7 (from 1, totally disagree to 10, totally agree). For each statement, the level of evidence and grade of recommendation was established based on the Oxford Evidence Based Medicine categorization. Results A total of 14 statements were generated (table 1 depicts the statements and the results of the Delphi). All but two achieved required level of agreement. The statements cover the following areas: 1) use of first-line non-anti-TNF biologic therapy; 2) role of HLA-DQA1*05 in daily practice; 3) attitudes in primary nonresponse and loss of response to anti-TNF therapy due to immunogenicity; 4) ustekinumab or vedolizumab if a change of mechanism of action is considered; 5) anti-TNF drug levels monitoring during induction; 6) combined therapy with an immunomodulator and anti-TNF monotherapy. Conclusion This document sought to pull together the experts’ attitudes when dealing with different clinical scenarios of patients with CD on anti-TNF.

Vaccines in Children Exposed to Biological Agents In Utero and/or During Breastfeeding: Are They Effective and Safe?

Biological agents cross the placenta, resulting in detectable blood levels in the neonate. Neonatal vaccinations are essential to prevent serious infections. To review the effectiveness and safety of vaccines in children exposed to biological drugs in utero and/or those whose mothers received biological agents during lactation. A systematic bibliographic search was performed. Infants exposed in utero to anti-tumour necrosis factor drugs [anti-TNFs], vedolizumab or ustekinumab mount adequate serological responses to vaccines. No relevant adverse events for non-live inactivated vaccines have been reported in newborns exposed in utero to biologics. Studies assessing the safety of live-attenuated vaccines administered to infants exposed to biologics in utero have not observed, in general, serious adverse events. However, although no severe complications have been reported with rotavirus live vaccination, several fatal disseminated tuberculosis infections after administration of the BCG live vaccine in infants exposed to anti-TNFs in utero have been reported. Infliximab, adalimumab, and probably also vedolizumab and ustekinumab treatments are considered compatible with breastfeeding, although minuscule amounts of these biologics have been detected in breast milk of treated nursing mothers. Based on the literature available, the benefits from breastfeeding while receiving infliximab [or any other anti-TNF] and at the same time adhering to national infant immunization programmes probably outweigh any hypothetical risk for the infant. Vaccines appear to be effective in infants exposed to biologics in utero. Inactivated vaccines are probably safe, whereas live-attenuated vaccines should be avoided while the children have detectable levels of biological drugs. Vaccines [non-live and live] are probably safe in children breastfed by mothers treated with biologics.

Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study.

Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences. The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences. A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments. NHS inflammatory bowel disease services in the UK. Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease. We carried out a survey of health-care professionals (n = 168), qualitative interviews with health-care professionals (n = 20) and patients (n = 33), discrete choice experiments with health-care professionals (n = 116) and patients (n = 115), and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals showed that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that anti-tumour necrosis factor drugs (particularly infliximab) are the most frequently offered drugs across most steroid-resistant (and steroid-dependent) patient scenarios, but they are less frequently offered to thiopurine-naive patients. Patient interviews identified several factors influencing their treatment choices, including effectiveness of treatment, recommendations from health-care professionals, route of administration and side effects. Over time, depending on the severity and duration of symptoms and, crucially, as medical treatment options become exhausted, patients are willing to try alternative treatments and, eventually, to undergo surgery. The discrete choice experiments found that the probability of remission and of side effects strongly influences the treatment choices of both patients and health-care professionals. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. The treatments ranked most positively by patients were infliximab and tofacitinib (each preferred by 38% of patients), and the predicted probability of uptake by health-care professionals was greatest for infliximab (62%). The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation. We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis. This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 41. See the NIHR Journals Library website for further project information.

Use of biologics for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

Limited information is available on the use of biologics in patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) in Japan. The types of biologics, treatment duration, treatment prior to biologics, concomitant treatment, and characteristics of patients receiving biologics were investigated. We used a Japanese hospital claims database provided by Medical Data Vision Co. (2008-2021). In the database, 1186 of 34,207 SSc patients (3.5%) and 620 of 12,303 SSc-ILD patients (5.0%) received anti-interleukin-6 (anti-IL-6) drugs, anti-tumour necrosis factor (anti-TNF) drugs, abatacept, or rituximab. The most common were anti-IL-6 drugs [used in 35.5% of SSc patients and 38.5% of SSc-ILD patients (tocilizumab, 34.5% and 36.6%)], followed by anti-TNF drugs [31.3% and 26.5% (etanercept, 10.5% and 9.0%; others, <8%)], abatacept (17.5% and 20.6%), and rituximab (15.7% and 14.4%). Among SSc and SSc-ILD patients treated with anti-IL-6 drugs, anti-TNF drugs, or abatacept, the most common immunosuppressive drugs prior to initiation of biologics were methotrexate and tacrolimus. Approximately half of patients receiving anti-IL-6 drugs, anti-TNF drugs, or abatacept continued treatment beyond 1 year. Our study indicates that off-label biologics have been used in a certain number of SSc or SSc-ILD patients in Japan, with tocilizumab the most common.

A Role for CXCR3 Ligands as Biomarkers of Post-Operative Crohn's Disease Recurrence.

Crohn's disease [CD] recurrence following ileocolic resection [ICR] is common. We sought to identify blood-based biomarkers associated with CD recurrence. CD patients undergoing ICR were recruited across six centres. Serum samples were obtained at post-operative colonoscopy. A multiplex immunoassay was used to analyse 92 inflammation-related proteins [Olink Proteomics]. Bayesian analysis was used to identify proteins associated with increasing Rutgeerts score. Identified proteins were used in receiver operating characteristic [ROC] analysis to examine the ability to identify CD recurrence [Rutgeerts score ≥i2]. Existing single cell data were interrogated to further elucidate the role of the identified proteins. Data from 276 colonoscopies in 213 patients were available. Median time from surgery to first and second colonoscopy was 7 (interquartile range [IQR] 6-9) and 19 [IQR 16-23] months, respectively. Disease recurrence was evident at 60 [30%] first and 36 [49%] second colonoscopies. Of 14 proteins significantly associated with Rutgeerts score, the strongest signal was seen for CXCL9 and MMP1. Among patients on anti-tumour necrosis factor drugs, CXCL9 and CXCL11 were most strongly associated with Rutgeerts score. Both are CXCR3 ligands. Incorporation of identified proteins into ROC analysis improved the ability to identify disease recurrence as compared to C-reactive protein alone: area under the curve [AUC] 0.75 (95% confidence interval [CI]: 0.66-0.82] vs 0.64 [95% CI 0.56-0.72], p = 0.012. Single cell transcriptomic data provide evidence that innate immune cells are the primary source of the identified proteins. CXCR3 ligands are associated with CD recurrence following ICR. Incorporation of novel blood-based candidate biomarkers may aid in identification of CD recurrence.

Nyálkahártya pemphigoid (MMP) és terápiás lehetőségei

Mucous membrane pemphigoid (MMP) is an autoimmune subepithelial blistering disease. Oral and ocular mucosae are the most frequently afected areas, but the nasopharynx, esophagus, larynx and anogenital region can also be involved. It is characterized by linear deposition of IgG, IgA, or C3 along the basement membrane zone. In low-risk cases topical, intralesional corticosteroids are administered, together with anti-infammatory, immunomodulatory (dapsone) drugs or antibiotics (doxycycline). In severe, high-risk cases we apply systemic corticosteroids and immunosuppresive agents, or biological therapies (rituximab and anti-tumour necrosis factor drugs), or combination treatment of rituximab and intravenous immunoglobulins (IVIG)

Early detection of anti‐drug antibodies during initiation of anti‐tumour necrosis factor therapy predicts treatment discontinuation in inflammatory bowel disease

Anti-drug antibodies develop mostly during the induction therapy with anti-tumour necrosis factor (TNF) drugs and can be revealed by means of a drug-tolerant assay. To investigate whether the early detection of anti-drug antibodies during the induction therapy was predictive of treatment discontinuation. In a prospective study, consecutive patients with inflammatory bowel disease (IBD), who should start an anti-TNF, were enrolled and followed regularly during 24months or less in case of non- or loss of response (LOR) or adverse events requiring treatment discontinuation. Anti-TNF levels and anti-drug antibodies were measured at week 2 for adalimumab (ADA) and weeks 2 and 6 for infliximab (IFX) using a drug-tolerant assay. One hundred and eight patients were enrolled (54 under ADA). At week 2, antibodies to ADA and to IFX were detected in 76% and 67% of patients. Time to treatment discontinuation was significantly shorter (P<0.001) in patients with antibodies to ADA ≥2.0µg/mL-eq (6.0 vs 24months, HR=18.51, 95% CI [4.35-78.71]) or with antibodies to IFX ≥4.0µg/mL-eq (5.5 vs >24months, HR=13.89, 95% CI [4.08-47.31]) at week 2 compared to patients without positive antibodies. Antibodies to ADA and to IFX were predictive of treatment failure within 24months with a sensitivity of 79% and 62%, and specificities and positive predictive values of 100%. In multivariate analysis, antibodies to ADA or to IFX at week 2 were the only factors associated with treatment discontinuation. The prevalence of antibodies to anti-TNF is high when detected early using a drug-tolerant assay, and their appearance predicts further treatment discontinuation.

Effectiveness and safety of methotrexate monotherapy in patients with Crohn's disease refractory to anti-TNF-α: results from the ENEIDA registry.

Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited. To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs. A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI≤3 points and clinical response as HBI drop of≥3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16weeks until maximum follow up. Adverse events were recorded. Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P=0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation. The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.

What can we do to tackle anxiety and depression in patients with inflammatory bowel disease?

The mental health of patients with inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a growing concern, with data pointing not only to the high prevalence of psychiatric comorbidity1 but also to the negative effects of depression and anxiety on disease outcomes. Data consistently show that patients with IBD and comorbid mental health conditions have higher rates of surgery, diagnostic workup, hospitalisations, and corticosteroid use,2 and are less likely to adhere to anti-tumour necrosis factor drugs,3 than patients with IBD and no comorbidities.

Relationship between periodontal status and disease activity in patients with ankylosing spondylitis.

ObjectivesAnkylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints, characterized by enthesitis. Recent studies have investigated the relationship between AS and periodontitis. The aim of this study was to evaluate the periodontal status of patients with AS and to determine the factors affecting this.Material and methodsThe study included 200 AS patients, of which 129 were taking anti-tumour necrosis factor (TNF) drugs and 71 were taking non-steroid anti-inflammatory drugs (NSAID). Patients did not change their medication during the study. Disease activity was evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), mobility with the Bath Ankylosing Spondylitis Metrology Index (BASMI), functional status with the Bath Ankylosing Spondylitis Functional Index (BASFI), enthesitis with the integrated Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and quality of life with the Ankylosing Spondylitis Quality of Life (ASQoL) scale. Data related to erythrocyte sedimentation rate, and C-reactive protein were recorded from the hospital information system. The plaque index (PI), gingival index (GI), pocket depth (PD), attachment level (CAL) measurements, and bleeding index (BOP) were measured.ResultsThe results showed that 35.5% of the AS patients had periodontitis, at a lower rate in the anti-TNF group than in the NSAID group, but the difference was not statistically significant. Periodontitis-related factors were found to be age, BASFI and BASMI. A significant relationship was found between MASES and BOP and GI.ConclusionsThis suggests that periodontitis may be an enthesis in AS. Nevertheless, further studies are needed to explain the mechanism of periodontitis in AS patients.

DNA Copy Number Variation Associated with Anti-tumour Necrosis Factor Drug Response and Paradoxical Psoriasiform Reactions in Patients with Moderate-to-severe Psoriasis.

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study searched for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance of antitumour necrotic factor induced psoriasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque psoriasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packages. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to adalimumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: retrospective long-term follow-up of the LIR!C trial

The LIR!C trial showed that laparoscopic ileocaecal resection is a cost-effective treatment that has similar quality-of-life outcomes to treatment with infliximab, an anti-tumour necrosis factor (TNF) drug. We aimed to compare long-term outcomes of both interventions and identify baseline factors associated with the duration of treatment effect in each group. In this retrospective follow-up study, we collected data from patients who participated in the LIR!C trial, a multicentre randomised controlled trial that compared quality of life after surgical resection versus infliximab in adult patients with non-stricturing and immunomodulator-refractory ileocaecal Crohn's disease. From Jan 1 to May 1, 2018, we collected follow-up data from the time from enrolment in the LIR!C trial until the last visit at either the gastrointestinal surgeon or gastroenterologist. In this study, outcomes of interest were need for surgery or repeat surgery or anti-TNF therapy, duration of treatment effect, and identification of factors associated with the duration of treatment effect. Duration of treatment effect was defined as the time without need for additional Crohn's disease-related treatment (corticosteroids, immunomodulators, biologics, or surgery). We collected long-term follow-up data for 134 (94%) of 143 patients included in the LIR!C trial, of whom 69 were in the resection group and 65 were in the infliximab group. Median follow-up was 63·5 months (IQR 39·0-94·5). In the resection group, 18 (26%) of 69 patients started anti-TNF therapy and none required a second resection. 29 (42%) patients in the resection group did not require additional Crohn's disease-related medication, although 14 (48%) of these patients were given prophylactic immunomodulator therapy. In the infliximab group, 31 (48%) of 65 patients had a Crohn's disease-related resection, and the remaining 34 patients maintained, switched, or escalated their anti-TNF therapy. Duration of treatment effect was similar in both groups, with a median time without additional Crohn's disease-related treatment of 33·0 months (95% CI 15·1-50·9) in the resection group and 34·0 months (0·0-69·3) in the infliximab group (log-rank p=0·52). In both groups, therapy with an immunomodulator, in addition to the allocated treatment, was associated with duration of treatment effect (hazard ratio for resection group 0·34 [95% CI 0·16-0·69] and for infliximab group 0·49 [0·26-0·93]). These findings further support laparoscopic ileocaecal resection as a treatment option in patients with Crohn's disease with limited (affected segment ≤40 cm) and predominantly inflammatory terminal ileitis for whom conventional treatment is not successful. None.

P466 Is it possible avoid colectomy with rescue dual therapy with vedolizumab plus tacrolimus in ulcerative colitis that losing response to anti-tumour necrosis factor?

Abstract Background There is an increasing number of ulcerative colitis (UC) patients that losing response to anti-tumour necrosis factor (TNF) drugs. There is low evidence about combining Tacrolimus (TAC) with vedolizumab (VED) for UC patients, who have failed treatment with anti-TNF therapy. The aim of the present study was to assess the efficacy and safety of TAC with VED in UC patient refractory to anti-TNF therapies. Methods Inclusion criteria: patients with moderately to severely active UC and who failed or showed intolerance to at least one TNF antagonists that received dual therapy with VED and oral TAC (Envarsus®). TAC blood levels were monitored at weeks 2,4,8 and then every 2 months. Rates of clinical response and remission were evaluated in November 2019 using the Mayo score. Clinical response was considered when PCR and calprotectin were decreased ³50% and biological remission was considered when PCR and calprotectin achieved normal values. Results Seven UC patients (1 proctitis, 3 left colon disease, 2 Pancolitis and 1 pouchitis) had sufficient dTNF for analysis. Demographic dTNF: age 51 ± years and 10.4 ± years since UC was diagnosed. All patients received thiopurine therapy and 86% received corticosteroids. 43% of patients were corticodependent and 43% were corticosteroid-refractory. 29% of patients failed to one TNF antagonists and 71% of patients failed to two TNF antagonists. Previous to started dual therapy; 29% of patients with moderate endoscopic activity and 71% of patients with severe endoscopic activity. Thiopurine treatment was suspended and 3 corticosteroid-refractory patients received IV cyclosporine therapy. The median dual therapy follow-up was 12.8 months (range 6–30 months). At the end of the study period; all patients presented clinical response, 86% of patients were corticosteroids free and biological remission was achieved in 71% of patients and any patient required colectomy. Fifty-seven per cent of patients needed VED dose intensification. Side effects were mild; abdominal pain (1), tremor (4), hypertension (1), moderate decrease creatinine clearance (1), insomnia (1) and arthralgías (1). Any patient discontinued dual therapy by adverse drug effect. At the end of the study, 4 patients continued with the dual therapy and 3 patients TAC was discontinued due to maintained clinical remission Conclusion In UC patients that losing response to anti-tumour necrosis factor (TNF) drugs and corticosteroid-refractory, the dual therapy with VED plus TAC could be an alternative, effective and safe therapy.