Explore the vast range of titles available.

BackgroundCombination therapy with immunomodulators and anti-TNFs were recommended following the results of the SONIC study. It was determined the main benefit for combination therapy was due to reduction in the risk of anti-drug antibodies. The PANTS study indicated that patients at higher risk of antidrug antibodies to anti-TNF agents could be identified with HLADQA1*05 allele carriage. A HLADQA1*05 stratified withdrawal of immunomodulators has not been evaluated before.MethodsWe included IBD patients on combination immunomodulaotrs and anti TNF agents from a prospective database who had HLADQA1 *05 status determined retrospectively after treatment of minimum 12 months. Patients with Crohn`s disease -perianal fistula or those on immunomodulators due to non-IBD indications were excluded. Immunomodulator withdrawal was offered to all patients in clinical and biomarker remission with a negative HLADQA1805 status. Patients were followed up with structured clinical and biomarker assessment. Therapeutic drug monitoring was performed at 3–6 month intervals. The primary outcome was development of anti-drug antibodies.ResultsThree hundred and eighteen patients on anti-TNF agents had HLA-DQA1*status determined. Among these 248 patients were on combination therapy. Withdrawal of immunomodulaotrs was suggested to 146 (59%) of the HLA-DQA1*05 negative patients. None of the patients declined attempt at withdrawal but five patients preferred dose reduction rather than complete cessation and these were not included in analysis. Median follow up among the remaining 141 patients was 13 months (range 3–27 months). Antidrug antibodies developed in 11 patients (7.8%) including in three patients with undetectable drug levels necessitating switch of agent. An additional 16 patients lost clinical response without development of antibodies.ConclusionIn anti TNF treated IBD patients in long-term remission, withdrawal of immunomodulators is feasible in majority of patients not carrying HLA-DQA1*05 with limited risk of development of antidrug antibodies.

IntroductionThe PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available.AimTo evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomesMethodsWe prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at 6 and 12 months. Secondary outcomes were steroid free remission at 6 and 12 months, use concomitant immunosuppression and proportion needing dose escalation.ResultsSeventy-six patients were included in analysis (UC= 32, CD=43, IBD-U =1). HLADQA1*05 was positive in 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in 44% of the whole cohort and in 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in 8 patients and secondary loss of response in 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in 10 (15.6%) patients with 7 out of 10 positive for HLADQA1*05. However, only 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at 6 months was recorded in 77.1% and 78% respectively. There was no significant difference in drug persistence rates at 6 months and 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure 2). Steroid free remission at 6 and 12 months was also similar irrespective of the variant status (Figure 3)Abstract PMO-41 Figure 1Initial Theraphy choiceAbstract PMO-41 Figure 2Treatment presistance with initial theraphy strategyAbstract PMO-41 Figure 3Steroid free remissionConclusionsChoice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.

IntroductionThe efficacy of ustekinumab in prior biologic exposed refractory patients with inflammatory bowel disease is significantly inferior to those who are bio naïve. The optimal therapeutic level and hence the optimal dosing strategy in this setting is uncertain. Whether early dose optimisation is beneficial in this group of patients has not been evaluated. We aimed to compare the effectiveness and safety of early dose optimisation for maintenance compared to conventional maintenance regime in a retrospective cohort of refractory IBD patients.MethodsAll patients initiated on ustekinumab following failure of one or more anti-TNF agents were included. Patients who received conventional maintenance regime (Q8W) was compared to those who received accelerated maintenance regime (Q4H). The primary end point was steroid free remission at 12 months or at last follow up. The secondary end points were ustekinumab persistence at 6 months and 12 months, need for surgery and drug related infectious or non-infectious complications.ResultsOne hundred and four patients were included (male: female 48:56). Median follow up was 11 months (IQR 5-14). Fifty-six patients received accelerated dosing regimen while 48 patients received standard dosing regime. Dose escalation was required in 18 patients (37.5%) of standard dosing regimen while four patients (7.1%) in the accelerated dosing regimen had dose de-escalation. Higher proportion patients in the accelerated dosing regimen were in steroid free remission 87.5% vs 68.8% (p=0.018). Proportion of patients requiring surgery was higher in the standard dosing regimen group (22.91 5 vs 7.14%, p = 0.02). Ustekinumab persistence in patient started on the accelerated regime and conventional dosing regime was not significantly different at 6 months (94.1% and 95.3%, p=0.58) and 12 months (84.4% and 95.3, p=0.1). No serious drug related complications observed in either group.ConclusionsEarly dose optimisation of Ustekinumab improves steroid free remission rates and reduces the need for surgery in patients with anti-TNF refractory patients with IBD.

The impact of COVID-19 on inflammatory bowel disease (IBD) patients under pharmacological immunosuppression is still not clearly understood. We investigated the incidence of COVID-19 and the impact of immunosuppression and containment measures on the risk of SARS-CoV-2 infection in a large IBD cohort, from a multicenter cohort from 21st of February to 30th of June, 2020. Ninety-seven patients with IBD (43 UC, 53 CD, one unclassified IBD) and concomitant COVID-19 over a total of 23,879 patients with IBD were enrolled in the study. The cumulative incidence of SARS-CoV-2 infection in patients with IBD vs. the general population was 0.406% and 0.402% cases, respectively. Twenty-three patients (24%) were hospitalized, 21 (22%) had pneumonia, four (4%) were admitted to the Intensive Care Unit, and one patient died. Lethality in our cohort was 1% compared to 9% in the general population. At multivariable analysis, age > 65 years was associated with increased risk of pneumonia and hospitalization (OR 11.6, 95% CI 2.18–62.60; OR 5.1, 95% CI 1.10–23.86, respectively), treatment with corticosteroids increased the risk of hospitalization (OR 7.6, 95% CI 1.48–40.05), whereas monoclonal antibodies were associated with reduced risk of pneumonia and hospitalization (OR 0.1, 95% CI 0.04–0.52; OR 0.3, 95% CI 0.10–0.90, respectively). The risk of COVID-19 in patients with IBD is similar to the general population. National lockdown was effective in preventing infection in our cohort. Advanced age and treatment with corticosteroids impacted negatively on the outcome of COVID-19, whereas monoclonal antibodies did not seem to have a detrimental effect.

IntroductionAcute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts.AimsWe used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways.MethodsAdults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019–1 June 2019 and 1 March 2020–30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids.Results37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission.ConclusionsIn a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed.Trial registration number NCT04411784.

IntroductionMetastatic Crohn’s disease (MCD), also known as cutaneous Crohn’s disease is one of the rarest cutaneous lesions in IBD. It is defined by granulomatous lesions infiltrating the skin that are discontinuous from the affected GI tract. In most occasions, MCD occurs parallel to the course of a well-establish GI disease, but occasionally it can precede the GI manifestations from months to years. Studies addressing the therapeutic approach to MCD are limited. Ustekinumab is licenced for Crohn`s disease and also for skin disorders including psoriasis. We report our experience in managing MCD in a tertiary IBD centreMethodsThis is a single centre retrospective review of biopsy proven cutaneous Crohn’s disease. Patient details obtained from patient records included demographic data, previous failure to biologics and/or IMS, response and time to response to Ustekinumab and therapeutic drug monitoring.ResultsA retrospective review of patients with cutaneous Crohn’s disease was performed. All patients had undergone a skin biopsy for histologically confirmation. Ten patients were included (Males: Females 5:5). Median age was 53 years (IQR 24–67). The most common location was the perianal area often preceded by a surgical wound from a proctectomy and 2 patients had peristomal skin affected. Ninety- percent of patients had failed antiTNF therapy and 6 out of 10 had failed to both Infliximab and Adalimumab, one of them had also lost response to Vedolizumab. All patients received ustekinumab with median follow up since initiation of 45 months (IQR 27–60). All patients noticed improvement since initiation of Ustekinumab with a median time to response of 10 weeks (IQR 4–28). Four out of 10 patients achieved a complete healing of the skin lesions (see example picture shared with patient’s consent) while rest of patients reported a partial response. Most patients had therapeutic or supratherapeutic Ustekinumab level ranging from 2 to 6 mg/L. Dose escalation was done in 8 patients.Abstract P68 Figure 1ConclusionsMetastatic Crohn’s disease is a rather uncommon entity with different clinical manifestations. Our series report satisfactory response to ustekinumab in MCD. Larger studies are required to confirm these findings.

IntroductionCombination therapy using thiopurines or methotrexate is recommended to reduce the risk of immunogenicity in IBD patients treated with anti TNF agents. The PANTS study reported the association of HLA DQA1*05 carriage with development of anti-drug antibodies to anti TNFs in patients with Crohn`s disease. Since 2020, we have incorporated determination of HLA status in the pre-biologic screening of IBD patients. We aimed to evaluate persistence at 6 and 12 months in patients stratified to receive mono or combo therapy with anti TNFsMethodsA prospective database of all IBD patients starting biologics was interrogated to select patients initiating on anti TNF agents. We excluded patients Crohn`s disease perianal fistula who had specific indication for combo therapy, patients with acute severe UC receiving accelerated induction those who were already on imunomodulators prior to initiation of anti TNF agents. Data was collected on demographics, disease characteristics, HLA DQA1*05 status, drugs levels and antidrug antibody status at week 6, week 14 and at least one time point during a 1 year maintenance period. The primary outcome was drug persistence at 12 months.ResultsOne hundred and fifty six patients were initiated on anti TNFs during the study period. HLA DQA1*05 was positive in 59 (37.8%) of patients. These patients received combination therapy (Infliximab + thiopurines in 42, Infliximab plus methotrexate in 9, adalimumab plus azathioprine 6, Adalimumab plus methotrexate in 2). All patients negative for HLADQA1805 received monotherapy with infliximab (78) or adalimumab (19). Primary non response was identified in 30 patients (overall 19%, Monotherapy 17(17.5%), combo therapy 13 (22% ) and were switched to a non anti TNF agent Further 9% of patients had dose escalation due to suboptimal drug levels and partial response among whom 6 patients were switched to another class. Eleven patients stopped anti TNFs (4 and 7 in mono and combo therapy group respectively) due to intolerance and five patients discontinued immunomodulators in the combo therapy due to adverse effects.Anti-drug antibodies was detected at week 6 in 2 patients in the monotherapy group and 3 patients in combo therapy group (p=NS). There was no difference in rates of antidrug antibody development during maintenance period between the two groups. One hundred and twelve patients remained on anti TNFs across both groups at 12 months follow up. The overall drug persistence rates was similar in the mono and combination therapy group (66.1% vs 72.2%, p=NS).ConclusionsHLA DQA1*05 status incorporated anti TNF treatment strategy may alleviate the need for combination therapy in IBD patients with no impact on development of anti-drug antibodies and drug persistence. A biomarker stratified randomised trial is recommended.