bluuebunny/crossref_metadata_2025_split huggingface dataset:
P572 Therapy optimisation and intravenous ferric carboxymaltose in active or inactive IBD with iron deficiency: it’s time to make iron deficiency part of tight monitoring to reach T2T? – preliminary results of a prospective study
Authors: Molnár T , Resál T , Bacsur P , Rutka M , Szántó K , Bálint A , Milassin Á , Fábián A , Bor R , Szepes Z , Farkas K 
Published: January 2022

Abstract

Background
Iron deficiency (ID) is often a neglected condition in inflammatory bowel disease (IBD), even though it is one of the most common extraintestinal manifestation. Our questions were the follows: If iron deficiency is part of the T2T management as CRP or fecal calprotectin and requires optimisation of the current therapy, how does this affect the medium-term outcome of the disease and the effectiveness of IV iron replacement? If the disease is active, does optimisation of therapy is sufficient to manage iron deficiency or iv. iron supplementation is also necessary?

Methods
Patients with ID defined by the ECCO guideline (Figure 1.) were randomly included in our prospective one-center, four arms study. Patients were divided into an active (A) and a remission (R) group. Activity was defined by CRP ≥10 mg/l or clinical activity scores CDAI ≥150, pMayo ≥3. Therapy optimisation was performed in the active group, further randomisation was performed into two subgroups: therapy modification alone (A1) or modification with iv. ferric-carboxymaltose (A2). All patients received iron supplementation in the remission group with (R2 – iron T2T group) or without therapy optimisation (R2). Every two months laboratory parameters and clinical activities were assessed until 6 months.

Results
65 patients were included (CD 83.4%). Average follow-up was 3.9 months. Number of patients per group: A1:17, A2:23, R1:16, R2:9. Based on our results, iv. iron supplementation with modification in treatment was more efficient, than therapy optimisation alone, as the difference in increase in haemoglobin (p&lt;0.001), haematocrit (p&lt;0.001) and ferritin (p&lt;0.05) was significant after 2 and 4 months the enrollment. In the remission group iv. iron supplementation with therapy optimisation was more effective, than iv. iron alone, based on transferrin saturation (p&lt;0.05), serum iron (p&lt;0.05) and CRP (p&lt;0.05) during the 2 months period. After that period, no further significant difference was measured. Iv. iron seems to be equally effective both in the active and in the remission group, as no significant difference was measured during the 6-month period. No adverse event was observed.

Conclusion
Our results suggest, that therapy optimisation in addition to iron replacement is more effective in patients with remission and therefore biomarkers of IDA should be involved in the thight monitoring algorhytm to react T2T. However, therapy optimisation has to be associated with iv iron replacement in IBD with IDA and activity without the risk of worsening disease activity. Based on our results, ferric-carboximaltose is an effective and safe therapeutic method in the treatment of IDA associated with active or inactive IBD.
P575 Safety and efficacy of autologous haematopoietic stem cell transplantation for refractory Crohn’s disease after cyclophosphamide-free mobilisation: Preliminary Results
Authors: Giordano A , Rovira M , Barastegui R , Marín P , Martínez N , Fernández-Aviles F , Suárez-Lledó M , Doménech A , Ordás I , Fernández-Clotet A , Caballol B , Gallego M , Vara A , Masamunt M C , Giner A , Corraliza A M , Panés J , Salas A , Ricart E 
Published: January 2022

Abstract

Background
Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with refractory Crohn’s disease [CD]. Although the safety of the procedure has been improved over the last decade, AHSCT is still burdened by high adverse event rate due to chemotherapy toxicity and immunosuppression. The aim of this study was to evaluate the safety and efficacy of AHSCT by using a cyclophosphamide (Cy)-free mobilisation regimen followed by a standard conditioning approach.

Methods
A prospective observational study was conducted at Hospital Clínic of Barcelona in refractory CD patients undergoing AHSCT. Outpatient regimen with G-CSF 12–16 μg/kg/daily for 5 days was used for mobilisation. Patients who failed to achieve &gt;2x106 CD34+ cells received Plerixafor 240 μg/d (1–2 doses). For conditioning, Cy and ATG were administered according to standard protocols. After transplant, patients were followed-up at regular intervals. Colonoscopy and/or magnetic resonance imaging were performed at baseline and at weeks 26, 52, 104 after AHSCT. Crohn’s Disease Activity Index (CDAI) and SES-CD were used for clinical and endoscopic disease assessment.

Results
From June 2017 to October 2021, 14 refractory CD patients were enrolled (9F, median age 40 yr, median CDAI 204, median SES-CD 13); all of them achieved successful mobilisation (median collected CD34+ cells 7.7x106±2.8) and were transplanted. Patients were followed-up during a median of 71.5 months [0–104]. No SAEs or CD worsening were observed during mobilisation. The proportion of patients in clinical remission (CDAI&lt;150) was 70% at 6 months, 43% at 1 yr and 60% at 2 yr. Median SES-CD was 3 at 6 months and 9 at 1 yr. The proportion of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 0% at 6 months, 30% at 1 yr and 40% at 2 yrs. AEs and SAEs during and after conditioning were comparable to previous series, being neutropenic fever the most frequently observed (54%). Colectomy due to refractory severe relapse was needed in one patient at 70 weeks from transplant.

Conclusion
Cy-free mobilisation is feasible and safe in refractory CD patients undergoing AHSCT but early relapse is observed in a significant proportion of patients. While representing an improvement on safety, studies exploring early reintroduction of drugs to decrease relapse rate after transplant are warranted.
P578 Non-medical switch between adalimumab biosimilars and from the originator adalimumab to biosimilars in inflammatory bowel disease patients – a multicentre study on efficacy and drug sustainability
Authors: Lontai L , Gonczi L , Balogh F , Komlodi N , Resal T , Farkas K , Molnar T , Golovics P , Schafer E , Szamosi T , Miheller P , Ilias A , Lakatos P L 
Published: January 2022

Abstract

Background
The use of biosimilar adalimumab (ADA) is effective and safe in inflammatory bowel disease (IBD), although clinical data on switching between ADA biosimilars is still rare. At the end of 2020, a non-medical switch to biosimilar ADA became mandatory in Hungary due to reimbursement policy changes of the National Health Insurance Fund of Hungary (NEAK). The aim of the present study was to evaluate short- and medium term clinical efficacy, drug sustainability and safety comparing non-medical switches from the originator to biosimilar ADA, and between ADA biosimilars.

Methods
246 consecutive patients on maintenance ADA therapy (n=181 Crohn’s disease [CD] and n=65 ulcerative colitis [UC], male/female: 44%/56%, median disease duration: 10years(y) (IQR: 10–16)) were included from 4 IBD centers between September 2019 and December 2020. Data on clinical efficacy, using Crohn’s Disease Activity Index (CDAI) and partial Mayo Score (pMayo), laboratory parameters (C-reactive protein – CRP) and adverse events were collected at 8–12 weeks prior switch, at baseline, and 8–12 weeks, 20–24 weeks after switch. Drug sustainability following the switch was evaluated after a median of 41 weeks (IQR: 35–42) follow-up time.

Results
A total of 246 IBD patients (n=153 patients [115CD/38UC, median age: 38y(IQR: 27–45)] and n=93 patients [66CD/27UC, 32y(IQR: 26–40.5)] underwent a non-medical switch from the originator to a biosimilar, and biosimilar to biosimilar. Clinical disease activity based on CDAI and pMayo scores are presented in Figures 1 and 2. No significant difference was found in the proportion of patients in clinical remission at week 8–12 prior switch / switch / week 8–12 and week 20–24 in either patients switched from originator to biosimilar (86.8% / 88.2% / 86.0% / 85.0%; p=0.87 among groups) or biosimilar to biosimilar (72.0% / 77.4% / 84.9% / 77.6%; p=0.21). 89.2% and 83.1% of patients who were in clinical remission at switch/baseline sustained clinical remission up to week 20–24 in the first and second cohorts. Mean CRP levels were also unchanged during follow-up in both cohorts (p=0.71 and p=0.94). Drug survival was similar between originator to biosimilar and biosimilar to biosimilar switch cohorts, with a probability of 90.6% (SE: 2.4) and 85.8% (SE:3.7) to stay on drug after 40 weeks (log-rank: p=0.271). Figure 3. Two cases of skin reactions were registered as adverse events, one leading to treatment discontinuation.

Conclusion
Clinical remission was sustained following non-medical switch from originator or biosimilar adalimumab to a biosimilar in IBD patients. Medium-term drug sustainability following the switch was high, and comparable between patients with an originator to biosimilar and a biosimilar to biosimilar switch.
P582 Association between serum ustekinumab concentrations and endoscopic disease activity in Crohn’s disease
Authors: Yanofsky R , Abduallah Y , Golovics P , Lakatos P L , Bitton A , Wild G , Afif W , Bessissow T 
Published: January 2022

Abstract

Background
Therapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown. The primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR).

Methods
Adult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2019 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis.

Results
53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (Figure 1. ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively).

Conclusion
There was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings.
P593 Biologicals and small molecule combotherapies: promising experience in refractory IBD patients
Authors: Juillerat P , Martinho-Grueber M , Michetti P 
Published: January 2022

Abstract

Background
It has been hypothesized that combination of two biologics or with a small molecule could ”break the ceiling” of the efficacy (~60%) of currently available biological therapies for IBD patients. The best combinations and their safety are, however, unknown.

Methods
A chart review of Inselspital, Bern University hospital und Crohn and colitis center Beaulieu Lausanne, of IBD patients on combination therapy have been performed. Data on disease phenotype, previous treatment and efficacy and safety of the new combinations have been collected and studied to help moving forward the use of this armentarium.

Results
Among 18 identified IBD patients (39% women, 10 ulcerative colitis, 8 Crohn’s disease) with extended and refractiry luminal disease (indication) who received 21 combination therapies between June 2017 and November 2021. They suffered from steroid-dependency and half of them were refractory to at least two anti-TNF alpha agents. These treatments have been started after a median duration of disease of 6 years (range 1–25) for a mean period of combo treatment of 11 months (range 1–52), 8 were still ongoing. Various combotherapies and clinical response (arrows; red=bad, green=good response) are presented in Figure 1. A partial or complete response was observed in 15/21 therapies (71%) with a mean decrease of CRP of 11 mg/l (range+23 to -59) and calprotectin of 399 mcg/g (range 0 – 1745) among the reponders. Concerning safety, 2 infections (otitis media, skin mycosis), 1 non hodgkin Lymphoma and 4 minor adverse events (tumefaction left parotide, eczema, 2x lymphopenia) have been reported, mostly when small molecules have been involved.

Conclusion
Ustekinumab combined with anti-TNF agents in Crohn’s disease is more effective than vedolizumab and tofactinib in ulcerative colitis. Combining with small molecules increases the risk of lymphopenia, of cancer (1 case of non hodgkin lymphoma) and minor infections in severe refractory and steroid-dependent inflammatory bowel disease patients.
P597 Bone mineral density in patients after total proctocolectomy and pouch surgery due to Ulcerative Colitis have low bone mineral density, and low performance of DXA scans- a cross sectional study
Authors: Pfeffer-Gik T , Godny L , Ollech J , Wasserberg N , Barkan R , White I , Yackobovitch Gavan M , Kraizler M , Yanai H , Dotan I 
Published: January 2022

Abstract

Background
The reported prevalence of low bone mineral density (BMD) in patients with inflammatory bowel diseases (IBD) varies between 20–50%. The multiple contributing factors include inflammation,use of corticosteroids, life style and diet.Patients with ulcerative colitis (UC) undergoing proctocolectomy with ilealpouch-anal anastomosis (IPAA) commonly develop pouchitis-de novo inflammation in previously normal small bowel, which may resemble Crohn’s disease (CD).
We aimed to assess rate of low BMD in patients with a pouch and rate of DXA performance.

Methods
Patients after IPAA due to UC were prospectively followed; Questionnaires regarding demographic, disease course, surgery, diet and blood tests were collected biannually.
BMD was assessed by dual-energy x-ray absorptiometry(DXA).All medical records were reviewed for DXA performance within the last five years, if not found-patients were contacted and submitted the results. Low BMD was defined as T score &lt; -1.

Results
Out of 146 prospectively followed patients, data regarding DXA was available for 114; 70 (61%) women. Median age 46 (IQR 38–67), median age at UC diagnosis 21 years (IQR 15.7–29.5), median pouch age 16 years (IQR 8.5–22.5). DXA scans were performed in 41/114 patients (36%), low BMD was noted in 68.3 %: osteopenia- 16 (39%), osteoporosis: 12 (29.3%). Patients performing DXA scan were older: 54 (IQR 42–64) vs. 45 years (IQR 31–54) (p=0.012), and were diagnosed with UC at younger age: 23 (IQR 17–29) vs. 19 years (IQR 14–26) (p=0.018). Smoking, UC duration prior to IPAA, indication for surgery, pouch age and pouchitis were comparable between patients who performed and did not perform DXA scans. In patients with low BMD- current smoking rates were higher compared to those with normal BMD:4 (14.3%) vs. 0 (p=0.008),respectively. Vitamin D levels in patients with low and normal BMD were comparable:22.8 (IQR 17.5–26) vs. 20 (IQR 16.8–21.8)ng/ml (p=0.158), respectively. Vitamin D supplementation was comparable as well [38% vs. 60% (p=0.16)]. No differences in micronutrients consumption between the groups were noticed.

Conclusion
In a prospective cohort of patients after IPAA due to UC, approximately 36% performed DXA scans and the majority of them had low BMD, with smoking as a potential risk modifier. Due to high rates of low BMD in this population multidisciplinary advice and follow up should be provided to address the low performance of DXA scans and the abnormalities in BMD.
P612 Mirikizumab Pharmacokinetics and Exposure - Efficacy Relationships in Patients with Ulcerative Colitis
Authors: Friedrich S , Chua L , Tuttle J L , Feagan B G , Sandborn W J 
Published: January 2022

Abstract

Background
Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy in a Phase 2 trial in patients with moderately-to-severely active ulcerative colitis (UC)1 (NCT02589665). Analyses of the pharmacokinetics (PK) of miri and the relationships between exposure and efficacy at Week 12 are reported.

Methods
Patients were randomised to receive IV placebo, miri 50 mg or 200 mg with possibility of exposure-based dose increases, or miri 600 mg every 4 weeks, with efficacy assessment at Week 12. Serum concentrations of miri were analyzed using population PK methods. Population models were also used to evaluate the relationships between various clinical efficacy measures at Week 12 and miri exposure. The effects of patient factors on both PK and exposure-efficacy relationships were evaluated. Model-based and graphical methods were also used to understand the potential for confounded relationships between miri exposure and efficacy.

Results
A systemic clearance of 0.023 L/hr was estimated for miri, similar to estimates in healthy subjects and patients with psoriasis. Miri exposure increased in a linear manner. Patients with lower serum albumin concentration or lower body weight tended to have significantly higher clearance or lower volume of distribution, respectively (p&lt;0.01); however, the magnitude of the impact was small and contributed less than 15% to random variability. The model-based exposure-response analyses generally showed that patient factors had a stronger impact on efficacy at Week 12 than miri exposure. Prior biologic experience and baseline rectal bleeding (RB) score had significant impacts (p&lt;0.01) on the estimated placebo effect and maximal miri treatment effect (Emax), respectively. In the clinical response model, the estimated placebo response rate was 20 percentage points higher in biologic naïve vs experienced patients. The estimated response rate at a miri dose of 600mg was 28% higher in patients with a baseline RB≥2. Inclusion of these factors in the exposure-efficacy models caused the estimated EC50 to drop substantially, suggesting that the post-hoc exposure-efficacy relationships are likely confounded based on these patient factors. Graphical evaluations also suggested the presence of confounding factors.

Conclusion
Miri PK in UC patients was consistent with PK observed in healthy subjects and psoriasis patients. Evaluation of the relationships between miri exposure and efficacy in UC patients accounted for the potential impact of patient factors. Confounding patient factors may distort the true cause-effect relationship between exposure and efficacy and were carefully considered in support of optimal selection of doses for miri Phase 3 studies.

Reference
1. Gastroenterology. 2020;158(3):537–549.
P619 Patterns of Anti-TNF Prescribing & Therapy Outcome in a Large Multicentre Cohort of Inflammatory Bowel Disease Patients
Authors: Doherty J , Stack R , O Morain N , Coe C , Corcoran R , Ryan B , Doherty G , Mc Namara D , Kevans D 
Published: January 2022

Abstract

Background
Anti-TNF agents are effective therapies for Inflammatory Bowel Disease (IBD), however, a significant proportion of patients lose response over time. Real world data on prescribing practices and outcome of anti-TNF therapy are of utility to practicing clinicians

Methods
To evaluate Anti-TNF prescribing practice and durability of Anti-TNF response in a large multicentre IBD cohort. IBD patients commencing an anti-TNF agent, as first biologic therapy, at participating academic centres were identified from institutional databases. Baseline demographic data, concomitant medication and biologic therapy history were collected. Adalimumab(ADA) and Golimumab(GOL) were consider subcutaneous(SC) anti-TNF agents. Date of commencement and discontinuation of first and second line anti-TNF therapy was documented. Kaplan-Meier survival curves were constructed for time based analyses. P values less than 0.05 were considered significant in all analyses.

Results
N=991 patients with IBD were included in the study. 29%, 69% and 2% had UC, CD and IBD-U respectively; median [IQR] age 27 [19–37] years; 50% female. 31%, 63% and 4% received infliximab(IFX), ADA and GOL respectively as first-line anti-TNF therapy. 35% of patients received an immunomodulator in combination with first-line anti-TNF agent. Median [95% CI] survival free of therapy discontinuation for first and second-line anti-TNF agents was 4.6 [3.7 – 5.3] years and 3.0 [2.1 – 3.9] years respectively. Survival free of anti-TNF discontinuation was significantly shorter for IFX monotherapy group compared with IFX combination therapy, SC anti-TNF monotherapy and SC anti-TNF combination therapy groups, p=0.005.

Conclusion
While anti-TNF therapies are effective a significant proportion of patients discontinue therapy over time. Second line anti-TNF therapy results in a less durable response with a shorter time to drug discontinuation compared with first line anti-TNF therapy. The use of a combination immunomodulator is particularly important with infliximab therapy, however, does not influence durability of response for subcutaneous anti-TNF agents.