P537 Early predictors of long term clinical response to adalimumab in Crohn's disease

Abstract Background Anti-TNF antibodies treatments are the only first-line reimbursed biologics for Crohn’s disease (CD) in several countries. Recently, Vedolizumab (VDZ) and Ustekinumab (UST) were added to the therapeutic armamentarium for CD refractory to a first anti-TNF antibody. However, studies comparing these two compounds remain unavailable. Our aim was to compare their efficacy in second-line treatment in CD after failure of one TNF antagonist. Methods All patients with CD refractory (primary or secondary non-responders) to first anti-TNF treatment and receiving UST or VDZ as a second biologic were included retrospectively in 10 French tertiary centres. The remission and clinical response were assessed at week 14. On the long-term, the cumulative probabilities of being in remission were estimated using the Kaplan–Meier method and the associated factors using a Cox proportional risk model. The drug survival to assess efficacy as well as side effects was assessed by actuarial analysis. Results 88 patients were included, 50 (57%) females (mean age: 41 ± 15 years), 61 (69%) being treated with UST and 27 (31%) with VDZ. The first anti-TNF was discontinued for primary or secondary non-response in 66 (75%) patients and for side effects in 22 (25%) patients, without any difference between the anti-TNF antibody previously used. Among the 55 patients with endoscopic data at baseline, 55 (98%) had ulceration, a CRP above 5mg/l for 33/71 (46%) patients and a faecal calprotectin > 250 µg/g for the 12 patients tested. At week 14, no difference was observed for clinical response and clinical remission according to the type of treatment: the rate of clinical response and remission were 74% (UST)/58% (VDZ) (p = 0.20) and 33% (UST)/26% (VDZ) (p = 0.56), respectively. The only factor associated with short-term remission was the lack of optimisation prior to anti-TNF discontinuation (p = 0.038) regardless of the type of second-line therapy (UST, p = 0.02; VDZ, p = 0.03). After a mean follow-up of 67 weeks, the cumulative probabilities of being in remission at 6 and 12 months were 16% and 34% for UST and 25% and 44% for VDZ, respectively (p = 0.24 for UST vs. VDZ). The drug survival was higher in the UST group as compared with the VDZ group (HR (UST vs. VDZ) = 2.36 [1.02–5.5], p = 0.04). Conclusion Our preliminary results suggest that VDZ and UST have similar efficacy in the short- and long-term response when used as a second-line biologic therapy in CD refractory to a first anti-TNF antibody. These results will be complemented for the congress by the inclusion of additional patients recruited into this registry.

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Long-Term Response Rates to Infliximab Therapy for Crohn’s Disease in an Outpatient Cohort

Canadian Journal of Gastroenterology ◽

10.1155/2009/180840 ◽

2009 ◽

Vol 23 (5) ◽

pp. 348-352 ◽

Cited By ~ 25

Author(s):

Christopher W Teshima ◽

Adrienne Thompson ◽

LeRose Dhanoa ◽

Levinus A Dieleman ◽

Richard N Fedorak

Keyword(s):

Crohn’S Disease ◽

Clinical Practice ◽

Crohn's Disease ◽

Clinical Response ◽

Clinical Outcomes ◽

Safety Data ◽

Real Life ◽

Response Rates ◽

Infliximab Therapy

BACKGROUND: Infliximab’s efficacy in the induction and maintenance of remission in luminal Crohn’s disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes.OBJECTIVE: To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic.METHODS: A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease.RESULTS: One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection.CONCLUSION: Patients treated with infliximab therapy for luminal Crohn’s disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.

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P636 Changes in peripheral helper T-cell was associated with sustained response to a 12-week EEN therapy in active Crohn’s disease: A pilot study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.764 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S528-S529

Author(s):

K Guo ◽

W Gong ◽

T Zheng ◽

W Li ◽

M Fang ◽

...

Keyword(s):

Crohn’S Disease ◽

T Cell ◽

Crohn's Disease ◽

Clinical Response ◽

Treg Cell ◽

Mucosal Healing ◽

Sustained Response ◽

Helper T Cell ◽

Early Increase

Abstract Background Exclusive enteral nutrition (EEN) is an effective solution in inducing remission in patients with active Crohn’s disease (CD). However, the underlying mechanism is not completely clear. Evidence is accumulating that potential beneficial in regulating the inflammatory immune response of CD, a chronic inflammation dominated by pathogenic TH1 and TH17 cells. We investigated the relationship between changes of circulating helper T cell and clinical response in CD during treatment with EEN. Methods Sixty-eight adults with active CD treated successfully with EEN were prospectively study. Peripheral helper T cell (Th1, Th2, Th17 and Treg) were evaluated using flow cytometry from baseline to Weeks 4 and 12. We also determine the prognostic value of the ratio of delta Th cell at Weeks 4 to baseline (△Th w4-w0) in patients receiving EEN. Mucosal healing was assessed with endoscopy at baseline and Week 12. Results Treatment with EEN significantly improved disease activity scores and laboratory biochemical markers measured at Weeks 4 and 12 compared with baseline (p < 0.05 and p < 0.001). After the initiate of EEN, we observe early modulating effects of EEN on helper T-cell percentages, especially in Treg cell. Furthermore, we found a long-term increase in Treg cell percentages in patients who sustained response to EEN during follow-up. Mean increases of Treg cell from baseline in patients sustained response were significantly larger in a patient who loss of response (p < 0.01). Receiver operating characteristic (ROC) analysis to predict sustained response at 12 weeks showed area under the curve (95% confidence interval) of Treg cell at 4 weeks (Treg w4) and change in Treg cell from baseline to 4 weeks (△Treg w4-w0) to be 0.75 (0.56–0.87) and 0.84 (0.63–0.92), respectively. Logistic regression analysis confirmed that △Treg w4-w0 (31.8%) after the EEN was significant independent predictive factors for sustained response. Mucosal healing at Week 12 was achieved by 97.1% of patients who long-term increase of Treg cell compared with 51.5% of those temporary raise (p < 0.001). Conclusion EEN resulted in rapid improvements in laboratory markers and early increase in Th subsets percentages. Early increase of Treg cell predicts a sustained response to EEN and mucosal healing. Monitoring of Treg cell may help predicts the sustained clinical response and course.

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P419 Clinical effectiveness and safety of first-line biologic vedolizumab as a monotherapy or combination therapy in ulcerative colitis and Crohn’s disease patients: results from the EVOLVE study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.548 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S381-S382

Author(s):

B Bressler ◽

A Yarur ◽

U Kopylov ◽

M Bassel ◽

N Brett ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

Clinical Effectiveness ◽

First Line ◽

Safety Outcomes

Abstract Background There is little long-term research (≥12 months) in ulcerative colitis (UC) and Crohn’s disease (CD) patients investigating the impact on clinical effectiveness of combined (combo) therapy of vedolizumab (VDZ) plus immunomodulators/immunosuppressants (IMMs) compared with VDZ monotherapy. Research suggests the use of concomitant aminosalicylates [5-ASAs] in UC may not bolster effectiveness. Finally, it is unclear if the safety profile differs between VDZ monotherapy and combo therapy. This study described clinical effectiveness and safety outcomes in patients with UC or CD treated with first-line biologic VDZ as monotherapy or combo therapy with IMMs or 5-ASAs (UC only). Methods This was a real-world, multi-country (Canada, Greece and the USA), retrospective chart review study of biologic-naïve UC and CD patients (≥18 years old) treated with VDZ (initiated Tx May 2014–March 2018). Data were collected from Tx initiation to the earliest of death and chart abstraction date. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan-Meier method with unadjusted comparisons conducted using the log-rank test. Clinical response and remission were assessed from standard disease measures reported in medical records. Analyses of unadjusted incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. For these analyses in monotherapy vs. VDZ+IMMs, UC and CD patients were combined due to restrictions of sample size and a number of events. Results This analysis included 318 patients treated with VDZ (monotherapy: UC = 53, CD = 108; VDZ+IMMs: UC = 22, CD = 24; VDZ+5-ASAs: UC = 111). There were no observed differences in age, sex or disease duration between patients on monotherapy vs. VDZ+IMMs or vs. VDZ+5-ASAs. Data trends in effectiveness outcomes were similar in monotherapy vs. VDZ+IMMs over 24 months (Figure 1). Tx persistence (monotherapy: 71.6%; VDZ+5-ASAs: 82.7%; p = 0.40), clinical remission (monotherapy: 54.3%; VDZ+5-ASAs: 87.7%; p = 0.37) and clinical response (monotherapy: 81.7%; VDZ+5-ASAs: 92.2%; p = 0.54) were also similar between monotherapy and VDZ+5-ASAs over 24 months. Safety outcomes were similar between groups (Figure 2). Conclusion Though sample sizes were small, the unadjusted trends in the results of this long-term real-world study suggest that biologic-naïve UC or CD patients treated with VDZ alone may have similar clinical effectiveness outcomes to patients receiving VDZ+IMMs. Trends in data also suggest that in patients with UC, VDZ+5-ASAs may not be more effective than VDZ alone.

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The Reasons for Discontinuation of Infliximab Treatment in Patients with Crohn's Disease: A Review of Practice at NHS Teaching Hospital

ISRN Gastroenterology ◽

10.5402/2011/672017 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Lukasz Z. Krupa ◽

Hugh J. Kennedy ◽

Crawford P. Jamieson ◽

Nicola Fisher ◽

Andrew R. Hart

Keyword(s):

Crohn’S Disease ◽

Side Effects ◽

Crohn's Disease ◽

Clinical Response ◽

Maintenance Treatment ◽

University Hospital ◽

Infliximab Treatment ◽

Refractory Disease ◽

Term Maintenance

Introduction. There is little information on the reasons for discontinuing infliximab treatment in patients with Crohn's disease. The aim of this study was to document these reasons to determine if any were preventable which would allow patients to continue the therapy. Aims & Methods. A review of the medical notes was conducted at the Norfolk and Norwich University Hospital on patients with Crohn's disease treated with infliximab between 2002–2008 to determine the reasons for stopping it. Results. A total of 65 patients were identified who had treatment with infliximab, of whom 23 (35.3%) had their therapy stopped. The reasons for discontinuation of infliximab in the 23 patients were: 47.8% side effects, 17.4% refractory disease, 13.0% achieved remission and did not receive long-term maintenance treatment, 4.34% pregnancy, 4.34% death, and unknown 13.0%. Conclusions. The main reasons for the discontinuation of infliximab were side effects rather than a lack of clinical response.

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Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn’s Disease Who Failed Biologic Therapies: A National Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz080 ◽

2019 ◽

Vol 13 (11) ◽

pp. 1401-1409 ◽

Cited By ~ 23

Author(s):

Claire Liefferinckx ◽

Bram Verstockt ◽

Ann Gils ◽

Maja Noman ◽

Catherine Van Kemseke ◽

...

Keyword(s):

Cohort Study ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Events ◽

Clinical Response ◽

Real World ◽

Clinical Remission ◽

De Novo ◽

Real World Data

Abstract Background Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn’s disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics. Methods This is an observational, national, retrospective multicentre study. Patients received intravenous UST ~6 mg/kg at baseline, with 90 mg subcutaneously thereafter every 8 weeks. Response and remission rates were assessed at Weeks 8, 16, and 52. Results Data from 152 patients were analysed. All patients were exposed to at least one anti-TNFα agent, with 69.7% were exposed to even two anti-TNFα and vedolizumab. After 1 year, 42.1% and 25.7% of patients had experienced clinical response and clinical remission, respectively, and 38.8% and 24.3% had achieved steroid-free clinical response and remission, respectively; 38.8% of patients discontinued therapy during the 12 months of follow-up. Colonic location was predictive of clinical response at 1 year, and low body mass index [BMI] at baseline was a negative predictor of clinical remission. Resolution of arthralgia was associated with clinical response over time. De novo arthralgia was reported by 17.9% of patients at Week 8 and 13.5% of patients at Week 52. No impact of UST on arthralgia was observed in patients with concomitant ankylosing spondylitis [n = 17]. Others adverse events were reported in 7.2% of patients. Conclusions This real-world cohort study confirms the effectiveness of UST in CD patients previously exposed to several biologics. Ustekinumab was well tolerated with respect to adverse events. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

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P389 Efficacy and safety of ustekinumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: real clinical practice

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.513 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S400-S401

Author(s):

R M Saiz Chumillas ◽

L Alba Hernández ◽

I Chivato Martín-Falquina ◽

E Badia Aranda ◽

M L Arias García ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Clinical Remission ◽

Real Life ◽

Corticosteroid Treatment ◽

Faecal Calprotectin ◽

Biochemical Remission

Abstract Background The efficacy of ustekinumab in patients with Crohn’s disease (CD) refractory to anti-TNF is worse than in anti-TNF naïve patients. Methods Retrospective study of patients with CD refractory or intolerant to TNF initiating ustekinumab between January 2013 and March 2020, with a minimum follow-up of 12 months, and without corticosteroid treatment. Our aim was evaluated clinical response (reduction of CDAI >100), clinical remission (CDAI <150) and biochemical remission (CDAI <100 and CRP <1 mg/L and faecal calprotectin <100 µg/g) in short and long term. Results A total of 49 patients with a medium follow-up of 28 months (IQR:13-37) were included. Patients baseline characteristics are reflected in Table 1. In 20% patients the induction was made subcutaneous (90 mg/week for 4 weeks). At week 52, clinical response, clinical remission and biochemical remission was 93%, 82% and 54% respectively (Figure 1). In the long term (3 years), 62% had clinical response, 52% remained in clinical remission, and 48% showed biochemical remission. 1/3 of patients needed intensification every year. Ustekinumab treatment discontinuation was observed in 13 patients (27%) mainly due to lack of response (6[12%]: primary, 7[14%]: secondary). No serious adverse effects have been reported. Conclusion About 50% of the patients are in clinical and biochemical remission at week 152 in a real-life cohort of anti-TNF-exposed CD patients. With a harder remission definition including biochemical parameters, our results in real life are similar to pivotal studies at week 152. Nevertheless, at week 52 our remission rates were higher.

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