scholarly journals A229 USTEKINUMAB FOR THE TREATMENT OF REFRACTORY PEDIATRIC CROHN’S DISEASE: A SINGLE CENTRE EXPERIENCE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 104-106
Author(s):  
A Cohen ◽  
A Sant’Anna ◽  
N Ahmed
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
The Other ◽  
Secondary Loss ◽  
Loss Of Response

Abstract Background Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population. Aims We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission. Methods We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score. Results Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders. Conclusions These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy. Funding Agencies None

scholarly journals Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

2020 ◽  
Author(s):  
Mathurin Fumery ◽  
Laurent Peyrin-Biroulet ◽  
Stephane Nancey ◽  
Romain Altwegg ◽  
Cyrielle Gilletta ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Multicentre Study ◽  
Clinical Remission ◽  
Intestinal Resection ◽  
Serious Adverse Events ◽  
Faecal Calprotectin ◽  
Loss Of Response

Abstract Background The approved maintenance regimens for ustekinumab in Crohn’s disease [CD] are 90 mg every 8 or 12 weeks. Some patients will respond partially to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections. Methods All patients with active CD, as defined by Harvey–Bradshaw score ≥ 4 and one objective sign of inflammation [C-reactive protein > 5 mg/L and/or faecal calprotectin > 250 µg/g and/or radiological and/or endoscopic evidence of disease activity] who required ustekinumab dose escalation to 90 mg every 4 weeks for loss of response or incomplete response to ustekinumab 90 mg every 8 weeks were included in this retrospective multicentre cohort study. Results One hundred patients, with a median age of 35 years [interquartile range, 28–49] and median disease duration of 12 [7–20] years were included. Dose intensification was performed after a median of 5.0 [2.8–9.0] months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 [1.3–3.0] months. After a median follow-up of 8.2 [5.6–12.4] months, 61% of patients were still treated with ustekinumab, and 26% were in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission [no ulcers]. At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicentre study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

scholarly journals P498 Loss of response of anti-TNF in Crohn’s disease patients single-centre experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S434-S434
Author(s):  
A Atanassova ◽  
A C Georgieva ◽  
M Mirchev
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Biological Treatment ◽  
Phenotypic Expression ◽  
Faecal Calprotectin ◽  
Loss Of Response

Abstract Background Despite the timely commencement of the biological treatment, only about 30% will respond to it, and about 1/3 will lose the initial anti-TNF (tumour necrosis factor) response. Methods We retrospectively studied the data of 69 Crohn’s disease (CD) patients who started biological treatment with anti-TNF-ADA/ IFX. We excluded patients who are primary nonresponders to IFX/ADA. In patients with induction of clinical response, we investigated and analysed the frequency of subsequent loss of response (LOR) to IFX/ADA. We analysed the possible risk factors that have led to LOR. Results Of the 69 patients undergoing biological treatment, 71.01% achieved a clinical response during the course of the follow-up. There is a correlation between the presence of a clinical response and the CD course- x2 = 10.78, p = 0.013, ρ = 0.241, (p = 0.046). Inflammatory phenotype (В1) manifestation among our patients is a factor for achieving a clinical response OR = 3.68 (1.116–11.73), p = 0.021, whereas the presence of a penetrating form is a risk factor for the lack of response OR = 6.13 (1.29–29.01), p = 0.019. The presence of intestinal complications is a risk factor for the lack of response- OR = 3.2 (1.61–6.37), p = 0.001. During the course of the follow-up in 30.61% of cases, we observed LOR (men/women - 86.66%/13.33%, p < 0.05 (p = 0.02), in 60.00 % this was between 1–2 years, on average 20.62 ± 13.07 months from the start of the biological treatment. A total of 46.66% of patients required treatment with another anti-TNF drug due to secondary loss of response. A total of 50% of patients needed a reduction of the dose interval. Over 50.00% of those with LOR have an extensive disease (L3). A total of 40% have В1 and 33% have stricturing (В2) and penetrating (В3) phenotypic expression. In 26.66%, we observed progression of the disease range, and in 46.66% of patients - intestinal complications, none of whom had subsequent surgery. In 21.42% of LOR patients there is a combination of intestinal complications and progression according to disease localisation. 93.33% of CD patients with LOR have a persistence of extraintestinal manifestations (EIMs); those with two or three EIMs predominate. We discovered that gender was a risk factor for loss of response, OR = 8.36 (1.16–60.26), p = 0.005, as is the combination of В2 and В3 form of the disease OR = 14.72 (2.47–87.79), p = 0.003. Patients who lost response during the course of treatment had higher mean faecal calprotectin, CDAI and CRP prior to the initiation of the anti-TNF therapy. Conclusion The high activity of the disease measured with CDAI, faecal calprotectin and CRP, male gender, the combination of penetrating and stricturing form during the course of the disease are all risk factors for the loss of response.

scholarly journals P706 Adalimumab drug levels at secondary loss of response in Crohn’s disease; are we aiming high enough? A retrospective, international multi-centre study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S571-S572
Author(s):  
A Swaine ◽  
R Reynolds ◽  
X Roblin ◽  
D Gibson ◽  
C Martin ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Roc Analysis ◽  
Therapeutic Drug ◽  
Dose Intensification ◽  
Multi Centre Study ◽  
Drug Levels ◽  
Secondary Loss ◽  
Loss Of Response

Abstract Background Evidence supporting therapeutic drug monitoring with adalimumab (ADA) in Crohn’s disease (CD) is not as strong as for infliximab. Data examining whether changes in ADA drug exposure after dose intensification are associated with outcomes are lacking. We aimed to explore associations between ADA drug level exposure at loss of response and then at 6 and 12 months and compare these to short term clinical outcomes. Methods Retrospective study of adult CD patients who underwent ADA intensification to weekly dosing for secondary loss of response at three tertiary centres between 2013 and 2018. We compared trough ADA drug levels using a drug sensitive ELISA at loss of response and at 6 and 12 months after intensification with paired rates of clinical remission (Harvey Bradshaw Index <5 or Crohn’s Disease Activity Index <150), biochemical remission (C-reactive protein <5 mg/L), objective remission (CRP < 5 mg/L, faecal calprotectin < 150 µg/g or absence of inflammation at endoscopy or imaging) and ADA failure (based on Physicians Global Assessment. We performed comparisons between continuous and categorical data using Fischer’s exact or Mann–Whitney test. A receiver operated curve (ROC) analysis was used to identify target ADA levels associated with outcomes of interest. Results In total, 133 CD patients were included; median disease duration 8 years (IQR 4–17), 51% were biologic-exposed and 49% received concomitant immunomodulation. Rates of clinical remission, objective remission and ADA failure were 73.0%, 37.4% and 25.0% at 6 months and 65.8%, 34.0% and 42.8% at 12 months, respectively. Drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders; however increases in drug levels at 6 and 12 months were associated with improved outcomes at these time points (Figure 1). ROC analysis demonstrated that ADA drug levels 6 months after intensification > 8.9, 9.6 and 8.9 µg/ml were associated with clinical remission, objective remission and ADA non-failure respectively. Similar results were demonstrated with ADA drug levels at 12 months after dose intensification (Figure 1). Conclusion ADA drug levels at loss of response are not associated with subsequent 6 or 12 month outcomes. However, measurement of subsequent ADA drug levels at 6 and 12 months post escalation demonstrates that higher levels (with a target threshold between 7.7–10.9μg/ml) were associated with favourable outcomes. This study suggests that performing TDM subsequent to dose escalation of ADA has a role in predicting outcomes. Further, prospective studies dosing to target ADA drug levels are therefore needed.

scholarly journals Combination Ciprofloxacin and Metronidazole for Active Crohn’s Disease

1998 ◽  
Vol 12 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Susan L Greenbloom ◽  
A Hillary Steinhart ◽  
Gordon R Greenberg
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Intestinal Bacteria ◽  
Colonic Disease ◽  
Efficacy And Safety ◽  
Index Reduction ◽  
Ileal Disease

Recent experimental evidence underscores the contribution of intestinal bacteria to the inflammatory process of Crohn's disease. This open study examined the efficacy and safety of combination ciprofloxacin and metronidazole for patients with active Crohn's disease of the ileum and/or colon. Seventy-two patients with active Crohn's disease of the ileum (n=27), ileocolon (n=22) or colon (n=23) were treated with ciprofloxacin 500 mg bid and metronidazole 250 mg tid for a mean of 10 weeks. Clinical remission was defined as a Harvey-Bradshaw index of three points or less; an index reduction of at least three points indicated a clinical response. Clinical remission was observed in 49 patients (68%), and 55 patients (76%) showed a clinical response. A clinical response was noted in 29 of 43 patients (67%) who were not taking concurrent prednisone treatment and in 26 of 29 patients (90%) receiving prednisone (mean dose of 15 mg/day). A clinical response also occurred in a greater proportion of patients with colonic disease, with or without ileal involvement (84%), compared with patients with ileal disease alone (64%), and in patients without resection (86%) compared with those with previous resection (61%). Five patients discontinued antibiotics because of adverse events. After a mean follow-up of nine months, clinical remission was maintained in 26 patients off treatment and in 12 patients who continued antibiotic therapy. Ciprofloxacin in combination with metronidazole is well tolerated and appears to play a beneficial role in achieving clinical remission for patients with active Crohn's disease, particularly when there is involvement of the colon.

scholarly journals P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S578-S578
Author(s):  
A Viola ◽  
G Fiocco ◽  
A Alibrandi ◽  
F S Macaluso ◽  
M Cappello ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Demographic Data ◽  
Real Life ◽  
Primary Study ◽  
Clinical Activity ◽  
Secondary Failure

Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP). Results One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p < 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1). Conclusion Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.

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

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.

scholarly journals P559 Efficacy of Ustekinumab in the treatment of patients with Crohn’s disease with failure to previous conventional or biologic therapy: an observational real-life study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S522-S523
Author(s):  
A Miranda ◽  
A Cuomo ◽  
S Camera ◽  
C Ciacci ◽  
F R De Filippo ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Real Life ◽  
Mucosal Healing ◽  
Endoscopic Evaluation ◽  
Life Study

Abstract Background Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn’s disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. Methods The study was performed on 92 subjects (47 males; 45 females; mean age: 42 (17–78) from six medical centers in Campania, Italy, with confirmed diagnosis of moderate to severe Crohn’s disease and no neoplasia. In all patients diagnosis of CD had been reached to years earlier. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy.The administration of UST was as follows: IV infusion at week 0 (3 vials of 130 mg each if body weight of 55–85 kg; 2 vials of130 mg each if body weight < 55 kg) and subsequent SC injections (90 mg) q8w thereafter. At enrollment, all subjects underwent colonoscopy and were divided into groups according to endoscopic evaluation: 5 (5.4%) patients had erosions; 24 (26.1%) inflammation; 63 (68.5%) ulcers. Based on the CDAI value, 52 (56.5%) patients had a CDAI of 180–220, 35 (38%) had a CDAI of 220–450, and 5 (5.4%) had a CDAI >450. All patients underwent endoscopic examination and bowel MRI or ultrasonography at baseline and at week 52 to evaluate mucosal and transmural healing. Clinical response was defined as a reduction of CDAI by at least 100 points; clinical remission when CDAI was lower than 150. Clinical response and remission were evaluated at baseline and on 5 different occasions throughout a 12 months follow-up. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Results Seventeen patients interrupted therapy while 75 patients continued follow-up until the fifth visit. Clinical response at week 52 was achieved in 38 (50,5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. Fifteen patients (20%) did not show any change during endoscopic evaluation at follow-up. All patients showing mucosal healing also showed transmural healing, as assessed by ultrasonography or MRI. No major TRAEs were observed during treatment. Conclusion In this multi-center, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

P084 DEEP REMISSION WITH DOUBLE BIOLOGIC THERAPY: A SUCCESSFUL CASE OF COMBINATION USTEKINUMAB AND VEDOLIZUMAB FOR SEVERE REFRACTORY CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S72-S72
Author(s):  
Ahmed Elmoursi ◽  
Courtney Perry ◽  
Terrence Barrett
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Case Reports ◽  
Sigmoid Resection ◽  
Safety And Efficacy ◽  
Ileal Stricture

Abstract Background Stricturing Crohn’s disease (CD) constitutes a severe phenotype often associated with a high degree of morbidity (3). Surgical resection is first-line therapy for symptomatic strictures, but most patients relapse without subsequent medical therapy (4–5). Biologics are the mainstay for inducing and maintaining remission, but some cases are refractory despite maximum dosage of therapy. Reports of dual biological therapy (DBT) in refractory, stricturing CD are sparse, and prior case reports document only clinical remission (1). To contribute further knowledge regarding the use of DBT in stricturing CD, we present the case of a refractory CD patient who achieved deep remission with ustekinumab and vedolizumab. Case Presentation A 35 year old non-smoking, Caucasian male was referred to our clinic in 2014 for refractory CD complicated by multiple strictures. Prior to establishing care with us, he received two jejunal resections and a sigmoid resection. Previously failed therapies included azathioprine with infliximab, adalimumab, and certolizumab. He continued to progress under our care despite combination methotrexate/certolizumab, as well as methotrexate/golimumab. He underwent proctocolectomy with end ileostomy in 2015 and initiated vedolizumab q8weeks post-operatively. He reoccurred in 2018, when he presented with an ulcerated ileal stricture. He was switched from vedolizumab to ustekinumab q8weeks and placed on prednisone, but continued to progress, developing significant hematochezia requiring hospitalization and blood transfusions. Ileoscopy performed during hospital admission confirmed severe, ulcerating disease in the ileum with stricture. Ustekinumab dosing was increased to q4weeks, azathioprine was initiated, and he underwent stricturoplasty. Follow-up ileoscopy three months later revealed two ulcers in the neo- TI (Figure 1). Vedolizumab q8weeks was initiated in addition to ustekinumab q4weeks and azathioprine 125mg. After four months on this regimen the patient felt better, but follow-up ileoscopy showed two persistent ulcers in the neo-TI. Vedolizumab dosing interval was increased to q4weeks. After four months, subsequent ileoscopy demonstrated normal neo-TI (Figure 2). Histologic evaluation of biopsies confirmed deep remission of crohn’s disease. No adverse side effects have occurred with maximum doses of both ustekinumab and vedolizumab combination therapy. Discussion This case supports both the safety and efficacy of ustekinumab and vedolizumab dual biologic therapy for treatment of severe, refractory Crohn’s disease. While there are reports of DBT inducing clinical remission, this case supports efficacy for vedolizumab and ustekinumab combination therapy to induce deep histologic remission. Large practical clinical trials are needed to better investigate the safety and efficacy of DBT with vedolizumab and ustekinumab, but our case suggests this combination may be a safe and efficacious therapy for refractory CD patients.

P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Clinical Disease ◽  
Endoscopic Remission ◽  
Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with >3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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