Re-induction With Intravenous Ustekinumab in Patients With Crohn’s Disease and a Loss of Response to This Therapy

2021 ◽  
Author(s):  
Fernando Bermejo ◽  
Laura Jiménez ◽  
Alicia Algaba ◽  
Milagros Vela ◽  
Guillermo Bastida ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Serious Adverse Events ◽  
Protein Levels ◽  
Reactive Protein ◽  
Loss Of Response ◽  
Administration Interval ◽  
Safe Strategy

Abstract Background A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn’s disease who have lost the response to the treatment. Methods This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. Results Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. Conclusion Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn’s disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.

scholarly journals Vedolizumab Efficacy, Safety, and Pharmacokinetics With Reduced Frequency of Dosing From Every 4 Weeks to Every 8 Weeks in Patients With Crohn’s Disease or Ulcerative Colitis

2020 ◽  
Vol 14 (8) ◽  
pp. 1066-1073 ◽  
Author(s):  
Séverine Vermeire ◽  
Milan Lukáš ◽  
Fernando Magro ◽  
Shashi Adsul ◽  
Dirk Lindner ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Remission ◽  
Serious Adverse Events ◽  
Protein Levels ◽  
Reactive Protein ◽  
Reduced Frequency ◽  
Extended Access

Abstract Background and Aims Vedolizumab was shown to be safe and effective for the treatment of Crohn’s disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK. Methods Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events. Results Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. Conclusions In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.

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 Long-term follow up after switching from original infliximab to an infliximab biosimilar: real-world data

2019 ◽  
Vol 12 ◽  
pp. 175628481985805 ◽  
Author(s):  
María Fernanda Guerra Veloz ◽  
María Belvis Jiménez ◽  
Teresa Valdes Delgado ◽  
Luisa Castro Laria ◽  
Belén Maldonado Pérez ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Reactive Protein ◽  
Loss Of Response ◽  
Mayo Score ◽  
Inflammatory Bowel

Background: Several studies have reported positive efficacy outcomes for patients with inflammatory bowel disease treated with CT-P13, an infliximab biosimilar. Data from follow-up periods longer than 1 year are still scarce. Here, we assessed the long-term efficacy data, loss of response and safety after switching from infliximab to CT-P13 in patients with inflammatory bowel disease. Methods: This was a prospective single-center observational study involving patients with moderate-to-severe Crohn’s disease and ulcerative colitis switched from infliximab to CT-P13 treatment and reviewed up to 24 months. Efficacy and loss of response were measured using the Harvey–Bradshaw (HB) index and partial Mayo score for patients with Crohn’s disease and ulcerative colitis respectively. C-reactive protein, infliximab drug levels, adverse events and antidrug antibodies were also monitored throughout the study. Results: A total of 64 patients with Crohn’s disease and 36 patients with ulcerative colitis were included. Most of them (72%) remained on CT-P13. Overall, 28% of patients discontinued the therapy due to loss of response, adverse events or long-lasting clinical remission. Remission at 18 and 24 months occurred in 69.9% and 68.5% of patients, respectively. Dose increase was performed in 22% of patients, with remission being reached in 60% of them. HB index, partial Mayo score, C-reactive protein and infliximab drug levels did not show significant changes. Serious adverse events were reported in 14% of patients. Overall, two patients developed low levels of antidrug antibodies. Conclusions: Most of the patients switching from original infliximab were maintained on CT-P13 at 2 years of follow up with a good profile of efficacy and safety.

scholarly journals Adalimumab Dose-Escalation Therapy Is Effective in Refractory Crohn’s Disease Patients with Loss of Response to Adalimumab, Especially in Cases without Previous Infliximab Treatment

2019 ◽  
Vol 13 (1) ◽  
pp. 37-49
Author(s):  
Taketo Suzuki ◽  
Tsutomu Mizoshita ◽  
Tomoya Sugiyama ◽  
Yoshikazu Hirata ◽  
Yoshihide Kimura ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dose Escalation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Infliximab Treatment ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Loss Of Response

Background/Aims: Adalimumab dose escalation is one of the most important options in refractory Crohn’s disease patients with loss of response to adalimumab. The goal of this study was to evaluate the effectiveness of adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab, since there are few reports of adalimumab dose escalation, especially in East Asia. Methods: The clinical response to adalimumab dose escalation in Crohn’s disease patients with loss of response to adalimumab was evaluated retrospectively, using the Crohn’s disease activity index score, serum C-reactive protein levels, and endoscopic analyses. Results: Of the 203 Crohn’s disease patients treated with anti-tumor necrosis factor, 14 refractory Crohn’s disease patients with loss of response to adalimumab received adalimumab dose-escalation therapy. The C-reactive protein level was significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in the whole group, although there were no significant reductions of Crohn’s disease activity index scores. Both Crohn’s disease activity index scores and C-reactive protein levels were significantly reduced from the start to weeks 12 and 52 of adalimumab dose escalation in patients without previous infliximab treatment, although C-reactive protein levels were positive in all cases with previous infliximab exposure at weeks 12 and 52. Endoscopic mucosal healing was achieved with adalimumab dose escalation in 2 cases without previous infliximab treatment. Conclusions: Adalimumab dose-escalation therapy is effective in refractory Crohn’s disease patients with loss of response to adalimumab, especially in cases without previous infliximab treatment.

scholarly journals Safety of meningococcal group B vaccination in hospitalised premature infants

2018 ◽  
Vol 104 (2) ◽  
pp. F171-F175 ◽  
Author(s):  
Alison Kent ◽  
Kazim Beebeejaun ◽  
Serena Braccio ◽  
Seilesh Kadambari ◽  
Paul Clarke ◽  
...  
Keyword(s):  
Adverse Events ◽  
Premature Infants ◽  
Antibiotic Use ◽  
Neurological Status ◽  
Serious Adverse Events ◽  
Historical Cohort ◽  
Protein Levels ◽  
Reactive Protein ◽  
Before And After ◽  
Group B

ObjectivesTo assess the risk of significant adverse events in premature infants receiving the novel 4-component group B meningococcal vaccine (4CMenB) with their routine immunisations at 2 months of age.Participants, design and settingIn December 2015, Public Health England requested neonatal units across England to voluntarily participate in a national audit; 19 units agreed to participate. Anonymised questionnaires were completed for infants receiving 4CMenB alongside their routine immunisations. For comparison, a historical cohort of premature infants receiving their primary immunisations without 4CMenB or paracetamol prophylaxis was used.Main outcome measuresParacetamol use; temperature, cardiovascular, respiratory and neurological status before and after vaccination; and management and investigations postvaccination, including serum C reactive protein levels, infection screens and antibiotic use.ResultsComplete questionnaires were returned for 133 premature infants (<35 weeks’ gestation) who received their first dose of 4CMenB at 8 weeks of age, including 108 who received prophylactic paracetamol according to national recommendations. Overall, 7% (8/108) of infants receiving 4CMenB with paracetamol had fever (>38°C) after vaccination compared with 20% (5/25) of those receiving 4CMenB without paracetamol (P=0.06) and none of those in the historical cohort. There were no significant differences between cohorts in the proportion of infants with apnoea, bradycardia, desaturation and receiving respiratory support after vaccination.Conclusions4CMenB does not increase the risk of serious adverse events in hospitalised premature infants. This audit supports the current national recommendations to offer 4CMenB with other routine vaccinations and prophylactic paracetamol to premature infants at their chronological age.

scholarly journals P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S318-S319
Author(s):  
C Lansdorp ◽  
K Gecse ◽  
C Buskens ◽  
M Löwenberg ◽  
J Stoker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Hyperbaric Oxygen ◽  
Activity Index ◽  
Perianal Disease ◽  
Faecal Calprotectin ◽  
Preliminary Results ◽  
Patient Reported

Abstract Background Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results. Methods 17 patients with pCD refractory to conventional-therapy &gt; 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO. Results 17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p &lt; 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment. Conclusion Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.

scholarly journals P613 Use of adalimumab biosimilar ABP 501 in Crohn’s disease: A real-life experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S510-S511
Author(s):  
D G Ribaldone ◽  
M Vernero ◽  
R Pellicano ◽  
M Morino ◽  
G M Saracco ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Clinical Remission ◽  
Retention Rate ◽  
Real Life ◽  
University Hospital ◽  
Clinical Response Rate ◽  
Abp 501

Abstract Background The use of biologics in Crohn’s disease (CD) entails an increasing cost on national health systems. The use of biosimilars of adalimumab in CD is based on the concept of extrapolation of the results obtained in rheumatoid arthritis and in psoriasis, while no study about the efficacy and safety on CD of the biosimilars approved in Europe have been published. The aim of our study was to analyse, for the first time in literature, the effectiveness and safety of ABP 501 in CD patients naïve to adalimumab and its retention rate in CD patients who switched from adalimumab originator. Methods We performed an observational study on patients prospectively followed at the gastroenterology clinic of the Turin University Hospital. Inclusion criteria are (a) CD diagnosed according to ECCO criteria; (b) age ≥16 years; (c) initiation of therapy with ABP 501. Exclusion criterian is follow-up duration of less than 3 months for adalimumab-naïve patients, less than 6 months for patients who switched to ABP 501. Primary outcomes were (a) for patients treated with ABP 501 as first adalimumab: clinical response rate at 12 weeks and (b) for patients who switched to ABP 501: drug retention at 24 weeks. Secondary outcomes were (a) clinical remission rate at week 12 (for patients treated with ABP 501 as first adalimumab); (b) HBI and CRP reduction at week 12 (for patients treated with ABP 501 as first adalimumab), no significant change in HBI and CRP values at week 24 (for patients who switched to ABP 501); (c) analysis of predictors; and (d) adverse events incidence. Results Eighty-seven patients were included, of which 25 were naïve to adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, the clinical response at 3 months was 60% (15/25), clinical remission at 3 months was 56% (14/25). At 6 months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increment of clinical activity (Harvey–Bradshaw Index from 3.4, 95% CI = 2.4 – 4.4, to 3.8, 95% CI = 2.7 – 4.9, p = 0.23), and inflammatory biomarker (CRP from 4.2 mg/l, 95% CI = 2.5 mg/l – 5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2 mg/l – 5 mg/l, p = 0.32). No unexpected adverse events occurred during the study period. Conclusion Our results support ABP 501 as an efficacious and well-tolerated drug, at least in the short-term, and its interchangeability with its originator in the treatment of CD.

scholarly journals Tests that now deserve to be more widely adopted in IBD clinical practice

2020 ◽  
Vol 13 ◽  
pp. 175628482094408
Author(s):  
Nunzia Labarile ◽  
Subrata Ghosh ◽  
Siew C Ng ◽  
Julian Walters ◽  
Marietta Iacucci
Keyword(s):  
Crohn’S Disease ◽  
Clinical Practice ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Drug Efficacy ◽  
Individual Variability ◽  
Medical Decision ◽  
Aminosalicylic Acid ◽  
Biological Drugs ◽  
Serious Adverse Events

Inflammatory bowel diseases are chronic relapsing immune-mediated diseases of the intestinal tract with multifaceted manifestations and treatment related morbidity. Faecal and blood tests, radiological, endoscopic and histologic investigations are now widely used for managing both ulcerative colitis and Crohn’s disease. Over the years, a number of new investigations have been proposed but not widely adopted yet. Patients with Crohn’s disease may have multiple causes of diarrhoea, not always attributable to disease exacerbation, but sometimes linked to bile acid malabsorption; we have a reliable serum test, C4, that allows us to recognize and treat this cause of diarrhoea efficaciously and not empirically, but it is not available or used widely. There is genetic inter-individual variability in drug responses, in terms of both efficacy and toxicity, leading to high rates of therapeutic failure. Patients treated with thiopurine or, more rarely, 5-aminosalicylic acid may suffer from unpredictable and serious adverse events, some of these with pathogenesis related to genetic variants: myelosuppression, acute pancreatitis and nephrotoxicity. The identification of pre-treatment genetic tests can optimize therapeutic choice and avoid adverse events. With regard to biological drugs, patients can experience primary non-response or loss of response due to induction of immune responses to the drugs affecting drug efficacy and determining hypersensitivity reactions. We have specifically reviewed a number of investigations, whose use is currently limited, and highlighted four tests that deserve to be more widely incorporated in clinical practice as these could improve medical decision-making and patient outcomes.

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