scholarly journals P481 Effectiveness and safety profile of biological therapy in inflammatory bowel disease: real life data from an active pharmacovigilance project

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S470-S471
Author(s):  
A Viola ◽  
M A Barbieri ◽  
V Pisana ◽  
P M Cutroneo ◽  
W Fries ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Safety Profile ◽  
Index Date ◽  
Descriptive Analysis ◽  
Real Life ◽  
Biologic Agent ◽  
Skin Reactions ◽  
Inflammatory Bowel

Abstract Background Biological therapies are now the mainstay for the treatment of Inflammatory bowel disease (IBD). Post-marketing activities become crucial for monitoring the long-term safety. Aim of this project was to evaluate the effectiveness and the safety profile of biologics for the treatment of IBD patients during a prospective pharmacovigilance study. Methods From January 2017 to December 2020, all patients with Crohn’s Disease (CD) and Ulcerative Colitis (UC) treated with at least one biologic agent at the start of the study or commenced a biologic during the study period were enrolled. Demographic, clinical, and disease-related data were collected. A descriptive analysis of patients’ characteristics at the index date was performed. Moreover, an analysis of all adverse events (AEs) and all primary/secondary failures expressed as number of AEs or failures/10 treatment years was carried out taking into account the total years of treatment for each biologic including all patients treated with a biologic at least once during the follow-up period. Results A total of 654 patients were enrolled, 58.4% with CD and 41.6% with UC. Mean age (±SD) was 44 ± 17 years and 59.0% were males. At the index date, the following treatments were used: 40.8% adalimumab (ADA), 33.3% infliximab (IFX), 21.3% vedolizumab (VED), 2.4% ustekinumab (UST), and 2.1% golimumab (GOL). Patients naïve for biologic therapy were 79.1%. The total years of treatment were 887 yrs for ADA, 663 yrs for IFX, 309 yrs for VED, 89 yrs for UST, and 51 yrs for GOL. Data for AEs and failures were the following: IFX – 1.1 AEs and 0.8 failures, ADA – 0.8 and 0.9, VED – 1.1 and 1.8, GOL – 1.2 and 3.4, and UST - 1.4 and 0.9, respectively (Tab.1). During follow-up, 196 AEs were reported. Infections mainly occurred in patients treated with GOL and ADA (8.7% and 7.6%, respectively), skin reactions in patients treated with ADA (7.6%), while infusion related reactions with IFX (12.6%). A higher frequency of malignancies was observed in patients on treatment with VED (3.4%). Conclusion There were no major differences for AEs between the different treatments, but a higher frequency of failures with GOL and VED, both rarely used as first line therapies. Nevertheless, the acquisition of data from clinical practice should be endorsed to better define the safety and efficacy profile of new biologic agents in IBD.

scholarly journals P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S355-S355
Author(s):  
M I Calvo Moya ◽  
I Omella Usieto ◽  
M I Vera Mendoza ◽  
V Matallana Royo ◽  
I Gonzalez Partida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Mucosal Healing ◽  
Surveillance Colonoscopy ◽  
Previously Treated ◽  
Inflammatory Bowel

Abstract Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was defined by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was defined by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline. Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

scholarly journals P533 Adalimumab 80mg every other week in inflammatory bowel disease: Treatment intensification outcomes in real life clinical practice

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S507-S509
Author(s):  
M I Calvo Moya ◽  
I Omella Usieto ◽  
I El Hajra Martinez ◽  
E Santos Perez ◽  
Y Gonzalez Lama ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Smoking Habit ◽  
Real Life ◽  
Fecal Calprotectin ◽  
Treatment Intensification ◽  
Loss Of Response ◽  
Inflammatory Bowel

Abstract Background Adalimumab (ADA) intensification is recommended for inadequate or loss of response in inflammatory bowel disease (IBD) patients. A new presentation of ADA 80mg administered every other week (eow) has been approved as an alternative to ADA 40mg every week (ew). Data regarding impact of ADA 80mg eow in clinical practice is still scarce. The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. Methods A retrospective cohort study in a tertiary hospital that included all IBD patients under intensified maintenance therapy with ADA 80mg eow was performed. Durability was calculated considering the time from the first dose to treatment withdrawn or to the end of follow-up. Biological remission (BR) was defined as CR together with fecal calprotectin (FC) <250µg/g and C-reactive protein (CRP) <5mg/dl. Economic impact of ADA 80mg eow was estimated considering current price of both ADA 40mg and ADA 80mg pens at our centre. Results Sixty-three patients (52 CD and 11 CU) were included; median age 47 (IQR 39–59), 54% male; median duration of the disease before ADA of 11 years (IQR 6–20); 30% were active smokers. Among CD patients, 56% had ileal disease, 17% colonic and 27% ileocolonic. The inflammatory behavior was the most frequent (52%) and 31% had perianal disease. In UC, 55% had extensive colitis. 44 patients (70%) were bio-naïve and 36 (57%) received immunosuppressants at baseline. At the time of escalation, 48 patients (76%) were symptomatic. After intensification, 52 (83%) patients (CD 42 and UC 10) achieved CR and 46 (73%) BR. The changes in the levels of FC, CRP and ADA were significant (p <0.001) (Graphs 1–3). 22 patients (35%) discontinued treatment after a median of 6.5 (IQR 5–10) months due to: 11 no clinical response (50%), 4 loss of response (18%), 3 adverse events (14%) (psoriasis) and 4 endoscopic progression (18%). 44 patients (70%) remained under treatment and in CR (median follow-up 17 months, IQR 13–24) (Graph 4) and with a median ADA levels of 10.46 mg/l (IQR 7.34–15.25). Use of ADA 80 eow regimen saved 223500€ in patients who maintained treatment. In the multivariate analysis, being in CR when intensifying reduced the risk of treatment discontinuation by 87% (HR 0.13, 95%CI 0.02–0.99; p<0.001), having reached BR by 99.5% (HR 0.05, 95%CI 0.02–0.14; p <0.001) and having ADA levels ≥5 mg/l after intensification by 68% (HR 0.32, 95%CI 0.13–0.75; p = 0.02). Smoking habit was associated with treatment withdrawn (HR 1.74, 95%CI 1.02–2.96; p=0.04). Conclusion ADA intensification to 80mg eow in IBD patients is safe, effective and may reduce costs in real life clinical practice. Early intensification, even in CR, may enhance ADA treatment durability.

scholarly journals Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies

2020 ◽  
Author(s):  
William J Sandborn ◽  
Brian G Feagan ◽  
Silvio Danese ◽  
Christopher D O’Brien ◽  
Elyssa Ott ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Safety Profile ◽  
Phase 2 ◽  
Phase 3 ◽  
Number Of Patients ◽  
Serious Infections ◽  
Inflammatory Bowel

Abstract Background Ustekinumab is currently approved globally in Crohn’s disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn’s disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses. Methods Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed. Results Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81–176.67] vs ustekinumab 118.32 [95% CI, 113.25–123.55]), serious AEs (27.50 [95% CI, 23.45–32.04] vs 21.23 [95% CI, 19.12–23.51]), infections (80.31 [95% CI, 73.28–87.84] vs 64.32 [95% CI, 60.60–68.21]), serious infections (5.53 [95% CI, 3.81–7.77] vs 5.02 [95% CI, 4.02–6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00–0.93] vs 0.40 [95% CI, 0.16–0.83]) were similar between placebo and ustekinumab. Conclusions The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications. ClinicalTrials.gov numbers NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.

scholarly journals P477 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of inflammatory bowel disease: the elderly cohort

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S419-S422
Author(s):  
D Pugliese ◽  
G Privitera ◽  
A Armuzzi
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Real Life ◽  
Treatment Persistence ◽  
Diagnosis Of Cancer ◽  
Inflammatory Bowel ◽  
New Diagnosis

Abstract Background Vedolizumab (VDZ) is the first biological therapy for Inflammatory Bowel Disease (IBD) tested, in pivotal trials, on patients up to 80 years old and has usually been presented as a safer choice in frail patients. However, real-world data on the effectiveness and safety of VDZ in elderly (≥ 65 years) are scarce. The aim of this study is to explore the effectiveness and safety of VDZ in a large real-life cohort of elderly IBD patients, with a 2 years follow-up. Methods The Long-term Italian Vedolizumab Effectiveness (LIVE) study included CD and UC patients started on VDZ from April 2016 to June 2017 at 40 centres of the Italian Group for the study of inflammatory bowel disease (IG-IBD). Patients were prospectively followed-up to June 2019. Co-primary endpoints were to evaluate cumulative VDZ treatment persistence and safety. Results Of 966 patients, 174 (18%; 81 CD, 93 UC) were ≥ 65 years old at enrolment. Mean disease duration at baseline was 10.9 years ± SD10 (CD 12.5 ± 11, UC 9.6 ± 9). VDZ was used as a first biologic therapy in 78 patients (44.8%). 25 patients (14.4%) had a history of previous cancer. The majority of CD patients had a stricturing behaviour (45, 55.6%) and had already undergone surgery (41, 49.4%). 48 UC patients (51.6%) had extensive colitis. Moderate-to-severe endoscopic activity was present in 80% of CD and in 92% of UC, according to SES-CD and endoscopic Mayo score, respectively. Cumulative VDZ treatment persistence at 12 and 24 months was 71.8% (71.6% CD and 72.0% UC) and 54% (54.2% CD and 53.8%% UC), respectively. 52.9% (40 CD; 52 UC), 4.0%, 3.5%% and 2.9% of patients were on concomitant steroids at baseline, 6, 12, and 24 months, respectively. Clinical remission at 12 and 24 months was achieved in 28.7% (31 CD and 29 UC) and in 31.6% (25 CD and 30 UC) of patients. Mean C-reactive protein was 15.6 mg/l ± SD 20 (CD 15.9 ± 21; UC 15.2 ± 19) at baseline and dropped to 8.4 mg/l ± 10 (CD 8.0 ± 8, UC 8.9 ± 11) at 12 months and to 5.9 mg/l ± 6 (CD 5.8 ± 5, UC 6 ± 7) at 24 months. Dose escalation was necessary for 20.3% and 24.7% of patients within the first 12 and 24 months. 44 adverse events were reported: 16 infections.,6 new diagnosis of cancer/dysplasia (2 colon, 1 kidney, 1 prostate, 1 lung, 1 melanoma), 4 arthritis, 3 skin rash, 2 drug-induced cholestasis,11 miscellaneous. 11 patients (6.3%) underwent VDZ withdrawal because of adverse events (6 new diagnosis of cancer/dysplasia; 4 infections; 1 cholestasis). One patient died for pneumonia complications. Conclusion In this preliminary analysis of the largest reported real-world cohorts of elderly IBD patients treated with VDZ, up to 55% of patients persisted on therapy after two years; an acceptable safety profile was observed throughout the entire follow-up period.

scholarly journals Safety profile of anti-tumor necrosis factor therapy in inflammatory bowel disease – a single center experience

2015 ◽  
Vol 84 (3) ◽  
pp. 146-151
Author(s):  
Piotr Eder ◽  
Liliana Łykowska-Szuber ◽  
Iwona Krela-Kaźmierczak ◽  
Kamila Stawczyk-Eder ◽  
Katarzyna Klimczak ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Tumor Necrosis Factor ◽  
Bowel Disease ◽  
Safety Profile ◽  
Tumor Necrosis ◽  
Real Life ◽  
Concomitant Treatment ◽  
Single Center Experience ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Introduction. The data on the safety profile of anti-tumor necrosis factor (anti-TNF) therapy in real-life patients cohorts with inflammatory bowel disease (IBD) still are lacking.Aim. The aim of the study was to assess the adverse events (AE) of anti-TNF therapy in a single Polish IBD center. Material and methods. Data on the safety of anti-TNF therapy among Crohn’s disease (CD) and ulcerative colitis (UC) patients treated in years 2009–2015 at the Department of Gastroenterology, Human Nutrition and Internal Diseases of Poznań University of Medical Sciences were analyzed.Results. There were 41 AE/188 therapies reported (21.8%) – 39/176 (22.1%) in CD and 2/12 (16.6%) in UC patients. The most common AE were infections – 10.1%, followed by dermatological complications – 2.6%, and infusion allergic reactions – 2.1%. The majority of AE (27/41 – 66%) were treated successfully or resolved without a treatment. The frequency of AE among patients treated with different molecules was similar – 17/85 (20%) in the adalimumab group, 20/91 (21.9%) in the originator infliximab group, and 4/18 (22.2%) in the biosimilar infliximab group. Concomitant treatment seemed not to influence the AE risk.Conclusions. Anti-TNF therapy, which is used among the most severely ill IBD patients, seems to be safe. However, further assessment is needed in real-life patients cohorts, especially to assess the long-term safety of anti-TNF treatment in IBD.

scholarly journals P408 Long-term impact of the decrease of infliximab trough levels on the disease course in Inflammatory Bowel Disease patients under maintenance treatment with infliximab

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S375-S376
Author(s):  
E Orfanoudaki ◽  
M Gazouli ◽  
K Foteinogiannopoulou ◽  
E Theodoraki ◽  
E Legaki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Biologic Agent ◽  
Therapeutic Drug ◽  
Asymptomatic Patients ◽  
Treatment Optimisation ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background The measurement of infliximab trough levels (IFX-TLs) has been suggested as an important biomarker for the optimisation of treatment in patients with inflammatory bowel disease (IBD). We have previously reported that IFX-TLs of patients under maintenance treatment with IFX show decreasing patterns associated with an increasing pattern of CRP levels1. We aimed to study the clinical impact of this observation by recording the treatment changes that became necessary during a three year follow-up. Methods Consecutive asymptomatic patients on maintenance treatment with IFX were included. Two different measurements of IFX-TLs were made (ELISA, Eagle BioSciences) with a ten-month interval using serum samples drained before IFX infusion. After the second measurement patients were followed up for three years and all treatment modifications including IFX intensification, change of biologic agent or IBD-related surgical intervention were assessed. Results Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 CD, 15 UC, 42 men, mean age 44.2 ± 15.2 years, 41 in combination therapy with immunomodulator, 6 in intensified dose], with 2 available measurements of IFX-TLs (A and B) were included in the study. Median levels of IF-TLs were 5.07 (IQR 1.60–12.73) μg/ml in measurement A and 4.68 (1.19–7.83) μg/ml in measurement B (p < 0.0001). Treatment was intensified in 8 patients after measurement A. Patients with stable IFX dose showed a significant reduction in median IFX-TLs from 5.65 to 3.8 μg/ml (p < 0.0001). Moreover, CRP levels were significantly increased in measurement B compared with measurement A [0.33 (03–4.4) mg/dl vs. 0.31 (0.3–3.8) mg/dl, p = 0.02]. During a 3 year follow-up, 22 (34%) patients needed treatment optimisation (6 IFX intensification, 7 change of agent, 6 surgery, 3 change of agent plus surgery). In three patients IFX was stopped for safety reasons. Fifty-eight hospitalisations in 19 patients were also recorded. The decrease of IFX-TLs between the two measurements was significantly more in patients with treatment optimisation compared with patients without treatment optimisation (p = 0.03). Conclusion IBD patients who are on maintenance treatment with infliximab showing decreasing patterns of IFX-TLs often need treatment optimisation during the follow-up due to clinical or endoscopic activity. These results probably suggest the importance of the proactive therapeutic drug monitoring and early treatment optimisation in these patients References

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