scholarly journals Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease

2021 ◽  
Vol 8 (1) ◽  
pp. e000788
Author(s):  
Shaina Sekhri ◽  
Bharat Rao ◽  
Akanksha Mohananey ◽  
Poonam Beniwal-Patel ◽  
Alexandra Bruss ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Drug ◽  
Extraintestinal Manifestation ◽  
Cross Sectional ◽  
Patient Reported ◽  
Serum Trough ◽  
Inflammatory Bowel ◽  
Trough Levels ◽  
Serum Trough Levels

BackgroundInfliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.ObjectiveWe aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.DesignIn this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.ResultsOut of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).ConclusionsThis study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn’s disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.

scholarly journals P219 Disease-specific avoidance is a predictor for fatigue in inflammatory bowel disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S250-S252
Author(s):  
L Fierens ◽  
I Van de Pavert ◽  
M Walentynowicz ◽  
S Coenen ◽  
P Geens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Stool Frequency ◽  
Avoidance Behaviour ◽  
Tertiary Referral Centre ◽  
Cross Sectional ◽  
Patient Reported ◽  
Inflammatory Bowel ◽  
Disease Specific

Abstract Background A substantial group of patients with inflammatory bowel disease (IBD) experience fatigue, even while in clinical remission. At present, disease-specific behaviours that maintain or worsen symptom burden including fatigue have not been explored. We developed a questionnaire evaluating IBD-specific avoidance behaviour and investigated how this relates to self-reported fatigue. Methods This study was a close collaboration between the psychology and gastroenterology department of our tertiary referral centre. A 72-item IBD-specific avoidance behaviour questionnaire (IBD-B) was generated based on literature review and input from clinicians and a patient focus group (n = 10). Between July 2018 and March 2019, 500 consecutive IBD patients were included at our infusion unit (wave 1) (participation rate 79%, 48% male, 66% Crohn’s disease (CD), median age 40). Patients completed the 72-item IBD-B, a demographic questionnaire, patient-reported outcome assessing disease activity (PRO2) and a Visual Analogue Scale (VAS) for fatigue. Test–retest reliability was assessed in 89 patients (54% male, 70% CD, median age of 40) who completed the IBD-B, PRO2 and VAS fatigue scale a second time after 4–12 weeks (wave 2). Clinical remission was defined as an abdominal pain score ≤1 and a liquid to very soft stool frequency ≤1.5 in CD patients and as no rectal bleeding and a stool frequency ≤1 in patients with ulcerative colitis (UC). A principal component analysis (PCA) was then used to reduce the number of items and investigate the underlying factor structure of the IBD-B. The predictive value of IBD-specific behaviours for fatigue was finally investigated both cross-sectionally and prospectively. Results At wave 1, 46% and 69% of CD and UC patients, respectively, were in clinical remission. PCA suggested a reduction of the 72-item to a final 25-item IBD-B and a seven-factor solution for use in clinical practice (loading factors >0.5, Table 1). The final 25-item IBD-B showed good psychometric properties. The median (IQR) total IBD-B and fatigue scores were, respectively, 29 (40-20) and 52 (77-25) for patients in clinical remission compared with 38 (48-28) and 74 (87-50) for patients not in clinical remission (both p < 0.01). Both cross-sectional and prospective significant correlations between IBD-B factors and fatigue were demonstrated (Table 2). Conclusion The IBD-B is a valuable tool to accurately measure IBD-specific avoidance behaviour in IBD patients. IBD patients without clinical remission report higher IBD-B values and show a higher correlation between avoidance behaviour and fatigue. Further research should now focus on identifying predictors for fatigue in IBD patients in clinical remission.

The cost of treating inflammatory bowel disease: step-up vs step-down, therapeutic drug monitoring and personalised medicine

2021 ◽  
Vol 19 (4) ◽  
pp. 18-24
Author(s):  
Pearl Avery
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Personalised Medicine ◽  
Therapeutic Drug ◽  
Patient Reported ◽  
Inflammatory Bowel ◽  
Step Down

Inflammatory bowel disease (IBD) is a group of lifelong immune-mediated diseases, including Crohn's disease and ulcerative colitis. IBD is traditionally treated with drugs, including 5-aminosalicylates, steroids and immunosuppressants. However, the treatment landscape is changing, owing to a number of factors of significance to the IBD clinical nurse specialist. The recent introduction of novel biologic and biosimilar medications has affected the efficacy and cost of treatment. The established step-up treatment paradigm, where patients are started on simpler, cheaper therapies, is shifting toward a step-down approach, where biologics are the first-line treatment. Meanwhile, nurse-led pro-active therapeutic drug monitoring, including patient-reported outcome measures (PROMs), is helping ensure the efficacy and safety of treatment and allows for adjustments. In the near future, personalised medicine may offer genetic testing to predict a patient's reaction to different drugs and identify the most appropriate therapies. At the author's hospital, some of these factors may have contributed to a 50% reduction in emergency surgical rates for ulcerative colitis. This clinical review examines these issues in light of real-world experience from the author's hospital.

scholarly journals Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

2020 ◽  
pp. 1-10
Author(s):  
Ilana Reinhold ◽  
Sena Blümel ◽  
Jens Schreiner ◽  
Onur Boyman ◽  
Jan Bögeholz ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Disease ◽  
Therapeutic Drug ◽  
Real World Data ◽  
Significant Treatment ◽  
Infusion Reactions ◽  
Inflammatory Bowel ◽  
Trough Levels

<b><i>Background and Aims:</i></b> The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care. <b><i>Methods:</i></b> We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included. <b><i>Results:</i></b> The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (<i>p</i> = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (<i>p</i> = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9–38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients. <b><i>Conclusions:</i></b> TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

P329 Comparative Assessment of Adalimumab Trough Levels between Point-of-Care Testing and current Standard of Care (enzyme linked immunosorbent assay) in patients with Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S353-S353
Author(s):  
I Marsilio ◽  
D Maniero ◽  
G Lorenzon ◽  
A Rigo ◽  
R Cardin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Whole Blood ◽  
Point Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Point Of Care Testing ◽  
Deming Regression ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Adalimumab (ADL) is a therapeutic monoclonal antibody that targets the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and has been shown to effectively induce and maintain disease remission in patients with Inflammatory Bowel Disease (IBD). However, some patients fail to respond to this treatment, experiencing primary failure (no response to induction therapy), while others initially respond but lose efficacy over time (secondary failure). Therapeutic Drug Monitoring (TDM), in clinical practice, may lead to maintain therapeutic drug concentration thereby optimizing individual dosage regimen and improving treatment response. Recently, a point of care testing (POCT) has been developed to rapidly measure trough levels in patients taking ADL. Comparative data with current gold standard are lacking. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) ADL assay which analyze capillary whole blood and the comparative enzyme linked immunosorbent assays (ELISA) from serum samples. Methods From December 2020 to February 2021, consecutive patients (aged ≥ 18 years) taking ADA (Humira, Amgevita, Imraldi) were recruited at Gastroenterology Unit, Padua University Hospital, during outpatient visits. In each patient, ADL levels from capillary whole blood collected by finger stick were performed using the ProciseDx ADL assay with reportable range between 1.3 µg/mL - 51.5 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range ≤ 0.024 – 12 µg/mL). A Deming regression test was used to identify the correlation between the two methods. Results Sixty patients were enrolled (67% males with mean age of 3±14), with 80% of them having CD, 17% UC and 3% an undetermined-Inflammatory Bowel Disease (IBD-U). The assessment with ProciseDx POCT was feasible and required a turnaround time of 3±0.2 minutes while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. Thirty patients (63% males with mean age of 41±14) had therapeutic levels as assessed by ProciseDx ADL assay lower than 1.3 or greater than 12 µg/mL, in accordance with ELISA assessment. Among the remaining 30 patients (70% males with mean age of 43±15), the correlation between the two tests was high (r of 0.858 (95% CI 0.720 – 0.930)). Conclusion The ProciseDx POCT has similar accuracy but was more rapid and easy to be performed in providing the results of TDM in outpatients taking ADL. This could lead to a more rapid and effective optimization of the biological drug, thus avoiding treatment failure.

scholarly journals Ocular Affection as an Extraintestinal Manifestation in Cases of Inflammatory Bowel Disease at the Kafrelsheikh Governorate

2021 ◽  
Vol 41 (01) ◽  
pp. 008-013
Author(s):  
Mohammed Hussien Ahmed ◽  
Mohammed Elashery ◽  
Hebatallah Abdel Maksoud ◽  
Aya Mohammed Mahros
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
University Hospital ◽  
Ocular Involvement ◽  
Extraintestinal Manifestations ◽  
Extraintestinal Manifestation ◽  
Cross Sectional ◽  
Ocular Manifestations ◽  
Significant Difference ◽  
Inflammatory Bowel

Abstract Introduction The manifestations of inflammatory bowel disease (IBD) are not restricted to the gastrointestinal tract. Musculoskeletal conditions are considered the most common extraintestinal manifestations, followed by mucocutaneous and ocular diseases. Many general practitioners are unaware of the variety and severity of the ocular affection in IBD patients. Objective To assess the prevalence of extraintestinal manifestations in IBD patients at Kafrelsheikh governorate, and to evaluate the different ocular manifestations and their relationship to the severity of the disease. Methods A cross-sectional study evaluating 120 patients treated at the Kafrelsheikh University Hospital. The diagnosis of IBD was made between December 2018 and December 2019 through clinical, endoscopic and histopathological examinations. All patients were assessed for any extraintestinal manifestation or evidence of ocular affection through slit-lamp examinations, tonometry, visual acuity, and indirect ophthalmoscopy. Results The mean age of the sample was 35.5 ±  13.3 years. In total, 52 (43.3%) patients were male and 68 (56.7%) were female. Ocular manifestations represent ∼ 22.5% of extraintestinal manifestations. The most common ocular findings were conjunctivitis (25.8%) and anterior uveitis (10.8%), followed by scleritis (9.2%) and cataract (8.3%). Other extraintestinal manifestations were observed in 41 (34.1%) 29 (29.9%) of ulcerative colitis cases, and 12 (52%) of Crohn disease cases. There was no statistically significant difference in the presence of ocular involvement in relation to the two types of IBD included in the Montreal classification. Conclusion Ocular manifestations in cases of IBD are common and usually nonspecific in presentation. The severity of the IBD does not reflect the severity of the ocular affection.

scholarly journals Infliximab in young paediatric IBD patients: it is all about the dosing

2020 ◽  
Vol 179 (12) ◽  
pp. 1935-1944 ◽  
Author(s):  
Maria M. E. Jongsma ◽  
◽  
Dwight A. Winter ◽  
Hien Q. Huynh ◽  
Lorenzo Norsa ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Regimen ◽  
Bowel Disease ◽  
Maintenance Treatment ◽  
Young Patients ◽  
Intensive Treatment ◽  
Therapeutic Drug ◽  
Infliximab Treatment ◽  
Inflammatory Bowel ◽  
Trough Levels

AbstractInfliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years. What is Known? •Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year. What is New? •The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).

scholarly journals TNF Blocking Therapies and Immunomonitoring in Patients with Inflammatory Bowel Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Romain Altwegg ◽  
Thierry Vincent
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mucosal Healing ◽  
Primary Resistance ◽  
Current State ◽  
Serum Trough ◽  
Inflammatory Bowel ◽  
Trough Levels ◽  
Necrosis Factor

Since their appearance in the armamentarium for inflammatory bowel disease (IBD) more than a decade ago, antitumor necrosis factor (TNF) inhibitors have demonstrated beneficial activity in induction and maintenance of clinical remission, mucosal healing, improvement in quality of life, and reduction in surgeries and hospitalizations. However, more than one-third of patients present primary resistance, and another one-third become resistant over time. One of the main factors associated with loss of response is the immunogenicity of anti-TNF biologics leading to the production of antidrug antibodies (ADAbs) accelerating their clearance. In this review we present the current state of the literature on the place of TNF and its blockage in the treatment of patients with IBD and discuss the usefulness of serum trough levels and ADAb monitoring in the optimization of anti-TNF therapies.

scholarly journals P642 Serum adalimumab levels measured between days 9 and 13 from drug injection can be interpreted clinically in a similar way to trough levels in patients with inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S532-S532
Author(s):  
J Guardiola Capón ◽  
K Serra ◽  
L Rodríguez-Alonso ◽  
E Santacana ◽  
N Padullés ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Trough Level ◽  
Therapeutic Drug ◽  
Drug Injection ◽  
Time Points ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background AntiTNF therapeutic drug monitoring is currently performed at trough, immediately before drug administration. However, in clinical practice when subcutaneous medications are used, blood extractions often do not coincide with that moment. The aim of this study was to know if adalimumab levels measured between injections are sufficiently similar to trough levels to be used in clinical practice in a similar way. Methods 295 adalimumab level determinations performed at different time points of 99 injection cycles in 55 patients with inflammatory bowel disease (IBD) were included in the study. 51 patients received 40mg every 2 weeks and 4 patients received 80mg every 2 weeks. Results Median adalimumab levels (IQR) at trough, between days 1–4, 5–8 and 9–13 were 10.6 (6–12), 12.3 (7–18), 13 (7–19) and 10.8 (8–12), respectively. The median differences between trough level and days 1–4, 5–8 and 9–13 were 1.7 (IC 95% 1–2.3) (p &lt; 0.001), 2.3 (IC 95% 1.5–3.1) (p &lt; 0.001), 0.6 (IC 95% –0.2–1.3) (p = 0.13), respectively. Conclusion Adalimumab levels between days 9 and 13 from drug injection are very similar to trough level and could be interpreted clinically at the same way. Adalimumab levels between days 1 and 8 are significantly higher, although, differences are small.

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 &lt; 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 &lt; 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

Sign in / Sign up

Export Citation Format

Share Document