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British Journal of Clinical Pharmacology Oct 2021Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab...
AIMS
Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety.
METHODS
Retrospective case-control data of patients receiving infliximab induction treatment were analysed. A population pharmacokinetic model was developed to estimate individual pharmacokinetic parameters. A logistic regression model was used to investigate the effect of exposure on endoscopic remission. Repeated time-to-event models were developed to describe the hazard of safety events over time.
RESULTS
A total of 104 patients (46 elderly, ≥65 years) were included. A two-compartment population pharmacokinetic model with linear elimination adequately described the data. Infliximab clearance decreased with older age, higher serum albumin, lower fat-free mass, lower C-reactive protein and absence of immunogenicity. Yet, infliximab exposure was not significantly different between elderly and nonelderly. Regardless of age, an infliximab trough concentration at week (w)14 of 15.6 mg/L was associated with a 50% probability of attaining endoscopic remission between w6 and w22. Infliximab exposure during induction treatment was not a risk factor of (severe) adverse events. The hazard of severe adverse events and malignancy increased by 2% and 7%, respectively, with increasing year of age. Concomitant immunomodulator use increased the hazard of infection by 958%, regardless of age.
CONCLUSIONS
Elderly patients attained infliximab exposure and endoscopic remission similarly to nonelderly patients. Therefore, the same infliximab trough concentration target can be used in therapeutic drug monitoring. The hazards of severe adverse events and malignancy increased with age, but not with infliximab exposure.
Topics: Aged; Aging; Drug Monitoring; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Retrospective Studies; Treatment Outcome
PubMed: 33604964
DOI: 10.1111/bcp.14785 -
United European Gastroenterology Journal Feb 2021Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal...
BACKGROUND
Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics.
METHODS
The study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy (n = 119), the first trimester (n = 16), second trimester (n = 18), third trimester (n = 7), and postpregnancy (n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modeling.
RESULTS
Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 mg/ml/kg, interquartile range 10-21) compared to prepregnancy (7, 2-12; p = 0.003), the first trimester (9, 1-12; p = 0.04), or postpregnancy (6, interquartile range 3-11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7-36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution n = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and postpregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester.
CONCLUSION
Infliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.
Topics: Drug Monitoring; Female; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Proof of Concept Study; Retrospective Studies; Tumor Necrosis Factor-alpha
PubMed: 33079627
DOI: 10.1177/2050640620964619 -
BioDrugs : Clinical Immunotherapeutics,... May 2023We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars)...
OBJECTIVE
We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab.
METHODS
An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU.
RESULTS
Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA.
CONCLUSIONS
Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.
Topics: Humans; Infliximab; Biosimilar Pharmaceuticals; Interrupted Time Series Analysis; India
PubMed: 36952213
DOI: 10.1007/s40259-023-00589-3 -
Expert Review of Clinical Immunology Jan 2021There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA). (Comparative Study)
Comparative Study Meta-Analysis
Efficacy and safety of subcutaneous infliximab versus adalimumab, etanercept and intravenous infliximab in patients with rheumatoid arthritis: a systematic literature review and meta-analysis.
OBJECTIVES
There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).
METHODS
Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621).
RESULTS
The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept.
CONCLUSION
CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.
Topics: Adalimumab; Administration, Cutaneous; Administration, Intravenous; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Etanercept; Humans; Infliximab; Treatment Outcome
PubMed: 33305638
DOI: 10.1080/1744666X.2020.1858803 -
Current Oncology (Toronto, Ont.) Jun 2021Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing...
BACKGROUND AND AIMS
Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage. As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs).
METHODS
We retrospectively reviewed consecutive patients treated with infliximab for irAEs at Princess Margaret Cancer Centre. To assess hepatotoxicity, we compared the mean value of ALT, AST, and total bilirubin (BT) before and after infliximab treatment. We used logistic regression to assess factors associated with infliximab efficacy.
RESULTS
Between January 2010 and February 2019, 56 patients were identified. The median age of the patients was 63 (27-84) years. Colitis was the most frequent toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat ir-hepatitis in one patient. The median number of infliximab doses was 1 (1-3) and led to toxicity resolution in 43 (76%) patients. The mean ALT, AST, and BT levels before and after infliximab treatment were not statistically different. The patient treated for ir-hepatitis had a complete recovery, with no incremental liver toxicity.
CONCLUSIONS
In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity.
Topics: Aged; Aged, 80 and over; Chemical and Drug Induced Liver Injury; Humans; Infliximab; Middle Aged; Retrospective Studies; Steroids
PubMed: 34208089
DOI: 10.3390/curroncol28030201 -
The American Journal of Gastroenterology Sep 2023Immune checkpoint inhibitor-mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC...
INTRODUCTION
Immune checkpoint inhibitor-mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC refractory to steroids plus infliximab and/or vedolizumab.
RESULTS
Nineteen patients were treated with UST for IMC refractory to steroids plus infliximab (57.9%) and/or vedolizumab (94.7%). Most of them had grade ≥3 diarrhea (84.2%), and colitis with ulceration was present in 42.1%. Thirteen patients (68.4%) attained clinical remission with UST, and mean fecal calprotectin levels dropped significantly after treatment (629 ± 101.5 mcg/mg to 92.0 ± 21.7 mcg/mg, P = 0.0004).
DISCUSSION
UST is a promising therapy for the treatment of refractory IMC.
Topics: Humans; Infliximab; Colitis; Ustekinumab; Interleukin-12
PubMed: 37216614
DOI: 10.14309/ajg.0000000000002332 -
Dermatology (Basel, Switzerland) 2023Ten-year survival and retention rate data on biologics are extremely limited, and there is a need to evaluate these metrics based on real-world data as well as on the...
BACKGROUND
Ten-year survival and retention rate data on biologics are extremely limited, and there is a need to evaluate these metrics based on real-world data as well as on the results of clinical studies.
OBJECTIVE
The objective of this study was to assess the long-term survival rates of adalimumab and infliximab in real-life practice.
METHODS
This study is based on data from the Turkish Psoriasis Registry and the digital records of the Medical School of Bezmialem Vakif University. Baseline data including demographic characteristics, duration of treatment, use of combination treatments, modified regimens, and reasons for treatment termination were extracted.
RESULTS
In total, 404 patients (228 on adalimumab and 176 on infliximab) treated between July 1, 2005, and December 31, 2020, were identified. The retention rate was 7.4% for infliximab and 3.5% for adalimumab after 10 years (p = 0.85).
CONCLUSIONS
The efficacy of infliximab and adalimumab diminishes over time. There were no significant differences in the retention rate between the two drugs, but the survival time was longer for infliximab according to Kaplan-Meier analysis.
Topics: Humans; Adalimumab; Infliximab; Psoriasis; Etanercept; Treatment Outcome
PubMed: 36871548
DOI: 10.1159/000529964 -
Medicine Aug 2018Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients with moderate-to-severe and steroid-refractory UC.
METHODS
A literature search identified studies that investigated tacrolimus and IFX in moderate-to-severe steroid-refractory patients with UC. The primary outcome was short-term clinical response to treatment, including the remission and response rates. Secondary outcomes included the rates of colectomy at 3 months and adverse events rate.
RESULTS
A total of 6 studies comprising 438 cases were eligible for inclusion. The pooled analysis showed that the short-term clinical response rate, clinical remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%, respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%, respectively, for those receiving IFX. No significant difference was, however, seen for tacrolimus compared with IFX with regard to clinical remission rate (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67), clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P = .006).
CONCLUSIONS
Our meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for these patients.
Topics: Adult; Colitis, Ulcerative; Female; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Induction Chemotherapy; Infliximab; Male; Tacrolimus; Treatment Outcome
PubMed: 30095612
DOI: 10.1097/MD.0000000000011440 -
Alimentary Pharmacology & Therapeutics Jan 2019Biosimilar versions of widely prescribed drugs, including the tumour-necrosis factor antagonist infliximab, are becoming increasingly available. As biosimilars are not...
BACKGROUND
Biosimilar versions of widely prescribed drugs, including the tumour-necrosis factor antagonist infliximab, are becoming increasingly available. As biosimilars are not identical copies of reference products, evidence may be required to demonstrate that switching between a reference biologic and biosimilars is safe and efficacious. To establish interchangeability, US Food and Drug Administration guidance states that studies must demonstrate that biosimilars remain equivalent or non-inferior to a reference product after multiple switches between products.
AIMS
To investigate the evidence evaluating the safety and efficacy of switching between reference and biosimilar infliximab in patients with inflammatory disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
METHODS
Published studies presenting data on switching between reference and biosimilar infliximab were identified by searching the MEDLINE database. Congress abstracts were identified by searching the EMBASE database and manually searching abstracts from relevant congresses.
RESULTS
A total of 113 journal articles and 149 abstracts were found. Of these, 70 were considered relevant and included in this analysis. Most of the publications were uncontrolled, observational studies. Data from six randomised, controlled trials were identified. In general, the evidence revealed no clinically important efficacy or safety signals associated with switching.
CONCLUSIONS
While available data have not identified significant risks associated with a single switch between reference and biosimilar infliximab, the studies available currently report on only single switches and were mostly observational studies lacking control arms. Additional data are needed to explore potential switching risks in various populations and scenarios.
Topics: Biological Factors; Biosimilar Pharmaceuticals; Humans; Infliximab; Randomized Controlled Trials as Topic; Treatment Outcome; Tumor Necrosis Factor-alpha; United States; United States Food and Drug Administration
PubMed: 30411382
DOI: 10.1111/apt.14997 -
Digestive Diseases and Sciences May 2024Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.
BACKGROUND
Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC).
AIMS
This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC.
METHODS
Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis.
RESULTS
Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks.
CONCLUSIONS
Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.
Topics: Humans; Infliximab; Antibodies, Monoclonal, Humanized; Injections, Subcutaneous; Gastrointestinal Agents; Colitis, Ulcerative; Crohn Disease; Administration, Intravenous; Treatment Outcome; Adult; Randomized Controlled Trials as Topic; Remission Induction; Network Meta-Analysis; Maintenance Chemotherapy
PubMed: 38499736
DOI: 10.1007/s10620-023-08252-1