Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease ...(IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1-10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10-15 μg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti-tumor necrosis factor therapy. It was recommended to perform proactive TDM after induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti-tumor necrosis factors.
The goal of therapeutic drug monitoring (TDM) is to optimize anti-TNF (tumor necrosis factor) biologic treatment in patients with inflammatory bowel disease (IBD). Although commercial assays are ...readily available for both ustekinumab and vedolizumab, the use of TDM with these newer biologic medications is at its infancy. The clinical utility of TDM with non-anti-TNF mechanisms of action is not clear. This review summarizes the latest available data on the pharmacokinetics of newer biologic and oral small molecules and highlights the threshold concentrations that have been associated with improved outcomes in IBD patients.
Ustekinumab Safety in Pregnancy: A Comprehensive Review Gorodensky, Jonah H.; Bernatsky, Sasha; Afif, Waqqas ...
Arthritis care & research (2010),
April 2023, 2023-04-00, 20230401, Letnik:
75, Številka:
4
Journal Article
Recenzirano
Chronic inflammatory conditions, including inflammatory bowel diseases (IBD), psoriasis, and psoriatic arthritis, are prevalent among women of reproductive age; patients with active disease during ...pregnancy may be at an increased risk of adverse birth outcomes. For this reason, physicians are focused on approaches to controlling disease activity prior to and during pregnancy. The safety profile of many therapies used for these conditions has been relatively well established, though evidence on newer therapies is lacking. Ustekinumab is a relatively new interleukin‐12/23 inhibitor approved for IBD, psoriasis, and psoriatic arthritis, whose safety in pregnancy is not yet fully understood. In this comprehensive review, we critically assess the available evidence on ustekinumab in pregnancy across animal studies and human case reports, case series, observational studies, and clinical practice guidelines. We show that, to date, studies have not identified an excess risk of adverse pregnancy outcomes among women exposed to ustekinumab in pregnancy, with few exposed pregnancies and potential for some bias. Clinical guidelines are conflicted regarding whether they recommend continuing or discontinuing ustekinumab, highlighting the paucity of data and need for more research on this issue.
Background & Aims The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian ...consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. Methods A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists. Results The participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti–tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. Conclusions Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.
Background and Objectives
Rare but potentially life‐threatening hypersensitivity reactions can occur during the administration of intravenous iron. To provide guidance to healthcare professionals ...caring for adults receiving intravenous iron, a panel of 10 Canadian clinical experts developed a practical algorithm for the identification and management of hypersensitivity reactions to intravenous iron.
Materials and methods
A systematic search of PubMed to February 2018 was performed. Articles related to hypersensitivity reactions were selected for review. The algorithm was developed during a 1‐day live meeting based on the literature review and clinical expertise where evidence was lacking. The algorithm was then refined through an iterative process involving a web‐based platform and virtual meetings.
Results
The algorithm provides guidance to healthcare professionals in preparing for and administering IV iron, as well as recognizing and managing hypersensitivity reactions to intravenous iron. Considerations for re‐challenging patients who have experienced prior reactions are provided.
Conclusion
Healthcare professionals who are involved in the care of patients receiving intravenous iron should be trained to anticipate, recognize and manage hypersensitivity reactions to intravenous iron to optimize patient care.
Abstract
Background and Aims
The UNIFI long-term extension LTE study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy.
Methods
Patients ...randomised to ustekinumab every 12 weeks q12w or every 8 weeks q8w at maintenance baseline N = 348 and randomised ustekinumab-treated patients in the LTE N = 284 were evaluated. Symptomatic remission Mayo stool frequency = 0/1, rectal bleeding = 0 was assessed. Safety included all LTE patients N = 188 placebo and N = 457 ustekinumab.
Results
Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma BCC reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes.
Conclusions
Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed.
Graphical Abstract
Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients ...with UC through 4 years.
Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks q8w or q12w or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200.
Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% 117/174) were in symptomatic remission than those with a history of biologic failure (41.6% 67/161). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events.
The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.
Summary
Background
Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the ...effectiveness of dose‐optimisation for ustekinumab nonresponse is limited.
Aim
To assess the effectiveness of dose escalation of ustekinumab.
Methods
This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.
Results
A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.
Conclusions
Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.
Abstract
Background
Fistulas occur in about 25% of patients with Crohn's disease (CD) and can be difficult to treat. The aim of this consensus was to provide guidance for the management of patients ...with perianal fistulizing CD.
Methods
A systematic literature search identified studies on the management of fistulizing CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform using a modified Delphi process, then finalized, and voted on by a group of specialists.
Results
The quality of evidence for treatment of fistulizing CD was generally of very low quality, and because of the scarcity of good randomized controlled trials (RCTs), these consensus statements generally provide conditional suggestions (5 of 7 statements). Imaging and surgical consultations were recommended in the initial assessment of patients with active fistulizing CD, particularly those with complicated disease. Antibiotic therapy is useful for initial symptom control. Antitumor necrosis factor (anti-TNF) therapy was recommended to induce symptomatic response, and continued use was suggested to achieve and maintain complete remission. The use of concomitant immunosuppressant therapies may be useful to optimize pharmacokinetic parameters when initiating anti-TNF therapy. When there has been an inadequate symptomatic response to medical management strategies, surgical therapy may provide effective fistula healing for some patients.
Conclusions
Optimal management of perianal fistulizing CD requires a collaborative effort between gastroenterologists and surgeons and may include the evidence-based use of existing therapies, as well as surgical assessments and interventions when needed.
10.1093/ibd/izy247_video1
izy247.video1
5978518763001
Background
Reactivation of LTBI in patients with IBD on anti-TNF-α agents can lead to serious life-threatening illness. No gold standard exists for the detection of LTBI. We examined whether a dual ...testing strategy with TST and IGRA would improve the detection of LTBI.
Methods
Consecutive IBD patients being considered for anti-TNF-α treatment underwent testing with a TST, IGRA and CXR. All patients completed a self-administered questionnaire. The association of both tests with demographic factors, LTBI risk factors, BCG vaccination, IS therapy and agreement between the TST and IGRA were evaluated.
Results
One-hundred and fifty-five IBD patients were included, 6% were TST positive and 5% were IGRA positive. Concordance between TST and IGRA was fair (
κ
= 0.21, 95% CI − 0.081–0.498). Neither test was affected by age, gender or BCG vaccination. The presence of risk factors for LTBI was found to be positively associated with TST (OR 19.8, 95% CI 3.9–102.1), but not IGRA. IGRA was negatively associated with IS therapy (OR 0.06, 95% CI 0.007–0.5), but not TST. Four patients who were IGRA positive but TST negative were treated for LTBI by a respirologist.
Conclusion
An IGRA result was negatively associated with IS therapy, while the presence of risk factors for LTBI was found to be positively associated with TST results. There was fair agreement between positive TST and IGRA results. The addition of IGRA to the standard practice of TST and CXR increased the number of cases that were initiated on LTBI therapy.
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