AI Article Synopsis
- The study investigates dose escalation patterns in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC), using systematic literature reviews to gather data.
- Researchers found that most studies followed initial maintenance doses according to local regulations, but notable deviations occurred, especially for ustekinumab usage in non-North America (ONA) regions.
- The findings highlight a variety of dose escalation patterns, indicating that while some follow guidelines, others suggest escalating doses more frequently than recommended.
Article Abstract
Introduction: Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC.
Methods: Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Embase, and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]).
Results: Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies (n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks.
Conclusion: Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation.
Prospero Registration: CRD42021289251.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10129944 | PMC |
| http://dx.doi.org/10.1007/s12325-023-02457-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age.
Mol Ther
January 2025
Academic Unit of Ophthalmology, Translational Health Sciences, University of Bristol, Bristol, BS8 1TD, UK; NIHR Biomedical Research Centre of Ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK. Electronic address:
Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.
View Article and Find Full Text PDFIntratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial.
J Immunother Cancer
January 2025
Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China
Background: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients.
Methods: This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment.
Spontaneous oxycodone withdrawal disrupts sleep, diurnal, and electrophysiological dynamics in rats.
PLoS One
January 2025
Dept. of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, United States of America.
Opioid dependence is defined by an aversive withdrawal syndrome upon drug cessation that can motivate continued drug-taking, development of opioid use disorder, and precipitate relapse. An understudied but common opioid withdrawal symptom is disrupted sleep, reported as both insomnia and daytime sleepiness. Despite the prevalence and severity of sleep disturbances during opioid withdrawal, there is a gap in our understanding of their interactions.
View Article and Find Full Text PDFSubgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist.
Diabetes Obes Metab
January 2025
Boehringer Ingelheim International GmbH, Biberach, Germany.
Aim: To explore the effects of sex and baseline body mass index (BMI) on the efficacy and safety of survodutide in people with a BMI ≥27 kg/m.
Materials And Methods: Totally 387 people (aged 18-75 years, BMI ≥27 kg/m, without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.
A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
Cancer Chemother Pharmacol
January 2025
Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!