Background: The advent of biosimilars may increase the frequency of dose escalation with biologics in psoriasis.
Objective: To explore the frequency and outcomes of dose escalation with adalimumab etanercept, and ustekinumab.
Methods: Data were extracted from DermaReg-Pso, a psoriasis register in Stockholm, Sweden. The main exposure was treatment, and the main outcome was dose escalation. We describe outcomes with dose escalation by estimating drug survival and changes in the Psoriasis Area and Severity Index (PASI).
Results: 554 patients had 946 treatment episodes with adalimumab, etanercept, or ustekinumab. The cumulative incidence of dose escalation was 4.1 per 100 treatment years. The Hazard Ratios (HRs) for dose escalation with ustekinumab vs adalimumab and ustekinumab vs etanercept were 1.93 (95% CI: 1.25-2.98), and 2.20 (95% CI: 1.42-3.41), respectively. After dose escalation, the HRs for treatment discontinuation with adalimumab and etanercept compared with ustekinumab were 3.10 (95% CI: 1.56-6.18) and 7.15 (95% CI: 3.96-12.94), respectively. PASI was higher after compared to before dose escalation for etanercept ( = 0.036), but not for adalimumab ( = 0.832) or ustekinumab ( = 0.300).
Conclusions: Dose escalation was comparatively more frequent with ustekinumab than with adalimumab or etanercept; however, treatment discontinuation after dose escalation was more common with adalimumab and etanercept than ustekinumab.
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http://dx.doi.org/10.1080/09546634.2024.2398170 | DOI Listing |
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 PDFJ 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.
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 PDFDiabetes 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.
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.
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