Publications by authors named "Douglas E Schlichting"
Article Synopsis
- The study evaluated the effectiveness of baricitinib in reducing pain for rheumatoid arthritis patients, focusing on those who used opioids and those who did not.
- Three phase 3 trials provided data comparing baricitinib at doses of 2 mg and 4 mg to placebo, with pain assessed through a visual analog scale over 24 weeks.
- Results showed that baricitinib significantly reduced pain for both opioid users and nonusers, while adalimumab did not show significant pain reduction in opioid users, highlighting the effectiveness of baricitinib in managing pain regardless of opioid use.
Article Synopsis
- - Juvenile idiopathic arthritis (JIA) is a common pediatric condition linked to uveitis, particularly in ANA-positive patients and those with oligoarticular arthritis, leading to chronic and potentially damaging eye inflammation.
- - A phase 3 clinical trial will evaluate the efficacy of Baricitinib, a JAK inhibitor, in treating JIA-associated uveitis, with a focus on patients who haven't responded to methotrexate but have not used biologics.
- - The trial will involve patients aged 2-18, comparing Baricitinib to Adalimumab, with the main goal being to assess patient response rates at 24 weeks, while also allowing for continued use of standard treatments. *
Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to be useful for COVID-19 infection via proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK.
View Article and Find Full Text PDFThe purpose of the study was to assess the proportion of patients who achieve pain relief thresholds, the time needed to reach the thresholds, and the relationship between pain and inflammation among patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate in RA-BEAM (NCT0170358). A randomized, double-blind trial was conducted, comparing baricitinib ( = 487), adalimumab ( = 330), and placebo ( = 488) plus methotrexate. Pain was evaluated by patient's assessment on a 0-100 mm visual analog scale (VAS).
View Article and Find Full Text PDFArticle Synopsis
- Cytokines play a crucial role in inflammatory diseases like rheumatoid arthritis (RA), and their dysregulation is a key aspect of the condition.
- Baricitinib, an oral JAK1 and JAK2 inhibitor, has emerged as an effective treatment option for a diverse group of RA patients.
- The review explores baricitinib's clinical effectiveness, safety, and its mechanism of action related to JAK/STAT signaling, while addressing the complexity of translating laboratory results into real-world clinical outcomes.
Objective: Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA). This study was undertaken to analyze changes in lymphocyte cell subsets during baricitinib treatment and to correlate these changes with clinical outcomes.
Methods: An integrated analysis was conducted by pooling data from 3 completed phase III trials comparing placebo with baricitinib treatment (RA-BEAM, RA-BUILD, and RA-BEACON) and 1 ongoing long-term extension study (RA-BEYOND) in patients with active RA (n = 2,186).
Effects of baricitinib on radiographic progression of structural joint damage at 1 year in patients with rheumatoid arthritis and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs.
RMD Open
May 2018
Background: Baricitinib was efficacious in a 24-week phase III study in patients with rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti rheumatic drugs (DMARDs) (csDMARDs) (RA-BUILD).
Objectives: To evaluate radiographic progression of structural joint damage in RA-BUILD patients over 48 weeks of baricitinib treatment in the long-term extension study, RA-BEYOND.
Methods: In RA-BUILD, patients were randomised to placebo, baricitinib 2 mg or 4 mg once daily, with rescue possible from week 16.
Objectives: Lipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.
Methods: Lipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study.
Objective: RA patients who have failed biologic DMARDs (bDMARDs) represent an unmet medical need. We evaluated the effects of baseline characteristics, including prior bDMARD exposure, on baricitinib efficacy and safety.
Methods: RA-BEACON patients (previously reported) had moderate to severe RA with insufficient response to one or more TNF inhibitor and were randomized 1:1:1 to once-daily placebo or 2 or 4 mg baricitinib.
Objective: To assess the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) up to 128 weeks in a phase IIb study (NCT01185353).
Methods: After a 24-week blinded period, eligible patients entered an initial 52-week open-label extension (OLE); patients receiving 8 mg once daily (QD) continued with that dose and all others received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at investigator discretion when ≥ 6 tender and ≥ 6 swollen joints were present.
Objective: To assess the effects of baricitinib on lipid profiles in patients with moderate-to-severe rheumatoid arthritis.
Methods: Treatment with once-daily doses of baricitinib (1, 2, 4, or 8 mg) or placebo was studied in 301 randomized patients. Changes in lipid profile and lipoprotein particle size and particle number were assessed at weeks 12 and 24, and associations with clinical efficacy were evaluated.
Objectives: To assess baricitinib on patient-reported outcomes (PROs) in patients with moderately to severely active rheumatoid arthritis, who had insufficient response or intolerance to ≥1 tumour necrosis factor inhibitors (TNFis) or other biological disease-modifying antirheumatic drugs (bDMARDs).
Methods: In this double-blind phase III study, patients were randomised to once-daily placebo or baricitinib 2 or 4 mg for 24 weeks. PROs included the Short Form-36, EuroQol 5-D, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment of pain, duration of morning joint stiffness (MJS) and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis.
Background: In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2 inhibitor, reduced disease activity in patients with rheumatoid arthritis who had not previously received treatment with biologic disease-modifying antirheumatic drugs (DMARDs).
Methods: In this phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to control type 1 error, were the American College of Rheumatology 20% (ACR20) response (primary end point), the Health Assessment Questionnaire-Disability Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score of 3.
Objectives: To investigate baricitinib (LY3009104, formerly INCB028050), a novel, oral inhibitor of JAK1/JAK2 in patients with moderate to severe rheumatoid arthritis (RA) despite treatment with methotrexate.
Methods: In this phase IIb study, 301 patients were randomised 2:1:1:1:1 to receive once daily doses of placebo or 1, 2, 4 or 8 mg baricitinib for 12 weeks. Patients assigned to 2, 4 and 8 mg baricitinib continued blinded treatment for an additional 12 weeks.
Elevated circulating endothelial cell (CEC) and circulating endothelial progenitor cell (CEPC) counts may indicate vascular damage and disease status, but data on these cell populations in patients with severe sepsis are limited. This study compared CEC and CEPC counts in patients with and without severe sepsis following intensive care unit (ICU) admission. Venous blood samples were collected within 24 h, 48-72 h, and 120-144 h.
View Article and Find Full Text PDFThe framework of equipoise has been promulgated as an underlying requirement for conducting ethical clinical research. Equipoise is the term used for a state of indifference about which treatment intervention or innovation will provide the most benefit and the least harm to recipients. Drawing on healthcare, research, and ethics literature, this paper analyses the implications of equipoise from the perspective of several proponents and critics.
View Article and Find Full Text PDFPurpose: The role of protein C in critical illness is assessed.
Summary: Conversion of protein C to activated protein C (APC) requires thrombin and thrombomodulin. When thrombin is not bound to thrombomodulin, it can convert fibrinogen to fibrin, factor V to factor Va, and factor VIII to factor VIIIa but will not convert protein C to APC.