THU0454 OA Pain Phenotypes Associated with Structural Progression and Change in Pain Over Time in Two Phase III Clinical Studies with Symptomatic Knee OA

2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 364.2-365
Author(s):  
A.R. Bihlet ◽  
A.-C. Bay-Jensen ◽  
M.A. Karsdal ◽  
I. Byrjalsen ◽  
B.J. Riis ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Phase Iii ◽  
Two Phase ◽  
Knee Oa ◽  
Structural Progression ◽  
Symptomatic Knee ◽  
Over Time

scholarly journals Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Bay-Jensen ◽  
Asger Bihlet ◽  
Inger Byrjalsen ◽  
Jeppe Ragnar Andersen ◽  
Bente Juhl Riis ◽  
...  
Keyword(s):  
Phase Iii ◽  
Response To Treatment ◽  
C Reactive Protein ◽  
Two Phase ◽  
Knee Oa ◽  
Reactive Protein ◽  
Inflammatory Phenotype ◽  
The Mean ◽  
Using Data

AbstractThe heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted in the field. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We investigated the level of blood CRPM in OA compared to RA using data from two phase III knee OA and two RA studies (N = 1591). Moreover, the association between CRPM levels and radiographic progression was investigated. The mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3–8.8] ng/mL, n = 781) compared to the RA patients (12.8 [9.5–16.0] ng/mL, n = 60); however, a significant subset of OA patients (31%) had CRPM levels (≥ 9 ng/mL) comparable to RA. Furthermore, OA patients (n = 152) with CRPM levels ≥ 9 ng/mL were more likely to develop contra-lateral knee OA assessed by X-ray over a two-year follow-up period with an odds ratio of 2.2 [1.0–4.7]. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.

scholarly journals Lipoprotein-Associated Phospholipase A2 (Lp-PLA2): A Novel and Promising Biomarker for Cardiovascular Risks Assessment

2013 ◽  
Vol 34 (5) ◽  
pp. 323-331 ◽  
Author(s):  
Anping Cai ◽  
Dongdan Zheng ◽  
Ruofeng Qiu ◽  
Weiyi Mai ◽  
Yingling Zhou
Keyword(s):  
Phospholipase A2 ◽  
Clinical Studies ◽  
Vascular Inflammation ◽  
Specific Inhibitor ◽  
Basic Research ◽  
Phase Iii ◽  
Cardiovascular Risks ◽  
Two Phase ◽  
Preclinical Trials ◽  
Risks Assessment

Atherosclerosis and its manifestations namely cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied, the residual cardiovascular (CV) risks are still very high. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Both pro-atherogenic property of Lp-PLA2and positive correlation with CV events have already been demonstrated by a large number of scientific and clinical studies. Currently, in the Adult Treatment Panel III (ATP III) guideline, Lp-PLA2has been recommended as an adjunct to traditional risk factors in assessing future CV risks. Encouragingly, darapladib, an orally Lp-PLA2specific inhibitor, has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA2in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA2, the actions of Lp-PLA2on atherosclerosis and the results of Lp-PLA2in scientific research and clinical studies.

scholarly journals Long-Term Use of Coagulation Factor IX (Recombinant) Albumin Fusion Protein (rIX-FP) in Previously Treated Patients with Hemophilia B in the Prolong-9FP Program

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1096-1096
Author(s):  
Aaron Lubetsky ◽  
Uri Martinowitz ◽  
Toshko Lissitchkov ◽  
Christine Voigt ◽  
Denise Wolko ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Phase Ii ◽  
Clinical Studies ◽  
Hemophilia B ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
On Demand ◽  
Clinical Program ◽  
Over Time

Abstract A fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin (rIX-FP) has been developed with an improved PK profile, improving hemophilia B treatment by allowing less frequent dosing than required with standard plasma-derived (pd) and recombinant (r) FIX products. The PROLONG-9FP clinical program has evaluated the use of rIX-FP for prophylaxis and on-demand treatment of bleeding in patients with severe hemophilia B. The clinical program is comprised of 5 clinical studies, including four completed studies (a Phase I pharmacokinetic (PK) study, a Phase II study, and two Phase III studies in adults and children), and an ongoing extension study, which includes previously untreated patients. Over 100 subjects from 42 hemophilia treatment centers in 12 countries have participated in the PROLONG-9FP clinical program. Here, we report on the long-term safety and efficacy of rIX-FP in 15 subjects who have continuously participated in 3 clinical studies (Phase II, Phase III and the on-going Phase III extension studies) over a period of 4 years. Subjects began either weekly prophylaxis treatment or on-demand treatment with rIX-FP in the Phase II 2004 study, and continued that treatment regimen in the Phase III 3001 study. The Phase III global study evaluated safety and efficacy of rIX-FP for prophylaxis treatment (PT) of every 7-, 10- and 14-days and on-demand treatment (ODT) of bleeding episodes. Subjects in the on-demand arm received only ODT for 6 months and then switched to 7-day PT. Subjects in the prophylaxis arm received 7-day PT for 6 months, and eligible subjects switched to 10- or 14-day PT interval. Upon completion of the 3001 study, subjects entered the on-going extension study 3003 and either continued the treatment regimen or switched to a longer prophylaxis interval of 10-, 14- or 21-days. Within subject comparisons of the annualized spontaneous bleeding rates (AsBR), total ABR over time and other efficacy parameters between regimens will be presented. Long-term use of rIX-FP is safe and well-tolerated. No subjects developed inhibitors to FIX or antibodies to rIX-FP during the 4 year treatment period, with a mean of 180 exposure days (EDs) for PT subjects and 125 EDs for ODT subjects. ABR decreased over time with rIX-FP prophylaxis, and longer treatment intervals were possible with no increase in consumption. Disclosures Lubetsky: CSL Behring: Consultancy. Martinowitz:CSL Behring: Honoraria, Speakers Bureau. Voigt:CSL Behring: Employment. Wolko:CSL Behring: Employment. Jacobs:CSL Behring: Employment. Santagostino:Biotest: Speakers Bureau; Kedrion: Speakers Bureau; Roche: Speakers Bureau; Octapharma: Speakers Bureau; Novo Nordisk: Speakers Bureau; Baxter/Baxalta: Speakers Bureau; Bayer: Speakers Bureau; Biogen/Sobi: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau.

Two phase III clinical studies of cevimeline for post-radiation xerostomia in patients with head and neck cancer

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 5503-5503 ◽  
Author(s):  
M. S. Chambers ◽  
M. R. Posner ◽  
C. U. Jones ◽  
R. S. Weber ◽  
R. Vitti
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Clinical Studies ◽  
Phase Iii ◽  
Two Phase ◽  
Post Radiation

scholarly journals Efficacy and Safety of Teneligliptin 40 mg in Type 2 Diabetes: A Pooled Analysis of Two Phase III Clinical Studies

2018 ◽  
Vol 9 (2) ◽  
pp. 623-636 ◽  
Author(s):  
Takashi Kadowaki ◽  
Kazuyo Sasaki ◽  
Manabu Ishii ◽  
Miyuki Matsukawa ◽  
Yoshiteru Ushirogawa
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Studies ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Two Phase

scholarly journals Blood levels of matrix metalloproteinase generated C-reactive protein metabolite (CRPM) are a sensitive measure of chronic inflammation in OA

2020 ◽  
Author(s):  
Anne-Christine Bay-Jensen ◽  
Asger Bihlet ◽  
Inger Byrjalsen ◽  
Jeppe R Andersen ◽  
Bente J Riis ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Phase Iii ◽  
Response To Treatment ◽  
Blood Levels ◽  
C Reactive Protein ◽  
Two Phase ◽  
Prognostic Effect ◽  
Knee Oa ◽  
Reactive Protein ◽  
Inflammatory Phenotype

Abstract BackgroundThe heterogeneous nature of osteoarthritis (OA) and the need to subtype patients is widely accepted. The biomarker CRPM, a metabolite of C-reactive protein (CRP), is released to the circulation during inflammation. Blood CRPM levels have shown to be associated with disease activity and response to treatment in rheumatoid arthritis (RA). We hypothesized that circulating levels of CRPMs could be used to identify OA patients with an inflammatory phenotype. We investigated the level and the prognostic effect of CRPM using combined data from two phase III OA and two RA studies (N = 1591). The association between serum CRPM levels and radiographic progression was investigated in knees of OA patients without radiographic OA in contra-lateral knee at baseline by dividing the patients into cases (knees with two-year radiographic progression) and controls (knees without radiographic progression). ResultsThe mean CRPM levels were significantly lower in OA (8.5 [95% CI 8.3-8.8] ng/mL) compared to the RA patients (15.6 [9.5-21.6] ng/mL); however, a significant subset of OA patients (31%) had CRPM levels ≥ 9ng/mL, as 75% of patients with early RA. Furthermore, OA patients with CRPM levels ≥ 9ng/mL were more likely to progress on X-ray over a two-year follow-up period; CRPM was prognostic for contralateral incidence knee OA with an odds ratio of 2.2 [1.0 - 4.7]. ConclusionA subset of OA patients, approximately 30%, appear to have tissue inflammation comparable to that of RA patients, reflected by the level of CRPM. Furthermore, high CRPM levels were prognostic of incident knee OA. These data suggest that CRPM is a blood-based biochemical marker for early identification OA patients with an inflammatory phenotype.

scholarly journals Association of Baseline Cardiovascular Diseases with 5-Year Knee and Hip Osteoarthritis Progression in Non-Obese Patients: Data from the KHOALA Cohort

2021 ◽  
Vol 10 (15) ◽  
pp. 3353
Author(s):  
Camille Roubille ◽  
Joël Coste ◽  
Jérémie Sellam ◽  
Anne-Christine Rat ◽  
Francis Guillemin ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Integrated Management ◽  
Hip Osteoarthritis ◽  
Secondary Outcome ◽  
Obese Patients ◽  
Radiological Progression ◽  
Knee Oa ◽  
Structural Progression ◽  
Symptomatic Knee ◽  
The Relationship

We aimed to explore the relationship between comorbidities and the structural progression in symptomatic knee and/or hip osteoarthritis (OA) patients. We analyzed the 5-year outcome of non-obese participants (body mass index (BMI) < 30 kg/m2) from the KHOALA cohort having symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) ≥ 2). The primary endpoint was radiological progression, defined as ΔKL ≥ 1 of the target joint at 5 years. The secondary outcome was the incidence of total knee or hip replacement over 5 years. Dichotomous logistic regression models assessed the relationship of comorbidities with KL progression and joint replacement while controlling for gender, age and BMI. Data from 384 non-obese participants were analyzed, 151 with hip OA and 254 with knee OA. At 5 years, cardiovascular diseases (CVD) were significantly associated with the 5-year KL change in both knee (OR = 2.56 (1.14–5.78), p = 0.02) and hip OA (OR = 3.45 (1.06–11.17), p = 0.04). No significant relationship was found between any type of comorbidities and knee or hip arthroplasty. This 5-year association between CVD and radiological progression of knee and hip OA in non-obese participants argue for an integrated management of CVD in knee and hip OA non-obese patients.

Sign in / Sign up

Export Citation Format

Share Document