HIKARI
ID: 59fb21b97aaac8114e2e5618
9 Documentos
Cerrar
9 Referencias ( articles) loading Revertir Estudificar

Estudio primario

No clasificado

Efficacy Confirmation Trial of CDP870 Without Coadministration of Methotrexate (MTX) in Japanese Rheumatoid Arthritis (RA)

Registro de estudios clinicaltrials.gov
Año 2008
Enlaces Registro de estudios
Cargando información sobre las referencias
The objectives of this study are to verify the superiority in efficacy (American College of Rheumatology 20%: ACR20) and investigate the pharmacokinetics and safety of CDP870 versus placebo without coadministration of MTX in active RA patients in whom MTX cannot be administrated.

Estudio primario

No clasificado

Long-term Treatment Study of Certolizumab Pegol Without Coadministration of Methotrexate in Japanese Rheumatoid Arthritis (RA) Patients

Autores Astellas Pharma Inc
Registro de estudios clinicaltrials.gov
Año 2009
Enlaces Registro de estudios
Cargando información sobre las referencias
The objectives of this study are to evaluate the safety and efficacy of certolizumab pegol when administered without coadministration of methotrexate over the long term in Japanese RA patients who transferred from Study 275-08-003 (NCT00791921), and to evaluate the effects of different dosing regimens on the safety and efficacy of certolizumab pegol in American College of Rheumatology 20% (ACR20) responders who completed Study 275-08-003.

Estudio primario

No clasificado

Certolizumab pegol improved physical function and heath related quality of life in patients with active rheumatoid arthritis who could not be treated with methotrexate: results form HIKARI study.

Revista Modern Rheumatology
Año 2012
Cargando información sobre las referencias

Estudio primario

No clasificado

Immunogenicity of certolizumab pegol without concomitant methotrexate and clinical response in rheumatoid arthritis patients: post-hoc analysis of the HIKARI study

Autores [No se listan los autores]
Revista
Año 2013
Enlaces DOI www.cochranelibrary.com
Cargando información sobre las referencias
Background Immunogenicity and subsequent reduction in clinical response is an issue for biological agents in rheumatoid arthritis (RA) treatment. Objectives To assess immunogenicity and clinical response to certolizumab pegol (CZP), a PEGylated Fc‐free anti‐TNF, in RA patients (pts) without concomitant methotrexate (MTX). Methods Post‐hoc analysis of a 24���wk, double‐blind (DB) study of CZP 200mg without concomitant MTX (HIKARI study) and subsequent open‐label extension (OLE) in Japanese pts with active RA (116 pts).1 Results Anti‐CZP antibodies (Abs) were detected in 18 pts (15.5%) at any visit during the first 24 wks. Two anti‐CZP profiles were observed: 1) Abs peaked between Wk8‐Wk12 (early development, n=7); 2) Abs peaked at/after Wk24 (late development, n=11) (Figure). In 6 pts with early development, anti‐CZP Abs decreased to below threshold (<=2.4units/mL) at Wk24, and their plasma CZP level increased at Wk24 (median CZP concentration of 7.7mug/ml), following a drop at Wk8 (35.3 and 2.2mug/ml at Wk6 and Wk8, respectively). In contrast, in pts with late development, Abs appeared mostly at Wk24, and plasma CZP level slowly decreased from Wk8 (median CZP concentrations 27.5 and 2.4mug/ml at Wk8 and Wk24, respectively). ACR20/ACR50/ACR70 responses of early development pts (n=7) were greater than those with late development (n=11) (Table). These results suggest that early, transient development of anti‐CZP Abs was not associated with poor long‐term clinical response, whereas later development led to loss of response. This observation suggests that when anti‐CZP Abs with low affinity to CZP are developed early, they may be adsorbed by the high level of plasma CZP. In contrast, late‐developed anti‐CZP Abs may reside longer and lead to sustained drug clearance, similar to Abs against other anti‐TNF biologics. Conclusions Anti‐CZP Abs were detected in 15.5% of RA pts during 24 wks of treatment without concomitant MTX. Better long‐term clinical responses were observed in patients with early vs late anti‐CZP Abs development. (Table Presented).

Estudio primario

No clasificado

Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in patients with rheumatoid arthritis: a report from the Japan College of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs

Revista Modern rheumatology
Año 2013
Enlaces Pubmed DOI www.cochranelibrary.com
Cargando información sobre las referencias
Objective: The associations between elevated levels of serum Krebs von den Lungen‐6 (KL‐6) and treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) inhibitors were investigated in five Japanese clinical trials. Methods: Percentages and incidence rates were calculated for elevated serum KL‐6 levels. Adverse events associated with elevated levels of serum KL‐6 were investigated. Results: In RISING, a clinical trial for infliximab, 15.6 % of the enrolled patients met criterion B (KL‐6 >500 U/ml and < 1.5‐fold increase over the baseline value) by week 54. In HIKARI, 7.8 % of the certolizumab pegol (CZP) group and 0 % of the placebo group met criterion B during the double‐blind (DB) period (p = 0.003). In J‐RAPID, 8.4 % of the methotrexate (MTX) + CZP and 3.9 % of the MTX + placebo groups met criterion B during the DB period. In GO‐MONO, 1.8 % of the golimumab (GLM) and 1.3 % of the placebo groups met criterion B during the DB period. In GO‐FORTH, 7.1 % of the MTX + GLM and 0 % of the MTX + placebo groups met criteron B during the DB period (p = 0.017). No adverse events accompanied the elevation of serum KL‐6 levels in 95.7 % of these patients. Conclusion: Serum KL‐6 levels may increase during anti‐ TNF therapy without significant clinical events. In these patients, continuing treatment with TNF inhibitors under careful observation is a reasonable option. Japan College of Rheumatology 2012.

Estudio primario

No clasificado

Improved physical function, pain, and health related quality of life with certolizumab pegol in japanese rheumatoid arthritis patients without methotrexate co-administration: Results from the hikari study

Conferencia Annals of the Rheumaic Diseases
Año 2013
Enlaces DOI
Cargando información sobre las referencias
Background Physical function, pain and health-related quality of life (HRQoL) are important outcomes in RA. The HIKARI study examined the efficacy and safety of certolizumab pegol (CZP) in Japanese patients (pts) with active RA in whom methotrexate (MTX) could not be administered.1 Objectives To assess the impact of CZP on physical function, pain and HRQoL in the HIKARI study. Methods In this 24-week (Wk), Phase III, double-blind, randomized, placebo-controlled study, pts were randomized to CZP 200 mg (following induction dosing of 400 mg at Wks 0, 2, and 4) or placebo (PBO) every 2 Wks. Concomitant DMARDs other than MTX were permitted. Pts not achieving ACR20 at Wks 12 and 14 withdrew at Wk 16 and were eligible to enter an open-label extension, as were pts completing the study. Primary efficacy endpoint was ACR20 at Wk 12. Physical function was assessed with HAQ-DI and pain with VAS at each visit. HRQoL was evaluated with SF36 at Wks 12 and 24. ACR responses were assessed using NRI, and HAQ-DI, pain (VAS) and SF36 using LOCF. Results A total of 230 pts were randomized. Demographic and baseline characteristics were similar between CZP and PBO groups: mean RA disease duration was 5.4 and 5.8 years, mean HAQ-DI 1.05 and 1.21, and mean DAS28(ESR) 6.09 and 6.30, respectively. ACR20 response rates at Wk 12 in CZP and PBO groups were 67.2% and 14.9% (p<0.001) and at Wk 24 were 63.8% and 11.4% (p<0.001); ACR50 and ACR70 response rates were also significantly higher in the CZP group than in the PBO group at Wk 12 (ACR50: 37.9% vs 6.1%; ACR70:19.0% vs 0%) and Wk 24 (ACR50: 46.6% vs 6.1%; ACR70: 25.9% vs 0.9%). As early as Wk 1 HAQ-DI was improved in the CZP group compared to PBO; HAQ-DI change from baseline at Wk 1 was -0.30 in CZP group vs -0.01 in PBO group (p<0.001). At Wk 24 HAQ-DI change from baseline was -0.48 in CZP group vs 0.12 in PBO group (p<0.001). Pain (VAS) was also significantly improved; change from baseline at Wk 1 was -18.9 in CZP group vs -2.2 in PBO group, and at Wk 24 was -27.5 in CZP group vs -1.2 in PBO group (p<0.001 at both timepoints). CZP showed significantly greater improvements in both the physical and the mental components of the SF36 than PBO at Wks 12 and 24. Changes in physical and mental component summary scores from baseline at Wk 24 were 9.27 in CZP group vs -1.46 in PBO group (p<0.001), and 5.24 in CZP group vs -0.94 in PBO group (p<0.001). Conclusions Treatment with CZP resulted in a rapid and sustained reduction in RA signs and symptoms, and improved physical function and HRQoL in Japanese RA patients who could not be treated with MTX.

Estudio primario

No clasificado

Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: the HIKARI randomized, placebo-controlled trial.

Revista Modern rheumatology
Año 2014
Enlaces Pubmed DOI
Cargando información sobre las referencias
OBJECTIVE: This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered. METHODS: A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks. RESULTS: ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm. CONCLUSION: CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression.

Estudio primario

No clasificado

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of the HIKARI study.

Revista Modern rheumatology
Año 2014
Enlaces Pubmed DOI
Cargando información sobre las referencias
OBJECTIVES: To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients who could not receive methotrexate (MTX). METHODS: HIKARI double-blind (DB) patients were entered into an open-label extension (OLE) study. Patients withdrawn at 16 weeks due to lack of efficacy and DB completers without a 24-week American College of Rheumatology (ACR)20 response received CZP 200 mg every 2 weeks (Q2W). DB completers with 24-week ACR20 responses were randomized to CZP 200 mg Q2W or CZP 400 mg every 4 weeks. RESULTS: The ACR20/ACR50/ACR70 response rates of DB completers (n = 98) were 82.7%/56.1%/34.7% at OLE entry, and 83.7%/65.3%/48.0% at 52 weeks, respectively. Other clinical, functional, and radiographic outcomes were sustained during long-term administration of CZP, even without MTX. No new unexpected adverse events were observed during long-term CZP treatment. The efficacy and safety of CZP treatment were similar between the two dosing schedules. CONCLUSIONS: Long-term CZP administration is efficacious and safe for RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules. The choice between two maintenace regimens adds flexibility in administration schedules for RA patients and physicians.

Estudio primario

No clasificado

Better clinical responses seen early with the loading dose of certolizumab pegol are maintained until one year

Revista Annals of the Rheumatic Diseases
Año 2014
Enlaces DOI http://ard.bmj.com/content/73/Suppl_2/247.1.abstract
Cargando información sobre las referencias
Background Certolizumab pegol (CZP) has demonstrated rapid and sustained improvements in disease activity in Japanese patients (pts) with active rheumatoid arthritis (RA), both with methotrexate (J-RAPID; NCT00791999) and with or without DMARDs other than methotrexate (HIKARI; NCT00791921) in placebo-controlled double-blind (DB) randomized trials.1,2 Although previous analysis suggested that the loading dose (LD) of CZP (400mg at Weeks (Wks) 0, 2 and 4) improves the clinical response of CZP for the first 24 wks3, the impact of the initial LD on the long-term outcomes remains unknown. Objectives To compare the safety, efficacy and immunogenicity 1 year (yr) after initiation of CZP with and without the LD. Methods Data from the Japanese clinical trials1,2 and the respective open-label extensions (OLEs) (J-RAPID OLE: NCT00851318; HIKARI OLE: NCT00850343)4,5 were used for this analysis. Pts randomized to receive CZP 200mg every 2 wks (Q2W) with the LD were defined as LD groups (J-RAPID: n=82; HIKARI: n=116), whereas pts randomized to receive placebo in the DB trials who entered the respective OLEs and initiated CZP 200mg Q2W without LD were defined as No-LD groups (J-RAPID: n=61; HIKARI: n=99). The ACR response rates, achievement of DAS28 LDA, safety assessments, plasma CZP levels and rates of anti-CZP antibodies (Abs) were analyzed up to 1yr after initiating CZP. DB baseline for the LD groups and at OLE entry for the No-LD groups were used as the baselines. Results The ACR20/50/70 responses of the LD vs No-LD groups in J-RAPID were 74.4%/62.2%/32.9% vs 76.8%/60.7%/26.8%, and in HIKARI were 69.0%/50.9%/31.9% vs 62.1%/43.2%/23.2%, respectively, at 1yr (Figure). The LD groups had higher proportion of pts in DAS28 LDA (J-RAPID: 48.8% vs 42.6%; HIKARI: 42.2% vs 26.3%). Frequency of anti-CZP Abs was lower in the LD groups than in the No-LD groups (J-RAPID: n=2/82 [2.4%] vs n=4/61 [6.6%]; HIKARI: n=30/116 [25.9%] vs n=32/99 [32.3%]). Pts who developed anti-CZP Abs had lower plasma CZP levels and lower clinical responses than Ab-negative pts. Safety profiles were similar between the groups. (Figure presented) Conclusions While this post-hoc analysis has limitations including the comparison of DB vs OLE data, the results suggest that the benefits potentially due to the initial loading dose are sustained until at least 1yr without additional risk of adverse events.