This is a Phase IIIb multicenter study to evaluate the safety and efficacy of certolizumab pegol (CZP) administered to patients with moderate-to-severe rheumatoid arthritis.
INTERVENTION: Product Name: certolizumab pegol Product Code: CDP870 Pharmaceutical Form: Solution for injection INN or Proposed INN: certolizumab pegol Current Sponsor code: CDP870 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: Rheumatoid arthritis ; MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis PRIMARY OUTCOME: Main Objective: To assess the clinical response rate as measured by American College of Rheumatology 20% (ACR20) response rate at Week 12. Primary end point(s): The primary efficacy variable is the ACR 20 (American College of Rheumatology 20% response criteria) responder rate at Week 12.; ; Safety variables to be assessed are adverse events, vital signs, physical examination (including symptoms of active tuberculosis), and measurements of laboratory parameters.; ; Clinical laboratory values (hematology, serum biochemistry, and urinalysis) will be collected and assessed. Secondary Objective: • To assess:; ‐ for all patients at Week 12, and every 8 weeks and at the completion/withdrawal visit in the group remaining in the study after Week 12: ; ‐ clinical response rate.; ‐ reduction of disease activity.; ‐ achievement of clinical remission.; ‐ additionally, at Week 12:; ‐ improvement in individual components of the ACR criteria; ‐ Time to sustained ACR20 response. ; ‐ European League Against Rheumatism (EULAR) response.; ‐ additionally, every 8 weeks and at completion/withdrawal visit :; ‐ change from Baseline in individual components of the ACR criteria.; ; • Tolerability and safety of CZP therapy over the first 12 weeks of treatment and over the open‐label treatment extension period.; ; • To evaluate the influence of some characteristics (as per protocol) on ACR20 response rate at Week 12 and adverse events rate with CZP therapy INCLUSION CRITERIA: 1. Patients must be at least 18 years old at the screening visit. 2. Patients must be able to understand the information provided to them and to give written Informed Consent. 3. Female patients must be either postmenopausal for at least one year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence only is not an acceptable method. Patients must agree to use adequate contraception during the study and for 12 weeks after their last dose of CZP. Male patients must agree to ensure they or their female partner(s) uses adequate contraception during the study and for 12 weeks after the patient receives their last dose of CZP. 4. Patients must have a diagnosis of adult–onset RA of at least three months duration as defined by the 1987 American College of Rheumatology classification criteria.<b
OBJETIVO: Investigar la eficacia y seguridad de certolizumab pegol (CZP) en una amplia población de pacientes con artritis reumatoide activa.
MÉTODOS: En este 12 semanas de duración, período doble ciego del ensayo de fase IIIb, los pacientes con AR con respuesta inadecuada a al menos un DMARD fueron aleatorizados 4:1 a CZP (400 mg en las semanas 0, 2 y 4, seguido de 200 mg cada 2 semanas) o placebo (cada 2 semanas), además de la terapia actual estratificada por anterior uso de inhibidores de TNF, el uso concomitante de metotrexato y la duración de la enfermedad (<2 vs ≥ 2 años). El resultado primario fue la tasa de respuesta ACR20 en la semana 12.
Resultados: De 1.063 pacientes (CZP = 851; placebo = 212), el 37,6% tenían anterior uso de inhibidores de TNF. Línea de base significa Índice HAQ Discapacidad (HAQ-DI) y DAS 28-conjunta de evaluación-ESR [DAS28 (ESR)] los valores fueron de 1,5 y 6,4 en el grupo de CZP, y 1,6 y 6,4 en el grupo placebo, respectivamente. El objetivo primario fue significativa (semana 12 ACR20, CZP vs placebo: 51,1 vs 25,9%, p <0,001); se observaron diferencias en la semana 2 (31,8 vs 8,5%, P <0,001). HAQ-DI y DAS28 (ESR) cambio desde el inicio y ACR50 fueron significativos desde la semana 2. Semana 12 respuestas ACR20 fueron similares en todos los subgrupos de pacientes CZP independientemente del uso concomitante DMARD al inicio del estudio. Eventos adversos graves y adversos fueron comparables entre CZP y placebo, sin nuevas señales de seguridad.
CONCLUSIÓN: CZP se asoció con respuestas clínicas rápidas y consistentes y la mejora de la función física en un grupo diverso de pacientes con AR, independientemente de la terapia concomitante o anterior.
JUICIO DE INSCRIPCIÓN: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00717236.
INTRODUCTION: The effect of certolizumab pegol (CZP) on patient-reported outcomes (PROs) was investigated in 1063 patients with rheumatoid arthritis (RA) from the REALISTIC trial (double-blind, placebo-controlled to week 12, open-label to week 28; randomized 4:1 [CZP:placebo]). Correlations between PROs and RA signs and symptoms, and the relative efficacy of these measures, were examined.
METHODS: Adults with RA and an inadequate response to at least one disease-modifying antirheumatic drug were enrolled. PROs assessed included physical function (using the Health Assessment Questionnaire-Disability Index), pain, fatigue, sleep disturbance, Patient Global Assessment of Disease Activity (PtGA), Routine Assessment of Patient Index Data 3 (RAPID3), and Rheumatoid Arthritis Disease Activity Index (RADAI).
RESULTS: Early significant and clinically meaningful improvements in all PROs were observed to week 12 with CZP vs. placebo and were maintained to the end of the trial (week 28). At week 12, up to one-third more CZP patients showed improvements compared with placebo that were greater than or equal to the minimal clinically important difference (MCID) in fatigue, sleep problems, pain, PtGA, RADAI, and RAPID3. The changes in PROs were correlated with clinical measures of disease activity, including the Disease Activity Score in 28 joints using C-reactive protein as well as tender and swollen joint counts.
CONCLUSIONS: Rapid improvements in PROs were seen in patients with RA treated with CZP. The magnitude of improvement exceeded the MCID in multiple domains and demonstrated that CZP improves aspects of health-related quality of life that are meaningful to patients and superior to placebo. PROs provide information complementary to clinical outcomes in assessment of treatment benefits.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00717236 . Registered on 15 July 2008.
INTRODUCTION: This 28-week, phase IIIb study assessed safety and maintenance of response to certolizumab pegol (CZP) in a diverse population of rheumatoid arthritis (RA) patients, stratified by prior anti-TNF exposure, concomitant methotrexate (MTX) use and disease duration. The ability to predict achievement of low disease activity (LDA) at week 28 from improvements in Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) and Clinical Disease Activity Index (CDAI) up to week 12 was assessed.
METHODS: The 28-week study population included all patients who completed the double-blind (DB) phase and entered the open-label (OL) phase, receiving 200 mg CZP every 2 weeks (Q2W) ≥16 weeks. In the 12-week DB period, patients with active RA and an inadequate response to ≥1 disease-modifying antirheumatic drug (DMARD) were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4 then 200 mg Q2W) or placebo (Q2W), stratified by prior anti-TNF use, concomitant use of MTX and disease duration (<2 years vs. ≥2 years).
RESULTS: A total of 955 patients entered the OL phase. At week 28, similar clinical improvements were seen in those receiving CZP throughout (CZP → CZP; n = 771) and those receiving placebo during the DB phase and switching to CZP in the OL phase (placebo → CZP; n = 184) (ACR20 response rate = 59.7% vs. 53.3%; ACR50/ACR70 response rates were also similar). Effect of CZP treatment was similar regardless of prior anti-TNF use, disease duration and concomitant DMARDs, based on ACR20 response rates. The percentage of patients achieving DAS28(ESR) LDA at week 28 was calculated for DAS28(ESR), SJC or CDAI responders at earlier time points. Reductions from baseline (Δ) of DAS28(ESR) <1.2, ΔSJC <25% or ΔCDAI <10 by week 12 were associated with <9% chance of achieving LDA at week 28 regardless of prior anti-TNF exposure. Adverse event rates were similar for placebo → CZP and CZP → CZP patients, with no new safety signals identified.
CONCLUSIONS: A diverse population of RA patients with varying disease duration showed rapid and sustained clinical improvements on CZP treatment, regardless of prior anti-TNF or concomitant DMARD use. Failure to achieve improvements in DAS28(ESR), SJC or CDAI within the first 12 weeks of CZP therapy was associated with a low chance of achieving LDA at week 28. No new safety signals were observed.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00717236 , 15 July 2008.
This is a Phase IIIb multicenter study to evaluate the safety and efficacy of certolizumab pegol (CZP) administered to patients with moderate-to-severe rheumatoid arthritis.
País»Canada,France,Germany,Italy,Netherlands,Spain,United States
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
