IMPROVED (Induction therapy with MTX and Prednisone in Rheumatoid Or Very Early arthritic Disease - EudraCT 2006-006186-16)
ID: 59f1f2516ec0d60eea67abb1
8 Documentos
Cerrar
8 Referencias ( articles) loading Revertir Estudificar

Estudio primario

No clasificado

Induction therapy with methotrexate and prednisone in rheumatoid or very early arthritic disease

Registro de estudios ISRCTN registry
Año 2006
Enlaces DOI isrctn.com
Cargando información sobre las referencias
There is a clinically and statistically significant difference in the percentage of patients who achieve and maintain clinical remission (defined as Disease Activity Score [DAS] less than 1.6) and in functional ability and progression of radiological joint damage after one year of follow-up in recent-onset arthritis patients (Rheumatoid Arthritis [RA] and Undifferentiated Arthritis [UA]) who, having failed to achieve remission on a combination of methotrexate and a tapered high dose of prednisone, receive extended medication in a combination of methotrexate, sulphasalazine, hydroxychloroquine and low dose prednisone, or who switch to a combination of methotrexate and adalimumab.

Estudio primario

No clasificado

IMPROVED: Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease

Registro de estudios EU Clinical Trials Register
Año 2007
Enlaces EUCTR - NL
Cargando información sobre las referencias
INTERVENTION: Product Name: Methotrexate Product Code: MTX Pharmaceutical Form: Tablet INN or Proposed INN: METHOTREXATE CAS Number: 59052 Current Sponsor code: MTX Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 30‐ Product Name: Prednisone Pharmaceutical Form: Tablet INN or Proposed INN: PREDNISONE CAS Number: 53032 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 7,5‐60 Product Name: Sulfasalazine Pharmaceutical Form: Tablet INN or Proposed INN: SULFASALAZINE CAS Number: 599791 Current Sponsor code: SSZ Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 2000‐ Trade Name: hydroxychloroquine Product Name: hydroxychloroquine Product Code: HCQ Pharmaceutical Form: Tablet INN or Proposed INN: HYDROXYCHLOROQUINE SULFATE CAS Number: 747364 Current Sponsor code: HCQ Concentration unit: mg milligram(s) Concentration type: up to Concentration number: 400‐ Trade Name: Humira Product Name: adalimumab Pharmaceutical Form: Solution for injection CONDITION: rheumatoid arthritis and undifferentiated arthritis ; MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis PRIMARY OUTCOME: Main Objective: The objectives of this study are:; •To determine the percentage of patients with recent‐onset RA and UA who achieve and maintain clinical remission on treatment with a combination of methotrexate 25 mg/week and extended prednisone pulse (tapered high dose) after 4 months. ; ; •To determine whether, if clinical remission is not achieved, methotrexate+prednisone combination therapy should be extended with sulphasalazine and hydroxychloroquine or switched to methotrexate+adalimumab combination therapy. ; Primary end point(s): Clinical remission according to a disease activity score (DAS) < 1.6, measured by research nurses at each follow‐up visit. The percentage of patients achieving clinical remission after 4 months with the initial therapy consisting of MTX and tapered high dose prednisone will be calculated. From the patients who were randomized to one of two treatment arms, the percentage achieving clinical remission after one year will be calculated. ; ; Functional ability will be measured by the Dutch Health Assessment Questionnaire (HAQ), a self‐administered questionnaire that evaluates the level of difficulty the patient is experiencing with activities of daily living (ADL) and the degree of assistance required by the patient. ; ; Radiological joint damage, absolute as well as progression from baseline, will be assessed on radiog¬raphs of the hands, wrists and feet at entry and one year later by the validated modified Sharp/van der Heijde score All radio¬graphs will be sent to the coordi¬na¬ting centre and viewed separate by two experienced rheumatologists, who are blinded for the treatment allocation. The radiographs will be presented in random order.; Secondary Objective: toxicity, costs, quality of life measurements INCLUSION CRITERIA: 1. minimum age of 18 years 2. at least one swollen joint 3. at least one other painful joint 4. symptom duration shorter than 2 years 5. diagnosis rheumatoid arthritis according to the ACR classification criteria or 6. diagnosis undifferentiated arthritis, suspected for rheumatoid arthritis by the rheumatologist, as no classification criteria exist. 7. patients naive for treatment with corticosteroids and disease modifying anti‐rheumatic drugs (DMARDs). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range

Estudio primario

No clasificado

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study.

Revista Arthritis research & therapy
Año 2013
Enlaces Pubmed DOI PubMed Central
Cargando información sobre las referencias
INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-16.

Estudio primario

No clasificado

OP0182 Drug Free Remission After One Year of Treatment in Patients with Early Rheumatoid Arthritis: Also Possible for ACPA Positive Patients?

Revista Annals of the Rheumatic Diseases
Año 2013
Enlaces DOI
Cargando información sobre las referencias
Background In rheumatoid arthritis (RA) remission is a realistic treatment goal. Is tapering medication to drug free remission (DFR) possible for all patients? Objectives To assess which patients with early (rheumatoid) arthritis achieve DFR after one year (DFR1year) of early remission induction therapy. Methods By protocol of the IMPROVED study, patients who achieved remission (DAS&amp;lt;1.6) after 4 months (early remission, n=375) of combination therapy with methotrexate 25 mg/wk and a tapered high dose of prednisone (60 mg/day tapered in 7 weeks to 7.5 mg/day, continued up to 4 months) had to taper stepwise and finally discontinue these drugs as long as remission was maintained. Characteristics of patients achieving and not achieving DFR1year were compared and predictors of DFR were identified using logistic regression. Follow up data of 16 months were included to investigate in how many patients DFR1year was sustained for 4 more months. Results 119 patients (32%) achieved DFR1year, while 245 (65%) flared and restarted medication over time. Eleven patients had insufficient data. Of patients in DFR1year, 51 (28%) at baseline fulfilled the 1987 and 2010 classification criteria for RA, 34 (35%) only fulfilled the 2010 criteria and 20 (35%) patients had UA and fulfilled neither criteria (p=0.4). In 77 (65%) DFR1year was sustained up to 16 months. Patients in DFR1year were more often rheumatoid factor (RF) negative than patients not achieving DFR1year, (50% versus 62%, p=0.04). There were no differences in baseline DAS (2.9 (0.9) versus 3.1 (0.8), p=0.12), symptom duration (16 (8-29) versus 17 (9-32), p=0.52) or ACPA positivity (56% versus 61% respectively, p=0.27). Univariable predictors were positive RF (OR 95%CI 0.6 (0.4-0.99)) and high baseline tender joint count (TJC) (OR 95%CI 0.9 (0.9-1.0). Baseline DAS, positive ACPA, age, male sex, being classified as RA according to the 2010 ACR/EULAR criteria or short symptom duration were not predictive for DFR1year. The only independent predictor was RF negativity (OR 95%CI 0.6 (0.4-0.97, adjusted for baseline TJC). Conclusions Of 375 early (rheumatoid) arthritis patients who achieved remission after 4 months of initial combination therapy with methotrexate and prednisone, 32% maintained in remission despite having tapered and discontinued all drugs at 1 year. DFR was sustained up to 16 months in 65% of these. With this treatment strategy, presence of ACPA appears not to preclude drug discontinuation, but patients with positive RF achieved DFR after 1 year somewhat less often than RF negative patients. Disclosure of Interest None Declared

Estudio primario

No clasificado

Un ensayo de dos etapas de tratamiento estrategia en pacientes con artritis temprana dirigido a lograr la remisión: el estudio mejorado.

automatic
Revista Annals of the rheumatic diseases
Año 2014
Enlaces Pubmed DOI
Cargando información sobre las referencias
Evaluar qué tratamiento es la estrategia más eficaz en la inducción de la remisión en la temprana (reumatoide). MÉTODOS: 610 pacientes con artritis reumatoide temprana (RA criterios 2010) o artritis indiferenciada (UA) comenzaron el tratamiento con metotrexato (MTX) y una alta dosis de prednisona cónico. Los pacientes en remisión temprana (Disease Activity Score <1,6 después de 4 meses) prednisona cónica a cero y aquellos con remisión persistente después de 8 meses, cónico y dejaron de MTX. Los pacientes que no están en remisión temprana fueron aleatorizados para recibir MTX más hidroxicloroquina más sulfasalazina más prednisona en dosis bajas (brazo 1) o al MTX más adalimumab (ADA) (brazo 2). Si la remisión estaba presente después de 8 meses afilan ambos brazos al MTX en monoterapia; si no, el brazo 1 cambió a MTX más ADA y el brazo 2 aumentó la dosis de ADA. Las tasas de remisión y los resultados funcionales y radiológicos fueron comparados entre los brazos y entre los pacientes con AR y los que tienen UA. RESULTADOS: 375/610 (61%) pacientes alcanzaron la remisión temprana. Después de 1 año 68% de los que estaban en remisión y 32% en remisión libre de drogas. De los pacientes asignados al azar, 25% en el brazo 1 y el 41% en el brazo 2 alcanzaron la remisión en el año 1 (p <0,01). Los resultados fueron comparables entre los pacientes con AR y los que tienen UA. CONCLUSIONES: MTX inicial y prednisona resultaron en remisión temprana en el 61% de los pacientes con principios (reumatoide). De ellos, el 68% estaban en remisión y el 32% estaban en remisión libre de drogas después de 1 año. En pacientes que no están en remisión temprana, la introducción temprana de ADA se tradujo en más de remisión en el año 1 de tratar primero con la terapia de combinación con fármacos antirreumáticos modificadores de la enfermedad más prednisona.

Estudio primario

No clasificado

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study).

Revista Arthritis research & therapy
Año 2016
Enlaces Pubmed DOI PubMed Central
Cargando información sobre las referencias
BACKGROUND: Early suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients. METHODS: Patients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA. RESULTS: After 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0-0). CONCLUSIONS: After 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed. TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007.

Estudio primario

No clasificado

Clinical and Radiological Outcomes of 5 Years Remission Steered Treatment in Early Rheumatoid and Undifferentiated Arthritis Patients

Conferencia ACR/ARHP Annual Meeting
Año 2016
Enlaces acrabstracts.org
Cargando información sobre las referencias
BACKGROUND/PURPOSE: To assess clinical and radiological outcomes of induction therapy followed by 5 years disease activity score (DAS)-remission steered treatment in early arthritis patients. METHODS: The IMPROVED study enrolled 610 early rheumatoid arthritis (RA, 2010) or undifferentiated arthritis (UA) patients. All started induction therapy methotrexate (MTX) and tapered high dose of prednisone. If DAS-remission (<1.6) was achieved at 4 months prednisone was stopped (early DAS-remission (ER)) and if remission persisted at 8 months MTX was also stopped. Patients not in ER were randomized to MTX+sulfasalazine+hydroxychloroquine+low dose prednisone (arm 1) or MTX+adalimumab (arm 2), 50 patients were not randomized and were treated ‘outside of protocol’ (OP). Every 4 months treatment adjustments aimed at DAS<1.6: DAS<1.6 taper/stop medication and DAS≥1.6 restart/intensify. (Drug-free) DAS-remission percentages were compared between the different diagnosis and treatment strategies. Radiologic damage progression (Sharp-vanderHeijde Score, SHS) from baseline to 5 years was scored by 2 independent readers in chronologic order. RESULTS: Patients in the ER group had better functional ability over time, compared to arms 1 and 2 and the OP group, who between them had similar HAQ scores over time (figure). 295/610 (48%) patients achieved DAS-remission at 5 years: 220/387 (57%) in the ER group, 31/83 (37%) in arm 1, 29/78 (37%) in arm 2 (p=0.768 arm 1 vs arm 2) and 15/50 (30%) in OP (figure). 134/610 (22%) patients achieved DFR (drug-free DAS-remission): 105/387 (27%) in the ER group, 9/83 (11%) in arm 1, 12/78 (15%) in arm 2 (p=0.374 arm 1 vs arm 2) and 8/50 (16%) in OP (figure). DAS-remission percentages were similar in RA and UA patients and autoantibody positive (+) vs negative (‒) patients. More UA patients achieved DFR (33% UA vs 19% RA, p<0.001), and more patients negative for anti-citrullinated protein antibodies (ACPA) (31% ACPAneg vs 15% ACPApos, p<0.001) or rheumatoid factor (RF) (28% RFneg vs 17% RFpos, p<0.001) achieved DFR. Median (IQR) SHS progression was 0.5 (0-3) in 306 completers in the ER group, 0 (0-1) in arm 1 (62 completers), 0 (0-1) in arm 2 (59 completers) (p=0.818 arm 1 vs arm 2) and 0 (0-3) in 31 OP completers. SHS progression ≥5 points had occurred in 40/306 (13%) in the ER group, 9/62 (15%) in arm 1, 7/59 (12%) in arm 2 (p=0.710 arm 1 vs arm 2) and 2/31 (6%). CONCLUSION: Induction therapy followed by 5 years DAS-remission steered treatment resulted in 48% DAS-remission and 22% DFR in early RA and UA patients. More UA patients and more autoantibody negative patients achieved DFR. Radiologic damage progression was well suppressed in the majority of patients.