ORAL Start (NCT01039688)
ID: 59db6cf17db23a15f75a14ec
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Estudio primario

No clasificado

Comparing The Effectiveness And Safety Of 2 Doses Of An Experimental Drug, CP-690,550, To Methotrexate (MTX) In Patients With Rheumatoid Arthritis Who Have Not Previously Received MTX

Autores Pfizer
Registro de estudios clinicaltrials.gov
Año 2010
Enlaces Registro de estudios
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This study is designed to compare the effectiveness of the experimental drug, CP-690,550, to methotrexate in preventing joint damage and improving symptoms of rheumatoid arthritis. This study will also compare the safety of CP-690,550 with methotrexate.

Estudio primario

No clasificado

Radiográfica, comparación clínica y funcional de la monoterapia tofacitinib frente a metotrexato en pacientes con tratamiento previo con metotrexato con artritis reumatoide

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Revista Arthritis & Rheumatism. Abstracts of the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific Meeting Washington, DC November 9-14
Año 2012
Enlaces blackwellpublishing.com Google Scholar
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ANTECEDENTES / OBJETIVO: tofacitinib es un nuevo inhibidor oral de la quinasa Janus siendo investigado como inmunomodulador específico y terapia modificadora de la enfermedad para la AR. Esta fase 3, estudio de 24 meses (inicio ORAL; NCT01039688) eficacia en comparación, incluyendo la inhibición del daño estructural, y la seguridad de tofacitinib versus metotrexato (MTX, 10-20 mg / semana) en-MTX ingenuo pacientes (pts) con AR activa . MÉTODOS: Pts fueron aleatorizados 2: 2: 1 (doble placebo, doble ciego) a: tofacitinib 5 mg dos veces al día (BID); tofacitinib 10 mg dos veces; o MTX 10 mg / sem con incrementos / sem 5 mg cada 4 semanas a 20 mg / sem. Principales criterios de valoración predeterminados (Mo 6) compararon tofacitinib vs MTX para: 1) los cambios medios desde la línea de base (BL) de van der Heijde modificado puntuación total de Sharp (MTSS); 2) respuesta ACR70. Evaluación de la seguridad y la tolerabilidad fue también un objetivo primordial. Los resultados son de los análisis provisionales de 12 mo planificadas. RESULTADOS: En total, 952 pts fueron aleatorizados y tratados con tofacitinib 5 mg BID (N = 371), 10 mg BID (N = 395), y MTX (N = 186). Características de la enfermedad de Demografía y BL con AR, incluyendo puntuaciones radiológicas (MTSS: 20.30, 18.85, y 16.51 para 5 mg dos veces, 10 mg dos veces, y MTX, respectivamente), fueron similares en todos los grupos. Cambios medios de BL en el mTSS y las tasas de ACR70 en Mo 6 fueron estadísticamente superior para ambas dosis de tofacitinib vs MTX (Tabla). Hubo una diferencia estadísticamente significativa en la respuesta ACR70 para ambas dosis de MTX vs tofacitinib por Mo 1 (primera visita post-BL) con el aumento de la eficacia en el tiempo. Puntos finales radiográficos secundarios también fueron significativamente diferentes para tofacitinib vs MTX: pequeños cambios en las puntuaciones de erosión y estrechamiento del espacio articular y una mayor proporción de pts sin progresión de BL (cambio el mTSS <= 0.5) en Mo 6. Otros objetivos secundarios, incluyendo las respuestas ACR20 y ACR50, el cambio medio en DAS28-4 (ESR), DAS28-4 (ESR) <2,6 tasas, y el cambio en HAQ-DI significan, fueron significativamente mejores con tofacitinib vs MTX en todos los puntos de tiempo. La incidencia de acontecimientos adversos (AA) y los EA graves fue similar entre los grupos (Tabla). La mayoría de los acontecimientos adversos fueron leves o moderadas; los acontecimientos adversos más frecuentes en todos los grupos fueron las infecciones. Herpes zoster ocurrió en 2,2%, 2,5% y 1,1% de tofacitinib 5 mg BID, 10 mg BID, y pts MTX, respectivamente; 1 pt tenía tuberculosis ósea (10 mg dos veces) y 1 tenía la infección por citomegalovirus (MTX); 2 pts tofacitinib murieron más tarde en el mismo juicio. La disminución en el recuento de neutrófilos medios y pequeños aumentos en la creatinina sérica media se observaron en todos los grupos. Los aumentos se observaron en LDL y HDL-colesterol niveles medios con tofacitinib. La incidencia de aspartato y alanina aminotransferasa elevaciones> = 3 veces el límite superior de la normalidad fue baja. CONCLUSIÓN: En este estudio de fase 3 tofacitinib monoterapia significativamente inhibió la progresión del daño estructural y la mejora de los signos y síntomas de la AR y el funcionamiento físico vs MTX en pts MTX-naïve. La seguridad de tofacitinib fue similar a la reportada en otros estudios de fase 3 se informó anteriormente.

Estudio primario

No clasificado

Tofacitinib frente a metotrexato en la artritis reumatoide.

automatic
Revista The New England journal of medicine
Año 2014
Enlaces Pubmed DOI
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ANTECEDENTES: El metotrexato es el fármaco antirreumático primera línea usado con mayor frecuencia. Se presentan los resultados de un estudio de fase 3 de la monoterapia con tofacitinib, un inhibidor de la quinasa Janus oral, en comparación con la monoterapia con metotrexato en pacientes con artritis reumatoide que no habían recibido previamente metotrexato o dosis terapéuticas de metotrexato. Métodos: Asignamos aleatoriamente a 958 pacientes para recibir 5 mg o 10 mg de tofacitinib dos veces al día o metotrexato a dosis que se incrementó gradualmente a 20 mg por semana durante 8 semanas; 956 pacientes recibieron un fármaco de estudio. Los criterios de valoración coprimarios en el mes 6 fueron el cambio medio desde el inicio en el van der Heijde modificado puntuación total de Sharp (que va de 0 a 448, con puntuaciones más altas indican mayor daño estructural en las articulaciones) y la proporción de pacientes con un Colegio Americano de Reumatología (ACR) 70 respuesta (reducción ≥70% en el número tanto de articulaciones dolorosas e inflamadas y ≥70% de mejora en tres de los cinco otros criterios: evaluación del dolor del paciente, nivel de discapacidad, C-reactiva nivel de proteína o velocidad de sedimentación globular , la evaluación global de la enfermedad por parte del paciente, y la evaluación global de la enfermedad por el médico). RESULTADOS: Cambios medios en la puntuación total de Sharp modificado desde el inicio hasta el mes 6 fueron significativamente menores en los grupos tofacitinib que en el grupo de metotrexato, pero los cambios fueron modestos en los tres grupos (0,2 puntos en el grupo tofacitinib 5 mg y <0,1 puntos en el grupo de tofacitinib 10 mg, en comparación con el 0,8 puntos en el grupo de metotrexato [P <0,001 para ambas comparaciones]). Entre los pacientes que recibieron tofacitinib, 25,5% en el grupo de 5 mg y 37,7% en el grupo de 10 mg tuvo una respuesta ACR 70 en mes 6, en comparación con 12,0% de los pacientes en el grupo de metotrexato (P <0,001 para ambas comparaciones ). El herpes zóster se desarrolló en 31 de los 770 pacientes que recibieron tofacitinib (4,0%) y en 2 de 186 pacientes que recibieron metotrexato (1,1%). Los casos confirmados de cáncer (incluyendo tres casos de linfoma) desarrollados en 5 pacientes que recibieron tofacitinib y en 1 paciente que recibió metotrexato. Tofacitinib se asoció con aumentos en los niveles de creatinina y de baja densidad y los niveles de colesterol de lipoproteínas de alta densidad. Conclusiones: En los pacientes que no habían recibido previamente metotrexato o dosis terapéuticas de metotrexato, tofacitinib monoterapia fue superior al metotrexato en la reducción de los signos y síntomas de la artritis reumatoide y la inhibición de la progresión del daño estructural en las articulaciones. Los beneficios de tofacitinib necesitan ser considerados en el contexto de los riesgos de eventos adversos. (Financiado por Pfizer;. ORAL número de inicio ClinicalTrials.gov, NCT01039688).

Estudio primario

No clasificado

Relationship between different clinical measurements and patient-reported outcomes: results from a phase 3 study of tofacitinib or methotrexate in methotrexate-naïve patients with rheumatoid arthritis [abstract].

Conferencia Published in: Arthritis Rheum
Año 2014
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Estudio primario

No clasificado

Análisis de las infecciones y por todas las causas de mortalidad en la fase II, fase III, y de extensión a largo plazo los estudios de tofacitinib en pacientes con artritis reumatoide.

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Revista Arthritis & rheumatology (Hoboken, N.J.)
Año 2014
Enlaces Pubmed DOI
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OBJETIVO: Determinar la tasa de infección y mortalidad por cualquier causa a través de tofacitinib fase II, fase III, y la extensión a largo plazo (LTE) estudios en pacientes con moderada a severamente activa de la artritis reumatoide (AR). Se analizaron los datos combinados de los estudios de tofacitinib en pacientes con AR: MÉTODOS. En estos estudios, tofacitinib fue administrado como monoterapia o en combinación con metotrexato u otros fármacos antirreumáticos modificadores de la enfermedad no biológicos. La fecha límite para la inclusión de los datos fue 19 de abril 2012. RESULTADOS: Al otro lado de la fase II, fase III, y los estudios de LTE, 4.789 pacientes recibieron tofacitinib (8.460 pacientes-años de exposición). La tasa global de infección seria era 3,09 eventos por 100 pacientes-año (95% intervalo de confianza [IC 95%] 2,73-3,49), y las tasas se mantuvieron estables en el tiempo. Un modelo de riesgos proporcionales de Cox mostró que la edad, la dosis de corticosteroides, la diabetes, y la dosis tofacitinib estaban relacionados de forma independiente con el riesgo de infección grave. Recuento de linfocitos de <0,5 × 10 (3) / mm (3) fueron rara pero se asocia con un mayor riesgo de infección tratada y / o grave. En general, todas las causas de mortalidad fueron las tasas de 0,30 eventos por 100 pacientes-año (IC del 95%: 0,20 hasta 0,44). CONCLUSIÓN: El riesgo general de infección (incluyendo infección grave) y mortalidad en los pacientes con AR tratados con tofacitinib parecen ser similares a los observados en los pacientes con AR tratados con agentes biológicos. Las tasas de infección grave se mantuvieron estables en el tiempo.

Estudio primario

No clasificado

Relationship between different clinical measurements and patient-reported outcomes: Results from a phase 3 study of tofacitinib or methotrexate in methotrexate-naïve patients with rheumatoid arthritis

Conferencia Published in: Annals of the Rheumatic diseases
Año 2015
Enlaces DOI www.cochranelibrary.com
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Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives: Here we compare the relationship between clinical measures and patient-reported outcomes (PROs) in patients (pts) with RA treated with tofacitinib or methotrexate (MTX). Methods: MTX-naïve pts with RA from a double-blind, parallel group, Phase 3 trial (ORAL Start; NCT01039688) were randomised (2:2:1) and treated with tofacitinib 5 mg twice daily (BID) monotherapy (N=373), tofacitinib 10 mg BID monotherapy (N=397) or MTX titrated from 10 to 20 mg/week (N=186). Clinical measures included: the proportion of pts achieving ACR50 and ACR70 responses, the proportion achieving low disease activity (LDA) measured by Clinical Disease Activity Index (CDAI LDA, CDAI≤10) and Simplified Disease Activity Index (SDAI LDA, SDAI≤11), and the proportion achieving remission (REM) measured by CDAI REM (CDAI≤2.8) and SDAI REM (SDAI≤3.3). PROs included: proportion of pts achieving improvements in physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI, to normative values <0.5). Results: At Month 6, a greater proportion of pts achieved ACR responses, LDA and REM with tofacitinib 5 mg or 10 mg BID than with MTX (Table 1). Most pts who achieved LDA and REM by one measure also achieved LDA and REM by other measures (Table 1); however, discordance was observed between different measures of LDA and REM, and appeared greater with MTX vs either tofacitinib dose (Table 1). As expected there was a high degree of concordance between Overall, pts achieving LDA or ACR50 showed less improvement from baseline in patient-reported pain, and patient global assessment of disease compared with tender joints, swollen joints, physician global assessment of disease and HAQ-DI: pts receiving MTX showed an overall lower improvement in these PROs compared with tofacitinib 5 mg or 10 mg BID. In general, better improvements and consistency in PROs were observed in ACR50 responders compared with measures of LDA. Pts achieving ACR70, CDAI REM and SDAI REM showed similar improvements across PROs and similarly between MTX and tofacitinib. Conclusions: A higher proportion of MTX-naïve pts receiving tofacitinib 5 or 10 mg BID achieved a clinical response compared with pts receiving MTX. While most pts achieve similar responses across different clinical measures, many may achieve a response in one measure but not the other. Variability of responses with clinical measures should be considered when setting treat-to-target goals in pts with RA.

Estudio primario

No clasificado

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme.

Revista Annals of the rheumatic diseases
Año 2016
Enlaces Pubmed DOI PubMed Central
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OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme. METHODS: Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies. RESULTS: Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA. CONCLUSIONS: The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure.

Estudio primario

No clasificado

Lack of early change in disease activity score predicts the likelihood of achieving low disease activity at month 6: Tofacitinib monotherapy versus methotrexate in methotrexate-naïve patients with rheumatoid arthritis

Revista Annals of the Rheumatic Diseases
Año 2016
Enlaces DOI www.cochranelibrary.com
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Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Treatment guidelines recommend targeting remission or low disease activity (LDA), herein defined as Disease Activity Scores ≤3.2 based on 28 joint counts (DAS28≤3.2) and adjusting therapy after 3-6 months1 (Mos). Predicting the likelihood of clinical response may help inform early treatment decisions. Objectives: To understand the relationship between timing and magnitude of early changes in DAS28, erythrocyte sedimentation rate (DAS28-4[ESR]) and the likelihood of achieving LDA at Mo 6 in RA patients (pts) naïve to methotrexate (MTX). Methods: In a Phase 3 study (ORAL Start; NCT01039688), MTX-naïve RA pts were randomised 2:2:1 to the following monotherapies: tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or MTX. Conditional probability of pts achieving LDA at Mo 6 were calculated, given failure to achieve DAS28-4(ESR) improvement from baseline (range ≥0.3 to 1.8) at Mo 1 or 3. One-year data with non-responder imputation for missing values was used. Results: 948 pts received treatment; tofacitinib 5 mg BID (n=370), tofacitinib 10 mg BID (n=394) or MTX (n=184); results previously reported.2 In this post-hoc analysis, of those patients who failed to achieve DAS28-4(ESR) improvement from baseline ≥1.2 at Mo 3, 6.8% for tofacitinib 5 mg BID, 11.3% for tofacitinib 10 mg BID and 6.2% for MTX achieved LDA at Mo 6 (Table). A minority of pts (74/353 [20.9%]) receiving tofacitinib 5 mg BID failed to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3, while a greater proportion failed for MTX (65/171 [38.0%]). Failure to achieve DAS28-4(ESR) improvement from baseline at Mo 3 (range ≥0.30-1.8) for tofacitinib 5 mg BID and MTX was associated with a low probability (≤10%) of achieving LDA at Mo 6. For tofacitinib 5 mg BID, failure to achieve lower thresholds of DAS28-4(ESR) improvement (range ≥0.3 to 0.9) at Mo 1 was associated with lower probability of LDA at Mo 6 than higher DAS28-4(ESR) thresholds (≥1.2-1.8) (Table). Conclusions: Failure to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3 was associated with a low probability of achieving LDA at Mo 6 (≤6.8%) for tofacitinib 5 mg BID and MTX. For the minority of MTX-naïve RA pts treated with tofacitinib 5 mg BID or MTX who failed to achieve a minimal clinical response (DAS28-4[ESR] improvement ≥1.2) by Mo 3, another treatment option can be considered at Mo 3, as there is a low probability of reaching LDA at Mo 6. (Table Presented).

Estudio primario

No clasificado

Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial.

Revista RMD open
Año 2016
Enlaces Pubmed DOI PubMed Central
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OBJECTIVES: To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. METHODS: In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36]). RESULTS: PROs improved following tofacitinib and MTX treatment: benefits were sustained over 24 months. Patients receiving tofacitinib reported earlier responses which were significantly different between each tofacitinib dose and MTX at month 3 through month 24. At month 6 (primary end point), significant improvements versus MTX were observed in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 5/8 domain scores and FACIT-F with tofacitinib 5 mg two times per day; all PROs, except SF-36 Mental Component Summary Score and Medical Outcomes Survey-Sleep, with tofacitinib 10 mg two times per day. At month 6, the proportion of patients reporting improvements ≥minimum clinically important difference were significant versus MTX with tofacitinib 5 mg two times per day in PtGA and 3/8 SF-36 domains; and with tofacitinib 10 mg two times per day in PtGA, pain, HAQ-DI, SF-36 PCS, 4/8 domains and FACIT-F. CONCLUSIONS: Patients with rheumatoid arthritis receiving tofacitinib 5 and 10 mg two times per day monotherapy versus MTX reported statistically significant and clinically meaningful improvements in multiple PROs over 24 months; onset of benefit with tofacitinib treatment occurred earlier. TRIAL REGISTRATION NUMBER: NCT01039688.

Estudio primario

No clasificado

Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis.

Revista Annals of the rheumatic diseases
Año 2016
Enlaces Pubmed DOI PubMed Central www.cochranelibrary.com
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OBJECTIVES: To evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: Phase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05). RESULTS: We identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)). CONCLUSIONS: Within the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.

Estudio primario

No clasificado

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

Revista RMD open
Año 2016
Enlaces Pubmed DOI PubMed Central
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INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. METHODS: MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. RESULTS: Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. CONCLUSIONS: Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. TRIAL REGISTRATION NUMBER: NCT01039688; Results.

Estudio primario

No clasificado

Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies.

Revista Rheumatology (Oxford, England)
Año 2017
Enlaces Pubmed DOI www.cochranelibrary.com
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OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. METHODS: Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration. Disease activity markers included CRP and ESR. Fatigue and vitality were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Short Form Health Survey-36 vitality domain scores. RESULTS: In phase 3 studies, mean neutrophil and lymphocyte counts decreased and mean haemoglobin levels increased in all tofacitinib treatment groups. Haemoglobin levels and neutrophil counts stabilized in the LTE studies, while lymphocyte count decreases stabilized at approximately month 48. Increased haemoglobin was associated with decreased ESR and CRP levels. Clinically meaningful reductions in haemoglobin levels (⩾3 g/dl from baseline or haemoglobin ⩽7 g/dl) occurred in <1.0% of patients in all treatment groups. FACIT-F and Short Form Health Survey-36 vitality scores were weakly correlated with haemoglobin levels. CONCLUSION: Small changes in haematological parameters were seen with tofacitinib treatment, which stabilized over time in the LTE studies. Changes in haemoglobin levels, although associated with changes in ESR and CRP, were not associated with fatigue or vitality.

Estudio primario

No clasificado

Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6.

Revista Arthritis care & research
Año 2019
Enlaces Pubmed DOI PubMed Central www.cochranelibrary.com
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OBJECTIVE: Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post hoc analysis explored the relationship between early disease activity changes and the achievement of low disease activity (LDA) and remission targets with tofacitinib. METHODS: Data were from 2 randomized, double-blind, phase III studies. In the ORAL Start trial, methotrexate (MTX)-naive patients received tofacitinib 5 or 10 mg twice daily, or MTX, for 24 months. In the placebo-controlled ORAL Standard trial, MTX inadequate responder patients received tofacitinib 5 or 10 mg twice daily or adalimumab 40 mg every 2 weeks, with MTX, for 12 months. Probabilities of achieving LDA (using a Clinical Disease Activity Index [CDAI] score ≤10 or the 4-component Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6 or DAS28-ESR ≥1.2) at month 1 or 3. RESULTS: In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to show improvement in the CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering improvements at month 1 or DAS28-ESR thresholds. CONCLUSION: In patients with an inadequate response to MTX, lack of response to tofacitinib after 1 or 3 months predicted a low probability of achieving LDA at month 6. Lack of an early response may be considered when deciding whether to continue treatment with tofacitinib.