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OBJECTIVES: We investigated whether our in-house software equipped with partial image phase-only correlation (PIPOC) can detect subtle radiographic joint space narrowing (JSN) progression at six months and predict JSN progression in rheumatoid arthritis (RA) patients receiving Tocilizumab. METHODS: The study included 39 RA patients who were treated with Tocilizumab. Radiological progression of the metacarpophalangeal and the proximal interphalangeal joints was evaluated according to the Genant-modified Sharp score (GSS) at 0, 6, and 12 months. Automatic measurements were performed with the software. We validated the software in terms of accuracy in detecting the JSN progression. RESULTS: The success rate of the software for joint space width (JSW) measurement was 96.8% (449/464). The 0-12-month JSW change by the software was significantly greater in joints with the 0-6-month PIPOC (+) group than the 0-6-month PIPOC (-) group (p < 0.001). The 0-12-month JSW change by the software was 0-12-month GSS (+) than with 0-12-month GSS (-) (p = 0.02). Here, "(+)" indicates the JSN progression during the follow-up period. Meanwhile, "(-)" indicates no JSN progression during the follow-up period. Linear regression tests showed significant correlations between the 0-6-month and the 0-12-month PIPOC in the left 2nd and 3rd MCP joints (R2 = 0.554 and 0.420, respectively). CONCLUSIONS: Our in-house software equipped with PIPOC could predict subsequent JSN progression with only short-term observations.
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OBJECTIVES: To assess the usefulness and onset of nocebo effects after switching from the original etanercept (ETN) to a biosimilar (BS) in routine clinical practice at rheumatology clinics in Japan (13 sites). METHODS: A total of 165 patients (87.0% women, age = 57.88 ± 15.07 years, and disease duration = 10.32 ± 7.71 years), whose low disease activity was maintained with the original ETN for ≥12 weeks, and who agreed to switch treatment to its BS, were included. The end-points were disease activity score 28 (DAS28)-C-reactive protein and DAS28-erythrocyte sedimentation rate. RESULTS: No significant difference was observed between the changes in DAS28-C-reactive protein and DAS28-erythrocyte sedimentation rate >12 weeks before switching and >12 weeks after switching (P = 0.132 and 0.334, respectively). The treatment continuation rate during the 52 weeks after switching to BS was 97.3%. During this period, BS was discontinued in only four patients, and no nocebo effects were suspected in these four patients. CONCLUSION: Switching from ETN to BS was effective even in routine clinical practice at rheumatology clinics in Japan, and no nocebo effects were observed. Sufficient explanations to patients by rheumatologists and the additional payment for drug costs between patients at hospital visits effectively improved the continuation rate without any nocebo effect.
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Antirreumáticos , Artritis Reumatoide , Biosimilares Farmacéuticos , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Etanercept/uso terapéutico , Antirreumáticos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Efecto Nocebo , Japón , Proteína C-Reactiva , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
OBJECTIVE: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. METHODS: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. RESULTS: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. CONCLUSION: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.
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Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/tratamiento farmacológico , Ácido Risedrónico/uso terapéutico , Anciano , Artritis Reumatoide/tratamiento farmacológico , Densidad Ósea , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Método Doble Ciego , Femenino , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Vértebras Lumbares/patología , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Ácido Risedrónico/administración & dosificación , Ácido Risedrónico/efectos adversosRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase in a 2-part, phase II trial (RAjuvenate; ClinicalTrials.gov: NCT02628028) in adults with active rheumatoid arthritis (RA). METHODS: In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5, 10, or 30 mg or placebo once daily for 4 weeks to assess safety and tolerability. No safety signals precluded moving to Part B, where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5 mg (n = 63), 10 mg (n = 62), or 30 mg (n = 63), or placebo (n = 62) once daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary and secondary endpoints. Nonresponder imputation was used for missing data. RESULTS: After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. One hundred and eighty-nine (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (P > 0.05 for all comparisons). Five serious adverse events occurred (n = 2, placebo; n = 3, 30 mg); there was 1 death due to a fall. CONCLUSION: While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA.
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Antirreumáticos , Artritis Reumatoide , Adulto , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Método Doble Ciego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In rheumatoid arthritis (RA), the radiographic progression of joint space narrowing (JSN) is evaluated using visual assessments. However, those methods are complicated and time-consuming. We developed an automatic system that can detect joint locations and compute the joint space difference index (JSDI), which was defined as the chronological change in JSN between two radiographs. The purpose of this study was to establish the validity of the software that automatically evaluates the temporal change of JSN. This study consisted of 39 patients with RA. All patients were treated with tocilizumab and underwent hand radiography (left and right hand separately) at 0, 6, and 12 months. The JSN was evaluated using mTSS (modified Total Sharp Score) by one musculoskeletal radiologist as well as our automatic system. Software measurement showed that JSDI between 0 and 12 months was significantly higher than that between 0 and 6 months (p < 0.01). While, there was no significant difference in mTSS between 0, 6, and 12 months. The group with higher disease activity at 0 months had significantly higher JSDI between 0 and 6 months than that with lower disease activity (p = 0.02). The automatic software can evaluate JSN progression of RA patients in the finger joint on X-ray.
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Artritis Reumatoide , Articulaciones de los Dedos , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Articulaciones de los Dedos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Programas InformáticosRESUMEN
BACKGROUND: Although rheumatoid arthritis (RA) causes destruction of articular cartilage, early treatment significantly improves symptoms and delays progression. It is important to detect subtle damage for an early diagnosis. Recent software programs are comparable with the conventional human scoring method regarding detectability of the radiographic progression of RA. Thus, automatic and accurate selection of relevant images (e.g. hand images) among radiographic images of various body parts is necessary for serial analysis on a large scale. OBJECTIVE: In this study we examined whether deep learning can select target images from a large number of stored images retrieved from a picture archiving and communication system (PACS) including miscellaneous body parts of patients. METHODS: We selected 1,047 X-ray images including various body parts and divided them into two groups: 841 images for training and 206 images for testing. The training images were augmented and used to train a convolutional neural network (CNN) consisting of 4 convolution layers, 2 pooling layers and 2 fully connected layers. After training, we created software to classify the test images and examined the accuracy. RESULTS: The image extraction accuracy was 0.952 and 0.979 for unilateral hand and both hands, respectively. In addition, all 206 test images were perfectly classified into unilateral hand, both hands, and the others. CONCLUSIONS: Deep learning showed promise to enable efficiently automatic selection of target X-ray images of RA patients.
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Aprendizaje Profundo , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiografía/métodos , Artritis Reumatoide/diagnóstico por imagen , Mano/diagnóstico por imagen , HumanosRESUMEN
AIMS: We compared the incidence of adverse events between single and divided-dose regimens of methotrexate (MTX) by using a multicenter randomized controlled trial. METHODS: Eighty-nine patients with insufficient control on MTX 8 mg/wk were randomly assigned into single-dose (39 patients) or triple dose (39 patients) groups. The MTX dose for all patients was gradually increased to 16 mg/wk. The primary endpoint was the occurrence of liver dysfunction during the observation period (20 weeks). RESULTS: There were no differences in baseline data and MTX dose at Week 20 between groups. There was no significant difference in the incidence of liver dysfunction between groups (single dose, 3 [7.7%] patients vs. triple dose, 5 [13.2%] patients; P = .455). The incidence of adverse event increased in triple dose (single dose, 12 [30.8%] patients vs. triple dose, 20 [51.3%]), but the difference was not significant (P = .066). There was no significant difference in disease activity between groups, although MTX-triglutamate (PG3), MTX-PG4, and MTX-PG5 were significantly higher in the single dose group. CONCLUSIONS: Weekly split dosing reduced the polyglutamation of MTX. There was no significant difference in efficacy and safety between the 2 groups.
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Artritis Reumatoide/tratamiento farmacológico , Eritrocitos/metabolismo , Metotrexato/administración & dosificación , Ácido Poliglutámico/sangre , Administración Oral , Antirreumáticos/administración & dosificación , Artritis Reumatoide/sangre , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eritrocitos/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Poliglutámico/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Causes of weight change after tocilizumab treatment are unclear. We aimed to investigate the effects of tocilizumab treatment on body weight and serum adipokine levels in patients with rheumatoid arthritis (RA). METHODS: In this retrospective cohort study, we evaluated weight changes in patients with RA who received methotrexate (Cohort I) or tocilizumab with methotrexate (Cohorts II and III) for 24 weeks. Adipokine concentrations at baseline and 24 weeks were analyzed in Cohorts I and III. Cohorts I and II received tocilizumab therapy for an additional 48 weeks, during which weight changes were monitored (24-72 weeks). RESULTS: No significant weight change occurred after 24 weeks of methotrexate treatment (mean difference, -0.2 kg; P = 0.630), but was observed after 24 weeks of tocilizumab treatment (mean difference, +0.9 kg; P = 0.010). Weight changed regardless of the treatment response in both treatment groups. The leptin-adiponectin ratio (P = 0.015) and levels of adiponectin (P < 0.001), leptin (P < 0.001), and resistin (P = 0.003) increased significantly after 24 weeks of tocilizumab, but not methotrexate treatment. After 24, 48 and 72 weeks of tocilizumab treatment in Cohort II, mean (95% confidence interval [CI]) weight changes from baseline were +0.7 (0.0-1.4), +1.2 (0.4-2.0) and +1.1 (0.2-2.0) kg, respectively, and mean (95% CI) percent weight changes from baseline were +1.3% (0.1%-2.6%), +2.2% (0.7%-3.6%), and +2.0% (0.4%-3.7%) at 24, 48, and 72 weeks, respectively. CONCLUSION: Weight and the leptin-adiponectin ratio increased after tocilizumab treatment. Given that cardiovascular (CV) risk factors may deteriorate in patients with RA who receive tocilizumab, further studies are required to determine the effects of weight gain on CV outcomes in these patients.
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Adiponectina/sangre , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Leptina/sangre , Resistina/sangre , Peso Corporal/efectos de los fármacos , Quimioterapia Combinada , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Receptores de Interleucina-6/antagonistas & inhibidores , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for treatment of RA in Japan in 1999 at the recommended dose of 6-8 mg/week; it was approved as first-line drug with the maximum dose of 16 mg/week in February 2011. However, more than half of Japanese patients with RA are unable to tolerate a dose of 16 mg/week of MTX. Moreover, some serious adverse events during the treatment with MTX, such as pneumocystis pneumonia (PCP) and lymphoproliferative disorders (LPD) have been observed much more frequently in Japan than in other countries. Therefore, this article, an abridged English translation summarizing the 2016 update of the Japan College of Rheumatology (JCR) guideline for the use of MTX in Japanese patients with RA, is not intended to be valid for global use; however, it is helpful for the Japanese community of rheumatology and its understanding might be useful to the global community of rheumatology.
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Artritis Reumatoide/tratamiento farmacológico , Trastornos Linfoproliferativos , Metotrexato , Neumonía por Pneumocystis , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Japón/epidemiología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/prevención & control , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/etiología , Neumonía por Pneumocystis/prevención & control , Ajuste de Riesgo/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. METHODS: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. RESULTS: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. CONCLUSIONS: Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.
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OBJECTIVES: Combination treatment with methotrexate, salazosulfapyridine and bucillamine as an alternative to treatment with TNF-inhibiting biologics in rheumatoid arthritis was investigated. METHODS: Twenty-six facilities allied with the Japan Association of Rheumatologists in Private Practice participated in this study. One hundred and twelve patients enrolled in this study, all of whom were within 3 years of diagnosis with rheumatoid arthritis for whom treatment with one DMARD or a combination of two DMARDs had failed (DAS28 > 3.2). Patients chose their own treatment. The triple DMARDs combination group was comprised of 72 patients; the TNF-inhibiting biologics treatment group was comprised of 40 patients. RESULTS: DAS28 scores for the triple DMARDs combination group and the TNF-inhibiting biologics treatment groups were 4.84 ± 0.96 and 5.23 ± 1.26, and there was no significant difference between the two groups. From the 6th month, average disease activities of both groups were reduced, and there was no difference between the two groups at 12 months (DAS28, 3.39 ± 1.43 and 3.05 ± 1.43, p = 0.39). Furthermore, there was no significant difference in the degree of bone destruction between the two groups at 12 months. CONCLUSIONS: The triple DMARD combination therapy provided a new treatment option for those patients for whom treatment with biologics is difficult.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Cisteína/análogos & derivados , Metotrexato/uso terapéutico , Sulfasalazina/uso terapéutico , Adulto , Anciano , Productos Biológicos/uso terapéutico , Cisteína/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Artritis Reumatoide/diagnóstico , Articulaciones de los Dedos/patología , Membrana Sinovial/patología , Adulto , Artritis Reumatoide/diagnóstico por imagen , Capilares/diagnóstico por imagen , Capilares/patología , Femenino , Articulaciones de los Dedos/irrigación sanguínea , Articulaciones de los Dedos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Fantasmas de Imagen , Proyectos Piloto , Reproducibilidad de los Resultados , Membrana Sinovial/irrigación sanguínea , Membrana Sinovial/diagnóstico por imagen , Ultrasonografía Doppler/instrumentación , Ultrasonografía Doppler/métodosRESUMEN
We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Receptores de Interleucina-6/inmunología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Reumatoide/sangre , Sedimentación Sanguínea , Ensayos Clínicos Fase III como Asunto , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Retratamiento , Índice de Severidad de la Enfermedad , Sinovitis/diagnóstico por imagen , Sinovitis/etiología , Resultado del Tratamiento , UltrasonografíaRESUMEN
In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple institutes who fulfilled the American Rheumatism Association 1987 revised criteria for the classification of RA, and followed the clinical results of disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the aim of developing therapeutic guidelines using the disease activity score 28 (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC), one of the most widely used DMARDs in Japan. Eighty-one patients with early RA who had not previously been treated with DMARDs were suitable for BUC therapy as first-choice treatment. After 24 months of treatment, at least moderate improvement was seen in 87.5% of patients using the DAS28 erythrocyte sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of DAS28 (ESR) <2.6. The 24-month BUC continuation rate was 60.5% (49/81, monotherapy + combination therapy), of which 59.2% (29/49) were on BUC monotherapy. From the efficacy and safety viewpoints alike, BUC was useful as first-choice treatment for early RA.
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Antiinflamatorios no Esteroideos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Cisteína/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Niño , Cisteína/administración & dosificación , Cisteína/efectos adversos , Diagnóstico Precoz , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Inducción de Remisión , Resultado del Tratamiento , Adulto JovenRESUMEN
To compare magnetic resonance imaging (MRI) and ultrasonography (US) in the detection of joint inflammation of rheumatoid arthritis (RA), 6 patients with RA were examined by US and low-field 0.3-T nonenhanced dedicated extremity MRI (compacTscan). All patients were females, with mean age of 50.2 years, mean disease duration of 13.5 years, and mean disease activity score (DAS)28-CRP of 1.78. Each patient was treated with either infliximab, etanercept, adalimumab, or tocilizumab. Intercarpal joints, radioulnar joints, second through fifth proximal interphalangeal (PIP) joints, and first through fifth metacarpophalangeal (MCP) joints (a total of 132 joints, 22 joints in each patient) were assessed by MRI for presence of joint inflammation. A total of 156 joints (24 first interphalangeal and radiocarpal joints plus the above 132 joints), were assessed by grayscale US (GS-US) and power Doppler US (PD-US) for presence of joint inflammation by two trained ultrasonographers. We assessed correlations between joint inflammations on MRI and GS-US/PD-US, and also interobserver correlation between the two ultrasonographers by calculating intraclass correlation coefficients (ICC). Synovial hypertrophy and/or synovial fluid was detected in 74/156 joints on GS-US, and synovitis was detected in 10/156 joints on PD-US and in 38/132 joints on MRI. Using PD-US as a reference, sensitivity of MRI in detection of synovitis was 80%. Using MRI as a reference, sensitivity of PD-US was 21%. Specificity of PD-US was higher than that of MRI. Overall agreement between GS-US and MRI and between PD-US and MRI was 0.56 and 0.76, respectively, suggesting that results of PD-US are close to those of MRI. ICC was 0.545 for GS-US and 0.807 for PD-US, suggesting specificity of PD-US in detecting joint inflammation. Our results show that findings of PD-US correlated with those of MRI. Low-field MRI and PD-US are useful tools for assessment of patients with RA.
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Artritis Reumatoide/diagnóstico , Articulaciones de la Mano/patología , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodos , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Estado de Salud , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
PURPOSE: To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. METHODS AND MATERIALS: Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. RESULTS: Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. CONCLUSION: PDUS reflected infliximab's effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.
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Anticuerpos Monoclonales/administración & dosificación , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Interpretación de Imagen Asistida por Computador/métodos , Sinovitis/diagnóstico por imagen , Sinovitis/tratamiento farmacológico , Ultrasonografía Doppler/métodos , Adulto , Anciano , Algoritmos , Antirreumáticos/administración & dosificación , Femenino , Articulaciones de los Dedos/diagnóstico por imagen , Articulaciones de los Dedos/efectos de los fármacos , Estudios de Seguimiento , Humanos , Aumento de la Imagen/métodos , Infliximab , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Ultrasonografía Doppler/efectos de los fármacosRESUMEN
OBJECTIVE: To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA. METHODS: The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it. RESULTS: Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P = 0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of <60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 +/- 9.4 vs 10.1 +/- 8.1 mg/dl, P = 0.03) and a low albumin level (2.7 +/- 0.6 vs 3.3 +/- 0.5 g/dl, P = 0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 +/- 394 vs 1203 +/- 399/microl, P = 0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered. CONCLUSIONS: Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Isoxazoles/efectos adversos , Lesión Pulmonar/inducido químicamente , Anciano , Compuestos de Anilina/sangre , Antirreumáticos/uso terapéutico , Proteína C-Reactiva/análisis , Crotonatos , Femenino , Humanos , Hidroxibutiratos/sangre , Hipoxia/complicaciones , Isoxazoles/uso terapéutico , Japón/epidemiología , Leflunamida , Enfermedades Pulmonares Intersticiales/complicaciones , Lesión Pulmonar/sangre , Lesión Pulmonar/mortalidad , Lesión Pulmonar/patología , Masculino , Persona de Mediana Edad , Nitrilos , Vigilancia de Productos Comercializados , Pronóstico , Respiración Artificial , Factores de Riesgo , Albúmina Sérica/metabolismo , ToluidinasRESUMEN
OBJECTIVES: The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan. METHODS: We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan. Multivariable logistic analysis was performed to identify the risk factors for newly developed and/or exacerbation of ILD. RESULTS: Sixty-one (1.2%) of 5054 RA patients who received LEF were reported to have development and/or exacerbation of ILD as an adverse drug reaction to LEF, judged by the attending physicians. Multivariable logistic regression analysis identified pre-existing ILD [odds ratio (OR) 8.17; 95% CI 4.63, 14.4], cigarette smoking (3.12; 95% CI 1.73, 5.60), a low body weight (<40 kg vs >50 kg) (2.91; 95% CI 1.15, 7.37) and the use of a loading dose (3.97; 95% CI 1.22, 12.9) as independent risk factors for LEF-induced ILD. CONCLUSIONS: Pre-existing ILD was the most important risk factor for LEF-induced ILD. We suggest that LEF should not be prescribed for RA patients complicated with ILD.
Asunto(s)
Antirreumáticos/efectos adversos , Isoxazoles/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Peso Corporal , Femenino , Humanos , Isoxazoles/uso terapéutico , Japón/epidemiología , Leflunamida , Enfermedades Pulmonares Intersticiales/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Vigilancia de Productos Comercializados , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiologíaRESUMEN
Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n=9) and without (n=13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory.