The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid ...arthritis (RA) on low-dose methotrexate (MTX) or without MTX.
A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents.
Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model.
Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.
Particle detachment from an obliquely oscillating plate was studied experimentally and theoretically. The plate was placed in a horizontal position, and vibrations were applied in the horizontal and ...vertical directions by piezoelectric vibrators. The frequency of vibration was constant at 280Hz. The amplitude of vibration increased with time and approached a constant value in each experiment. The movement of micrometer-sized spherical particles was analyzed using images captured by a high-speed microscope camera, which showed that the particles rolled on the plate before detaching from the surface, and that the rolling significantly reduced the adhesive force between the particles and surface. Furthermore, the removal efficiency, defined by the number ratio of detached particles to total particles, was analyzed as a function of the horizontal and vertical vibration accelerations. It was found that the removal efficiency was significantly affected by the horizontal vibration acceleration. These experimental results can be explained by the force and moment balance model.
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•We experimentally study the particle detachment from an obliquely oscillating plate.•We analyze the motion of micro-sized spherical particles by microscopic observation.•The particles roll on the plate before detaching from the surface.•The roll significantly reduces the adhesive force between the particles and surface.•The particle movement can be explained by the force and moment balance model.
•Of RA patients with sustained low disease activity receiving tocilizumab plus methotrexate, 69.4% maintained low disease activity at 52weeks after methotrexate discontinuation.•Male patients and ...those receiving tocilizumab at an extended dosing interval were at high risk of disease flare after discontinuation of concomitant methotrexate.•Methotrexate discontinuation reduced the prevalence of gastroesophageal reflux disease in RA patients.
To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy.
Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index CDAI≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models.
Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval CI) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6–81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio OR: 18.00, 95% CI: 2.80–115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72–83.80) were independent predictors of disease flare.
Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate.
jRCTs041180071, UMIN000021247.
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•We experimentally study the particle saltation on an obliquely oscillating plate.•We analyze the motion of different-sized particles by microscopic observation.•The particles are ...transported by the repeated forward and backward bounces.•The ratio of the backward to the total bounces depends on the particle diameter.•The particle motion can be explained by a theoretical probability model.
This paper presents a microscopic analysis of the saltation of particles on an obliquely oscillating plate driven by sine waves with an amplitude on the order of tens of micrometers and a frequency on the order of hundreds of hertz. To examine the effect of the diameter of a particle on its motion, the trajectories and velocities of different-sized particles, from 0.5 to 500μm in mass median diameter, are analyzed using images captured by a high-speed microscope camera. The results show that larger particles bounce higher, whereas smaller particles easily agglomerate and bounce only slightly, owing to the low restitution caused by their loosely packed structure. In addition, larger particles bounce forward and backward repeatedly, while the agglomerated particles always bounce forward, and consequently have the highest transport velocity among these particles. The particle motion and the transport velocity can be explained by a theoretical probability model.
We demonstrate that a vibration-induced air inflow can cause vigorous bubbling in a bed of fine particles and report the mechanism by which this phenomenon occurs. When convective flow occurs in a ...powder bed as a result of vibrations, the upper powder layer with a high void ratio moves downward and is compressed. This process forces the air in the powder layer out, which leads to the formation of bubbles that rise and eventually burst at the top surface of the powder bed. A negative pressure is created below the rising bubbles. A narrow opening at the bottom allows the outside air to flow into the powder bed, which produces a vigorously bubbling fluidized bed that does not require the use of an external air supply system.
The saltation of fine particles on an obliquely oscillating plate was simulated using a mass-point model that considered the gravity, fluid resistance, restitution, and friction. To examine the ...effects of the restitution and fluid resistance on the horizontal transport velocity, the two-dimensional movements of three particles with different coefficients of restitution and diameters were calculated. The results showed that a particle with a higher restitution and smaller diameter had a smaller transport velocity. This can be explained as follows. A particle with a higher restitution bounces forward and backward repeatedly, whereas a particle with a lower restitution only bounces forward, because the higher bounce height increases the impulse exerted on the particle during a collision, which induces a drastic change in the horizontal velocity from the collision. The horizontal velocity of a smaller particle is decreased by the drag force during its flight between successive collisions.
Étudier les facteurs prédictifs de poussée de polyarthrite rhumatoïde (PR) après arrêt du méthotrexate chez des patients japonais présentant une faible activité stable de la maladie sous traitement ...combiné de tocilizumab (TCZ) et méthotrexate (MTX).
Cette étude prospective multicentrique en ouvert non contrôlée porte sur des patients japonais atteints de PR présentant une faible activité de la maladie (indice CDAI Clinical Disease Activity Index ≤ 10) depuis ≥ 12 semaines sous traitement combiné de TCZ et MTX. Le MTX a été arrêté après 12 semaines d’administration toutes les deux semaines tandis que le TCZ était maintenu. Une poussée de la maladie a été définie comme soit un score CDAI > 10, soit l’administration d’un traitement de secours pour quelque cause que ce soit, même avec un CDAI ≤ 10. L’influence des caractéristiques à l’inclusion sur les poussées de la maladie à la semaine 64 (52 semaines après l’arrêt du MTX) a été évaluée par des modèles de régression logistique.
Des analyses d’efficacité ont été effectuées chez 49 patients, dont 15 avaient présenté une poussée de la maladie à la semaine 64. La proportion (intervalle de confiance IC à 95 %) de patients ayant une faible activité de la maladie sans poussée à la semaine 64 était de 69,4 % (54,6–81,8 %). L’intervalle d’administration du TCZ était plus long que celui indiqué sur l’étiquette au Japon (c.-à-d. administration par intraveineuse toutes les quatre semaines ou sous-cutanée toutes les deux semaines) chez 27 % des patients présentant une poussée et 6 % des patients sans poussée. Selon l’analyse multivariée, le sexe masculin (odds ratio OR 18,00, IC 95 % 2,80–115,56) et l’intervalle d’administration étendu du TCZ (OR 12,00, IC 95 % 1,72–83,80) étaient des facteurs prédictifs indépendants de poussée de la maladie.
Les patients de sexe masculin et ceux recevant du TCZ selon un intervalle étendu présentent un risque élevé de poussée de la maladie après l’arrêt du MTX concomitant.
jRCTs041180071, UMIN000021247.
•We numerically study the particle saltation on an obliquely oscillating plate.•Particle saltation is simulated using a mass-point model.•The calculated trajectories are in good agreement with ...experimental results.•The phase angle of the oscillation and the impulse during collision are analyzed.
Particle saltation on an obliquely oscillating plate is simulated using a mass-point model that considers gravity, fluid resistance, restitution, and friction. The calculated results are in good agreement with results obtained experimentally for particles with different diameters and restitutions. A large particle with high restitution bounces forward and backward repeatedly, whereas a particle with low restitution only bounces forward and consequently has a high transport velocity. The mechanism for the difference in the motion of the particles can be explained by taking into account the phase angle of the oscillating plate and the impulse during particle collision.
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