Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid arthritis: a prospective cohort study in Japan.

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Complete renal response at 12 months after induction therapy is associated with renal relapse-free rate in lupus nephritis: a single-center, retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.

Diadenosine polyphosphates directly relax porcine coronary arterial smooth muscle.

By use of front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, cytosolic Ca++ concentration ([Ca++]i) and force development were monitored simultaneously to determine the mechanisms of vasorelaxation induced by the diadenosine polyphosphates (APnA) diadenosine 5',5'''-P1, P4-tetraphosphate (AP4A) and diadenosine 5',5'''-P1,P5-pentaphosphate (AP5A). APnA concentration-dependently inhibited the sustained elevations of [Ca++]i and force induced by U-46619, a thromboxane A2 analog, in the presence of extracellular Ca++. APnA shifted the [Ca++]i-force relation curves of contractions induced by various concentrations of high K+ to the right. The AP4A-induced decreases in [Ca++]i and force were largely attenuated by tetrabutylammonium. The AP4A-induced decreases in force were attenuated by 4-aminopyridine and charybdotoxin. The AP5A-induced decreases in [Ca++]i and force were attenuated by tetrabutylammonium, 4-aminopyridine and charybdotoxin. In the absence of extracellular Ca++, APnA did not inhibit the transient elevations of [Ca++]i induced by histamine or caffeine. Both AP4A and AP5A increased intracellular cAMP content. We thus conclude that AP4A and AP5A relax the porcine coronary artery by decreasing [Ca++]i, possibly through the activation of K+ channels, but not through inhibition of intracellular Ca++ release and by decreasing the Ca++ sensitivity of the contractile machinery. These effects were considered to be mediated by cAMP.

Relationship of low-density lipoprotein particle size to plasma lipoproteins, obesity, and insulin resistance in Japanese men.

OBJECTIVE: To determine the clinical characteristics of patients with small low-density lipoprotein (LDL) particles among Japanese men with mild glucose intolerance and to investigate the relationship of LDL particle size to the levels of other plasma lipoproteins, obesity, insulin resistance, and blood pressure (BP). RESEARCH DESIGN AND METHODS: The subjects were 40 men with impaired glucose tolerance or diabetes treated by diet alone, and 40 healthy men matched for age and body mass index (BMI) were used as control subjects. LDL particle size was measured using gradient gel electrophoresis. RESULTS: Of the 40 patients with glucose intolerance, 19 had small LDL (particle size < 25.5 nm) compared with only 4 of the 40 control subjects. In the patients with small LDL, the plasma levels of cholesterol, triglycerides, and apolipoprotein B, the fasting serum immunoreactive insulin, and the waist-to-hip ratio were all higher than in the patients with normal LDL (particle size > or = 25.5 nm), while the high-density lipoprotein cholesterol level was lower. However, there were no significant differences in BMI, BP, or insulin sensitivity in a euglycemic clamp study between the small-LDL and normal-LDL subgroups. CONCLUSIONS: Japanese men with glucose intolerance frequently have small LDL, and this abnormality is associated with other dyslipoproteinemias and increased waist-to-hip ratio.