Mayu Saito

Influence of renal complications on the efficacy and adverse events of tacrolimus combination therapy in patients with systemic lupus erythematosus (SLE) during a maintenance phase: a single-centre prospective study

Objectives The study investigated whether renal complications affected the efficacy and safety of tacrolimus combination therapy in patients with systemic lupus erythematosus (SLE) during a maintenance phase. Methods Fifty-seven patients with SLE (A: 30 cases with renal complication, B: 27 cases without renal complications) were included. The presence of renal complications was defined as proteinuria ≥0.5 g/day and lupus nephritis on renal biopsy. Major outcome measures included SLE disease activity index (SLEDAI), steroid dose, serum anti-dsDNA Ab, C3 and creatinine (Cr) levels and estimated glomerular filtration rate (eGFR). The patients background factors included age, gender, disease duration and ACE-I/angiotensin II receptor blocker and statin therapies. We compared these outcome measures pre treatment and after 1 year of treatment. Results The SLEDAI and serum C3 levels improved in both groups from pretreatment period to post-treatment period: from 7.2±5.0 to 2.8±2.3 in A and 6.4±3.8 to 2.4±2.2 in B, p<0.001, and from 65.9±24.6 to 77.7±18.2 mg/dL in A and 81.8±23.0 to 90.6±19.4 mg/dL in B, p=0.002, respectively. The anti-dsDNA antibody level was reduced, and the serum Cr and eGFR levels were slightly elevated. No patients developed end-stage renal failure that required artificial dialysis. Conclusions Tacrolimus combination therapy had additive beneficial effects on reduced proteinuria and increased serum C3 levels in patients with SLE with renal complications during a maintenance phase.

Comparative Study of Infliximab Therapy and Methotrexate Monotherapy to Improve the Clinical Effect in Rheumatoid Arthritis Patients.

Objective We examined whether infliximab (IFX) therapy was more effective than methotrexate (MTX) monotherapy to achieve an improvement in depressive states in Rheumatoid Arthritis (RA) patients. Methods We examined 152 RA patients (72 IFX patients and 80 MTX patients). We conducted an open-label cohort study to evaluate the disease activity of RA (Simplified Disease Activity Index; SDAI), depressive states (Hamilton Rating Scale for Depression; HAM-D), Activity of Daily Living (ADL) (modified Health Assessment Questionnaire; mHAQ) and Quality of Life (QOL) [Short Form (SF)-36] in patients before and 6 months after receiving therapy. The HAM-D, SDAI, mHAQ and SF-36 scores after 6 months of therapy were measured as the outcomes. Results We analyzed 60 IFX patients and 53 MTX patients. The HAM-D scores significantly improved in both groups (p<0.001), but there was no significant difference in the effectiveness between the IFX and MTX therapies (p=0.792). The SDAI scores significantly improved in both groups after therapy (p<0.001), and IFX therapy was more effective than MTX therapy (p=0.004). The mHAQ and HAM-D scores also improved significantly in both groups after therapy (p<0.001), but no significant difference in the effectiveness between the IFX and MTX therapies was observed (p=0.272, 0.792). The scores of all 8 items of the SF-36 improved in both groups after therapy, but IFX therapy was more effective than MTX therapy in only 4 of the 8 items (p<0.05). Conclusion Both IFX and MTX therapy improved the clinical efficacy, ADL, QOL and depressive states. However, no significant differences regarding an improvement in the depressive states and ADL were observed between IFX therapy and MTX monotherapy.

A disintegrin and metalloproteinase (ADAM)-10 as a predictive factor for tocilizumab effectiveness in rheumatoid arthritis

Abstract Objectives: A disintegrin and metalloproteinase (ADAM)-10 is expressed in rheumatoid arthritis (RA). In this study, we focused on ADAM-10 as a predictive factor for the treatment with biologics in RA. Methods: The levels of ADAM-10 and fractalkine/CX3CL1 in RA and healthy controls serum were measured using enzyme-linked immunosorbent assays. Fifteen patients were treated with adalimumab (ADA), and 20 patients were treated with tocilizumab (TCZ). Results: ADAM-10 positively correlated with fractalkine/CX3CL1 in the sera of RA patients and was presented at a significantly higher level compared to that in normal serum (487 ± 80 pg/ml and 85 ± 33 pg/ml, respectively, p < 0.05). ADAM-10 highly correlates with fractalkine/CX3CL1 in the sera of RA patients. The level of ADAM-10 decreased after the treatment with TCZ but not with ADA. In addition, we found that the level of ADAM-10 in TCZ responders was significantly higher than that of the TCZ nonresponders at 24 weeks (619 ± 134 pg/ml and 109 ± 25 pg/ml, respectively). Multiple regression analysis showed that ADAM-10 was only identified as independent predictive variable for the improvement of DAS28 (ESR) at 24 weeks. Conclusions: ADAM-10 may be a predictor of the effectiveness of TCZ in treating RA.

Sex Differences in the Effects of a Biological Drug for Rheumatoid Arthritis on Depressive State

Objective : Sex-specific medicine has attracted attention in recent years, but no report on rheumatoid arthritis (RA) has examined sex differences in the effectiveness of biologics on activities of daily living (ADL), quality of life (QOL), or depressive state. Methods : The study subjects were 161 RA patients (female: 138; male: 23) attending regular doctor visits at our hospital. We compared the changes in disease activity, which was evaluated using the simplified disease activity index (SDAI), ADL (using the modified health assessment questionnaire; mHAQ), QOL (using short form-36; SF-36), and the Hamilton Depression Rating Scale (HAM-D) for RA patients between each sex over a six-month observation period while administering biologic treatment. Results : The female patients reported significant improvements in the following metrics: SDAI: from 22.1 ± 11.9 to 8.9 ± 7.8 (p < 0.001); mHAQ: from 0.46 ± 0.50 to 0.32 ± 0.45 (p < 0.001); and HAM-D: from 6.2 ± 4.8 to 3.8 ± 4.1 (p < 0.001). Moreover, all eight items of the SF-36 were significantly improved (p < 0.01). In contrast, the male patients improved on the SDAI (from 27.9 ± 11.7 to 12.7 ± 8.6 (p < 0.001)), but we did not observe significant improvements in the mHAQ or HAM-D scores or in any items on the SF-36. Conclusion : Both male and female patients with RA improved when using a biological drug. Sex differences in the improvement of depressive state were observed.

Predictor of the Simplified Disease Activity Index 50 (SDAI 50) at Month 3 of bDMARD Treatment in Patients with Long-Established Rheumatoid Arthritis

Objectives: The Simplified Disease Activity Index (SDAI) 50 has good agreement with European League Against Rheumatism (EULAR) response measures for early Rheumatoid Arthritis (RA). There have been reports on early RA, but not on long-established RA. In this study, we analysed the relationships between various baseline factors and SDAI 50 after three months of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) to determine the prognostic factors for long-established RA. Methods: Subjects were 260 RA patients who had been treated with bDMARDs for 3 months. The following characteristics were investigated: Patient backgrounds, the erythrocyte sedimentation rate (ESR), C-reactive protein and serum matrix metalloproteinase-3 levels, SDAI scores, and health assessment questionnaire disability index and short form-36 scores. As a primary outcome index, the SDAI response was defined as a 50% reduction in the SDAI score between baseline and 3 months (SDAI 50). Results: Baseline values of disease duration (odds ratio: 0.942, 95% CI: 0.902-0.984), smoking history (odds ratio: 2.272, 1.064-4.850), 28-tender joint count (odds ratio: 0.899, 0.827-0.977), evaluators global assessment (odds ratio: 1.029, 1.012-1.047) and ESR (odds ratio: 1.015, 1.001-1.030) were determined to be significant factors based on logistic regression analysis. Conclusion: Our study demonstrated that RA patients with shorter disease duration, no smoking, and higher RA disease activity are more likely to achieve SDAI 50 through bDMARD treatment.

AB0547 The prevalence and the risk factor of hypertension and dyslipidemia in systematic lupus erythematosus patients: exploratory research

Background Hypertension (HT) and dyslipidemia (DL) are the risk factors for all-cause mortality, cardiovascular and cerebrovascular disease, and end-stage renal disease in SLE patients 1). Neither disease activity nor chronic damage were associated with the metabolic syndrome in SLE patients 2) and there were few reports about the risk factors of HT and DL in Japanese SLE patients. Objectives We aimed to describe a prevalence of HT and DL and to identify the risk factor of HT and DL in Japanese SLE patients. Methods All SLE patients visited at Showa University Hospital and Okayama University Hospital from January 2016 to September 2016, were enrolled in a cross-sectional study. SLE patients who satisfied American College of Rheumatology (ACR) criteria were included. HT was defined as usage of anti-HT drugs and DL was defined as usage of anti-DL drugs. We performed descriptive statistics and binomial logistic regression analysis to identify the risk factors of HT and DL. Variables considered possible risk factors were BMI, drinking status, smoking status (current smoking), current daily dose of glucocorticoids, past maximum dose of glucocorticoids, lupus nephritis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI). Results In total, 244 participants were enrolled. The mean age was 46.2±15.3 years, and 222 (91%) were female. The mean current daily dosage of glucocorticoids was 6.7±5.9 mg, and the mean SLEDAI-2K was 5.0±5.2 and the mean SLICC/ACR-DI was 1.3±1.7. The prevalence of HT and DL were 29.1% (71/244) and 22.1% (54/244). Both HT and DL were confirmed in 11.9% (29/244) patients. On binomial logistic regression analysis, BMI (regression coefficients (β)= -0.095; 95% confidential interval (CI) = -0.173 to -0.020), drinking status (β =0.443; 95% CI =0.000 to 0.879), past maximum dosage of glucocorticoids (β= -0.018; 95% CI = -0.036 to -0.004) and lupus nephritis (β= -0.727; 95% CI =0.230 to 1.241) were identified as the significant independent risk factors of HT. On the other hand, only age (β= -0.030; 95% CI = -0.055 to -0.006) was identified as the independent risk factor of DL. There was no independent risk factor of having both DL and HT. Conclusions Our results could help to identify patients at higher risk of HT and DL. References Hsin-Hui Yu. et al. Statin reduces mortality and morbidity in systemic lupus erythematosus patients with hyperlipidemia: A nationwide population-based cohort study. Atherosclerosis. 2015;243:11–18. Cecilia P Chung. Et al. High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors. Ann Rheum Dis. 2007;66:208–214. Disclosure of Interest None declared

FRI0153 Relationship between Serum Oxytocin Levels and Disease Activity, Depressive State, ADL, and QOL in Patients with Rheumatoid Arthritis

Background Oxytocin, which is also called a happy hormone, has been reported to be related to various conditions including depressive state. However, the positioning of oxytocin in rheumatoid arthritis (RA) remains unclear. Objectives The objective of this study was to investigate the relationship between serum oxytocin levels and disease activity, depressive state, activity of daily life (ADL), and quality of life (QOL) in RA. Methods The study included 20 patients with RA who received treatment with a biological agent. We measured the following items before and at 6 months after the start of treatment. The baseline characteristics included the age, sex, prednisolone dose, methotrexate dose, duration of disease, anti-cyclic citrullinated peptide antibody (anti-CCP antibody), rheumatoid factor (RF), serum matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate, and C-reactive protein (CRP). The disease activity of rheumatoid arthritis was assessed using the Simplified Disease Activity Index (SDAI), depressive state using Hamilton Depression Rating Scale (HAM-D), ADL using the Health Assessment Questionnaire (HAQ), and QOL using the 36-Item Short Form Health Survey (SF-36). Serum oxytocin levels were determined by enzyme-linked immunosorbent assay (ELISA). The correlation between each item and the serum oxytocin levels were examined. Results The serum oxytocin levels before the start of treatment were correlated with RF (r=−0.529), HAQ (r=0.446), HAM-D (r=0.508), and among the 8 categories of the SF-36, physical function (r=−0.676), role function (physical) (r=−0.801), pain (r=−0.506), general health perception (r=−0.787), role function (emotional) (r=−0.844), and mental health (MH) (r=−0.516). On the other hand, the serum oxytocin levels did not correlate with the SDAI (r=−0.078). The serum oxytocin levels after the start of treatment were correlated with the age (r=−0.549), SDAI (r=−0.539), HAQ (r=0.813), HAM-D (r=0.584), and all of the SF-36 categories except for MH (r=0.038) (r>0.4). Other items did not correlate to the serum oxytocin levels. Conclusions The serum oxytocin levels before the start of treatment were correlated with depressive state, ADL, and QOL but not with disease activity. Those after the start of treatment were correlated with the SDAI, depressive state, ADL, and QOL. Disclosure of Interest Y. Miwa Grant/research support from: Tanabemitsubishi, Chugai, phizer, Ono, R. Takahashi: None declared, S. Isojima: None declared, M. Saito: None declared, Y. Miura: None declared, S. Ishii: None declared, Y. Ikari: None declared, T. Tokunaga: None declared, T. Kasama: None declared, Y. Toyoshima: None declared, K. Inagaki: None declared

SAT0085 Study of Prognostic Factors Associated with Death from Pneumocystis Pneumonia Complicated by Collagen Diseases

Background Corticosteroids and immunosuppressant are now widely used as a treatment for collagen diseases, and complications of pneumocystis pneumonia (PCP) have become a problem. Objectives We study prognostic factors associated with death from PCP complicated by collagen diseases. Methods We conducted a retrospective analysis on the basis of the medical records of 38 patients with PCP complicated by collagen diseases. For background factors, age, gender, baseline diseases, medications at the time of hospital admission (dose of steroids, immunosuppressant), the presence of complications (respiratory diseases, diabetes, chronic kidney disease), smoking history, trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis were studied. For laboratory data, CBC (including lymphocyte count), serum LDH, albumin, creatinine, CRP, KL-6, SP-D, IgG level, IgA, IgM, (1,3)-β-D-glucan, arterial blood gas, and sputum PCP-DNA (tested by PCR) at the time of hospital admission were investigated. The eGFR was calculated using creatinine value, age, and gender. We also studied treatment methods after hospitalization (TMP-SMX use, change from TMP-SMX to pentamidine, pulsed-steroid therapy, intratracheal intubation, managing in ICU) and hospitalization period. Results In laboratory data, the group of non-survivors had a higher creatinine (0.88±0.38 mg/dl vs. 1.16±0.38, p=0.045), a lower albumin (3.13±0.50 g/dl vs. 2.71±0.38, p=0.031), a higher CRP (7.8±7.0 mg/dl vs. 18.9±8.8, p=0.014), a lower IgA (274±108 mg/dl vs. 174±54, p=0.013), a higher serum SP-D (173±106 vs. 285±285, p=0.047), and a lower PaO2/FiO2 (P/F) ratio (268±99 mmHg vs. 147±98, p=0.025). For sputum PCP (by PCR), all patients were positive in the group of non-survivors, but only 18 out of 31 survivors (58%) were positive. All patients in the group of non-survivors underwent pulsed-steroid therapy, but it was assumed that the therapy was performed in order to treat severe respiratory failure because the patients who resulted in death had a low P/F ratio and severely poor respiratory status. On the other hand, as background factors, there was no significant difference. Conclusions We newly identified prognostic factors associated with death from PCP, which are a low serum albumin and cholinesterase at the time of PCP diagnosis, decreased pulmonary diffusing capacity, and significantly high rate of intratracheal intubation and managing in ICU; in this study, male, older age, a high serum creatinine, a high CRP, a low IgA, a high SP-D, a low P/F ratio, and sputum PCP positive (by PCR) were newly identified as the poor prognostic factors. Disclosure of Interest None declared

AB0328 A Study on Characteristics of Rheumatoid Arthritis Patients Achieving Clinical Remission After 6 Months of Treatment with Biologic Agents

Background Biologic agents are highly effective for rheumatoid arthritis (RA); however, not all cases achieve clinical remission. It is difficult to predict the effectiveness before starting the treatment. Objectives To study predictive factors for clinical remission, which is one of the treatment goals in RA, after using biologic agents for 6 months. Methods The subjects were 333 RA patients treated with biologic agents. The following patients characteristics were investigated: age, gender, the type of biologic agents, the number of previous drugs, disease duration, baseline steroid dosage, MTX dosage, serum RF, MMP-3, ACPA, TNF-α, and IL-6. For evaluation we used SDAI for RA disease activity, HAQ for ADL, Short Form (SF)-36 for QOL, and Hamilton Depression Rating Scale (HAM-D) or Self-rating depression scale (SDS) for depression status, respectively. Clinical remission was defined by SDAI3.3 after 6 months of treatment. The subjects were divided into two groups: patients with SDAI3.3 and patients with SDAI >3.3 at 6 months, and a retrospective study was conducted. 101 patients were excluded from the study due to loss to 6-month follow-up, and a total of 232 patients were analyzed. Results Compared with a group of RA patients without clinical remission (n=167), a group of patients with clinical remission (n=65) had younger age (50.0±15.5 vs. 59.6±14.1, p<0.001), lower steroid dosage (1.9±2.4 mg/day vs. 4.3±3.8, p<0.001), lower serum MMP-3 (151±197 ng/ml vs. 239±244, p<0.05), lower serum TNF-α (28.4±57.7 pg/ml vs. 76.0±193.8, p=0.028), and lower serum IL-6 (12.5±22.8 pg/ml vs. 60.6±180.8, p=0.017) at baseline. In addition, those who achieved remission showed lower SDAI (17.9±11.7 vs. 28.0±13.7, p<0.001), lower HAQ (0.26±0.38 vs. 0.71±0.63, p<0.001), higher SF-36 (p<0.05 in all categories), lower SDS (38.0±9.5 vs. 42.5±9.7, p=0.0061), and lower HAM-D (4.7±3.6 vs. 6.4±5.2, p<0.05) at baseline. On the other hand, there was no significant difference on gender, the types of biologic agents, the order of drugs used in the treatment, MTX dosage, disease duration, serum RF, and ACPA. Conclusions It was suggested that RA patients with lower disease activity, lower dosage of steroid, younger age, higher ADL and QOL, lower depression scores, and lower serum TNF-α and IL-6 at baseline are more likely to achieve clinical remission with biologic treatment. Disclosure of Interest Y. Miwa Grant/research support from: Astellas Pharm Inc., Mitsubishi Tanabe Pharma Corporation, AbbVie CK, Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd., and Eizai Co., Ltd., R. Takahashi: None declared, S. Isojima: None declared, T. Isozaki: None declared, M. Saito: None declared, N. Oguro: None declared, S. Nishimi: None declared, T. Kasama: None declared, K. Oh: None declared, Y. Toyoshima: None declared, K. Inagaki: None declared