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Objectives To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. Methods Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Results Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP Conclusions While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.

Objectives To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. Methods Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Results Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP Conclusions While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.

Objective Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. Methods We built gene expression predictive models in blood B cells, CD4(+) and CD8(+) T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. Results TWAS identified 171 genes for SLE (p<1.0x10(-5)); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7x10(-8)). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5x10(-9)) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. Conclusions Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

A novel patient cluster in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may be identified in Japan. We performed multiple correspondence and cluster analysis regarding 427 clinically diagnosed AAV patients excluding eosinophilic granulomatosis with polyangiitis. Model 1 included the ANCA phenotype, items of the Birmingham Vasculitis Activity Score, and interstitial lung disease; model 2 included serum creatinine (s-Cr) and C-reactive protein (CRP) levels with model 1 components. In seven clusters determined in model 1, the ANCA-negative (n=8) and proteinase 3-ANCA-positive (n=41) groups emerged as two distinct clusters. The other five myeloperoxidase-ANCA-positive clusters were characterized by ear, nose, and throat (ENT) (n=47); cutaneous (n=36); renal (n=256), non-renal (n=33); and both ENT and cutaneous symptoms (n=6). Four clusters in model 2 were characterized by myeloperoxidase-ANCA negativity (n=42), without s-Cr elevation (<1.3 mg/dL) (n=157), s-Cr elevation (1.3 mg/dL) with high CRP (>10 mg/dL) (n=71), or s-Cr elevation (>= 1.3 mg/dL) without high CRP (<= 10 mg/dL) (n=157). Overall, renal, and relapse-free survival rates were significantly different across the four clusters in model 2. ENT, cutaneous, and renal symptoms may be useful in characterization of Japanese AAV patients with myeloperoxidase-ANCA. The combination of s-Cr and CRP levels may be predictive of prognosis.

Objectives The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor alpha (TNF-alpha)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods In this multicentre randomised trial, patients with IFX-naive rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-alpha until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) <= 3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI <= 3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

Background It is not elucidated that there is treatment-related damage in elderly patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods Elderly (≥ 75 years of age) patients were enrolled from two nationwide prospective inception cohort studies. The primary outcome was 12-month treatment-related Vasculitis Damage Index (VDI) score. Secondary outcomes included serious infections within 6 months, total VDI score, remission, and relapse. Patient characteristics and outcomes were compared across three different initial glucocorticoid (GC) dose groups: high-dose, prednisolone (PSL) ≥ 0.8 mg/kg/day; medium-dose, 0.6 ≤ PSL < 0.8 mg/kg/day; and low-dose, PSL < 0.6 mg/kg/day. Results Of the 179 eligible patients, the mean age was 80.0 years; 111 (62%) were female. The mean Birmingham Vasculitis Activity Score was 16.1. Myeloperoxidase-ANCA findings were positive in 168 (94%) patients, while proteinase 3-ANCA findings were positive in 11 (6%). The low-dose group was older and had higher serum creatinine levels than the other groups. There were no statistically significant intergroup differences in remission or relapse, whereas serious infection developed more frequently in the high-dose (29 patients [43%]) than the low-dose (13 patients [22%]) or medium-dose (10 patients [19%]) groups (p = 0.0007). Frequent VDI items at 12 months included hypertension (19%), diabetes (13%), atrophy and weakness (13%), osteoporosis (8%), and cataracts (8%). Logistic regression analysis revealed that GC dose at 12 months (odds ratio, 1.14; 95% confidence interval, 1.00–1.35) was a predictor for diabetes. Conclusion A reduced initial GC dose with rapid reduction might be required to ensure the safe treatment of elderly AAV patients.

Objectives The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor alpha (TNF-alpha)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods In this multicentre randomised trial, patients with IFX-naive rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-alpha until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) <= 3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI <= 3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

Objectives: To identify predictive factors for remission by tocilizumab monotherapy in rheumatoid arthritis (RA) patients. Methods: This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH). The primary endpoint was DAS28-ESR remission (<2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (Delta mTSS/year) was also assessed as an endpoint. The effect of clinical parameters at baseline on remission was estimated by logistic regression analysis. Results: In SWITCH (n = 96), CRP, SAA, RF, and DAS28 at baseline showed predictive value for DAS28 remission in unadjusted analysis. Adjusted analysis confirmed SAA and DAS28 as predictive factors, with SAA having the highest value (ROC-AUC = 0.731). Furthermore, structural remission (Delta mTSS/year <= 0.5) rate was significantly higher in patients with SAA of < 50.0 mu g/mL than other patients. In contrast, in ADD-ON (n = 98), only DAS28 showed predictive value for DAS28 remission. In patients with SAA < 50.0 mu g/mL, both DAS28 remission and structural remission rate were comparable between SWITCH and ADD-ON. Conclusion: RA patients with low SAA levels at baseline may benefit similarly from tocilizumab with and without methotrexate.