Avacopan's potential to decrease MPO-ANCA titres concurrent with ameliorated activity in ANCA-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, is effective in microscopic polyangiitis via the inhibition of neutrophil priming induced by C5a. However, the exact effect of avacopan on the production of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is yet to be clearly established. This report presents a microscopic polyangiitis patient without major organ damage where high levels of MPO-ANCA persisted with high-dose steroid therapy and azathioprine, but the addition of avacopan led to a reduction in MPO-ANCA titres. The present case implies that avacopan-mediated inhibition of C5a may lead to a reduction in MPO-ANCA levels, thereby potentially ameliorating the pathophysiology of ANCA-associated vasculitis. Nevertheless, the impact of avacopan on MPO-ANCA production cannot be asserted solely based on this report; therefore, further examination is necessary through subgroup analysis using data from larger-scale studies.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

OBJECTIVE: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. METHODS: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. RESULTS: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. CONCLUSION: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Myeloid-derived suppressor cell-derived osteoclasts with bone resorption capacity in the joints of arthritic SKG mice.

Background: Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells with immunosuppressive functions. It is known that MDSCs are expanded at inflammatory sites after migrating from bone marrow (BM) or spleen (Sp). In chronic inflammatory diseases such as rheumatoid arthritis (RA), previous reports indicate that MDSCs are increased in BM and Sp, but detailed analysis of MDSCs in inflamed joints is very limited. Objective: The purpose of this study is to characterize the MDSCs in the joints of mice with autoimmune arthritis. Methods: We sorted CD11b+Gr1+ cells from joints (Jo), bone marrow (BM) and spleen (Sp) of SKG mice with zymosan (Zym)-induced arthritis and investigated differentially expressed genes (DEGs) by microarray analysis. Based on the identified DEGs, we assessed the suppressive function of CD11b+Gr1+ cells from each organ and their ability to differentiate into osteoclasts. Results: We identified MDSCs as CD11b+Gr1+ cells by flow cytometry and morphological analysis. Microarray analysis revealed that Jo-CD11b+Gr1+ cells had different characteristics compared with BM-CD11b+Gr1+ cells or Sp-CD11b+Gr1+ cells. Microarray and qPCR analysis showed that Jo-CD11b+Gr1+ cells strongly expressed immunosuppressive DEGs (Pdl1, Arg1, Egr2 and Egr3). Jo-CD11b+Gr1+ cells significantly suppressed CD4+ T cell proliferation and differentiation in vitro, which confirmed Jo-CD11b+Gr1+ cells as MDSCs. Microarray analysis also revealed that Jo-MDSCs strongly expressed DEGs of the NF-κB non-canonical pathway (Nfkb2 and Relb), which is relevant for osteoclast differentiation. In fact, Jo-MDSCs differentiated into osteoclasts in vitro and they had bone resorptive function. In addition, intra-articular injection of Jo-MDSCs promoted bone destruction. Conclusions: Jo-MDSCs possess a potential to differentiate into osteoclasts which promote bone resorption in inflamed joints, while they are immunosuppressive in vitro.

Low Hounsfield unit values on computed tomography as a potential predictor of vertebral fracture in patients with rheumatoid arthritis: The KURAMA cohort study.

OBJECTIVE: Hounsfield units (HU) measured using computed tomography (CT) have gained considerable attention for the detection of osteoporosis. This study aimed to investigate whether opportunistic CT could predict vertebral fractures in patients with rheumatoid arthritis (RA). METHODS: A total of 233 patients with RA who underwent chest CT were included in this study. The HU values of the anterior 1/3 of the vertebral bodies based on the sagittal plane at T11-L2 after reconstruction were measured. The incidence of vertebral fractures was investigated with respect to the HU value. RESULTS: Vertebral fractures were identified in 32 patients during a mean follow-up period of 3.8 years. In patients who experienced vertebral fractures within 2 years of CT imaging, the HU values of the vertebral bodies (T11-L2) were lower than those in patients who did not experience fractures. Receiver operating characteristic curve analysis identified that a T11 HU value of <125 was a risk factor for vertebral fracture within 2 years. Multivariate analysis showed that a T11 HU value of <125 and the existence of prevalent vertebral fractures were significant risk factors for fracture. CONCLUSION: HU measurements of the anterior 1/3 of the vertebral body are a potential predictor for vertebral fractures in patients with RA.

Significant association of HLA-A26 with uveitis and gastrointestinal involvement in patients with Behçet's disease in a multicenter study.

OBJECTIVES: Specific HLA haplotypes are associated with Behçet's disease (BD). Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in BD have not been well demonstrated, we aimed to examine them. METHODS: This multicenter, cross-sectional, observational study enrolled patients with BD who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score. RESULTS: Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harboring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (p = 0.03) and coexistence of uveitis and gastrointestinal involvement (p = 0.002), and higher Krause scores (p = 0.02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (p = 0.001) and gastrointestinal involvement in patients with uveitis (p = 0.001). CONCLUSIONS: Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.

Effect of high disease activity on spinal sagittal malalignment in patients with rheumatoid arthritis.

OBJECTIVE: Atlantoaxial subluxation is a well-known serious complication encountered in patients with rheumatoid arthritis (RA). However, it is unknown whether RA affects global spinal alignment. The aim of this study was to investigate whether high disease activity in patients with RA exacerbates spinal sagittal malalignment. METHODS: The authors included 197 patients with RA who were followed up for > 2 years; standing spinal radiographs were obtained in all patients. Patients were divided into persistent moderate disease activity/high disease activity (pMDA/HDA; n = 64) and non-pMDA/HDA (n = 133) groups based on the disease activity at follow-up visits. Radiographic parameters assessed included pelvic incidence, pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and C7 sagittal vertical axis (SVA). RESULTS: Over an average 5-year follow-up, increases in SVA, PT, and TK and a decrease in LL were observed. The pMDA/HDA group had a larger increase in PT and a higher incidence of vertebral fractures than the non-pMDA/HDA group. After adjusting variables using propensity score matching, the authors still found a higher rate of increase in PT (0.79°/year vs 0.01°/year, p = 0.001) in the pMDA/HDA group than in the non-pMDA/HDA group. This trend remained consistent even when patients who developed vertebral fractures were excluded. CONCLUSIONS: Spinal sagittal alignment deteriorates over time in patients with RA. High disease activity in RA exacerbates spinal deformity.

Anti-aminoacyl tRNA synthetase antibodies showing the discrepancy between enzyme-linked immunosorbent assay and RNA-immunoprecipitation.

Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, n = 52) and discrepant (negative on RNA-IP, n = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (p < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

Identification of the VLDLR locus associated with giant cell arteritis and the possible causal role of low-density lipoprotein cholesterol in its pathogenesis.

OBJECTIVES: To elucidate the association between genetic variants and the risk of giant cell arteritis (GCA) via large-scale genome-wide association studies (GWAS). In addition, to assess the causal effect of a specific molecule by employing the obtained GWAS results as genetic epidemiological tools. METHODS: We applied additional variant quality control to the publicly available GWAS results from the biobank of the United Kingdom (UKBB) and Finnish (FinnGen), which comprised 532 cases vs 408 565 controls and 884 cases vs 332 115 controls, respectively. We further meta-analyzed these two sets of results. We performed two-sample Mendelian randomization (MR) to test the causal effect of low-density lipoprotein (LDL) cholesterol on the risk of GCA. RESULTS: The MHC class II region showed significant associations in UKBB, FinnGen, and the meta-analysis. The VLDLR region was associated with GCA risk in the meta-analysis. The T allele of rs7044155 increased the expression of VLDLR, decreased the LDL cholesterol level, and decreased the disease risk. The subsequent MR results indicated that a 1-standard deviation increase in LDL cholesterol was associated with an increased risk of GCA (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.01-1.45; p = 0.04). CONCLUSIONS: Our study identified associations between GCA risk and the MHC class II and VLDLR regions. Moreover, LDL cholesterol was suggested to have a causal effect on the risk of developing GCA.

Attenuation of HOIL-1L ligase activity promotes systemic autoimmune disorders by augmenting linear ubiquitin signaling.

Linear ubiquitin chains, which are generated specifically by the linear ubiquitin assembly complex (LUBAC) ubiquitin ligase, play crucial roles in immune signaling, including NF-κB activation. LUBAC comprises catalytic large isoform of heme-oxidized iron regulatory protein 2 ubiquitin ligase 1 (HOIL-1L) interacting protein (HOIP), accessory HOIL-1L, and SHANK-associated RH domain-interacting protein (SHARPIN). Deletion of the ubiquitin ligase activity of HOIL-1L, an accessory ligase of LUBAC, augments LUBAC functions by enhancing LUBAC-mediated linear ubiquitination, which is catalyzed by HOIP. Here, we show that HOIL-1L ΔRING1 mice, which exhibit augmented LUBAC functions upon loss of the HOIL-1L ligase, developed systemic lupus erythematosus (SLE) and Sjögren's syndrome in a female-dominant fashion. Augmented LUBAC activity led to hyperactivation of both lymphoid and myeloid cells. In line with the findings in mice, we sought to identify missense single nucleotide polymorphisms/variations of the RBCK1/HOIL-1L gene in humans that attenuate HOIL-1L ligase activity. We found that the R464H variant, which is encoded by rs774507518 within the RBCK1/HOIL-1L gene, attenuated HOIL-1L ligase activity and augmented LUBAC-mediated immune signaling, including that mediated by Toll-like receptors. We also found that rs774507518 was enriched significantly in patients with SLE, strongly suggesting that RBCK1/HOIL-1L is an SLE susceptibility gene and that augmented linear ubiquitin signaling generated specifically by LUBAC underlies the pathogenesis of this prototype systemic autoimmune disease.

TAFRO syndrome is associated with anti-SSA/Ro60 antibodies, in contrast to idiopathic castleman disease.

TAFRO syndrome is an acute systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly. There have been increasing reports that TAFRO is a disease distinct from idiopathic multicentric Castleman disease and that TAFRO patients may be positive for anti-SSA antibodies. To assess anti-SSA antibody positivity and the clinical characteristics of the two diseases, we retrospectively compared 7 TAFRO and 10 iMCD patients in our hospital. The mean age of onset of TAFRO and iMCD was 48.0 (interquartile range [IQR], 41-53) and 45.0 (IQR, 35-53) years, respectively. The TAFRO and iMCD groups had 6 (86%) and 4 (40%) male patients, respectively, and the following pretreatment laboratory values: platelet count, 3.8 (IQR, 2.2-6.4) and 35.5 (IQR, 22.2-42.8) × 104/µL, respectively; C-reactive protein, 10.2 (IQR, 6.8-21.4) and 9.5 (IQR, 6.2-13.6) mg/dL, respectively; IgG, 1431 (IQR, 1112-1815) and 4725 (IQR, 3755-5121) mg/dL, respectively. RNA immunoprecipitation (5 cases for anti-SSA) or protein array (5 cases for anti-SSA/Ro60) detected anti-SSA antibodies in six (86%) TAFRO patients but not in iMCD patients; it did not detect anti-SSB antibodies in any of the patients. None of the patients were diagnosed with Sjögren syndrome. All iMCD patients treated with tocilizumab (TCZ) responded well. Meanwhile, two of six TAFRO patients treated with TCZ showed inadequate responses; thus, both patients were switched to rituximab, following which they achieved remission. TAFRO and iMCD have different clinical features. TAFRO may be categorized as a severe phenotype of the anti-SSA antibody syndrome.

Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey.

OBJECTIVE: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab. METHODS: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed. RESULTS: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy. CONCLUSION: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment.

Monocyte-derived transcriptomes explain the ineffectiveness of abatacept in rheumatoid arthritis.

BACKGROUND: The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA. METHODS: Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results. RESULTS: Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway. CONCLUSIONS: Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.

Management and treatment outcomes of rheumatoid arthritis in the era of biologic and targeted synthetic therapies: evaluation of 10-year data from the KURAMA cohort.

BACKGROUND: Advances in rheumatoid arthritis (RA) treatment, highlighted by biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), have altered the paradigm of RA treatment in the last decade. Therefore, real-world clinical evidence is needed to understand how treatment strategies and outcomes have changed. METHODS: Using an observational cohort of RA from 2012 to 2021, we collected cross-sectional data of RA patients annually to analyze a trend in RA management. For patients who initiated b/tsDMRDs, we evaluated treatment outcomes between b/tsDMARDs. Mixed-effect models were applied to examine the statistical implications of changes over time in treatment outcomes with a background adjustment. RESULTS: We analyzed annual cross-sectional data from 5070 patients and longitudinal data from 1816 patients in whom b/tsDMARDs were initiated between 2012 and 2021. b/tsDMARD use increased, whereas glucocorticoid use decreased from 2012 to 2021. Disease activity and functional disability measures improved over time. The percentage of tsDMARD prescriptions considerably increased. All b/tsDMARDs showed clinical improvements in disease activity and functional disability. Statistically, TNFi showed better short-term improvements in b/tsDMARD-naïve patients, while IL6Ri demonstrated significant long-term benefits. IL6Ri had better retention rates in switched patients. After adjustment for patient characteristics, the annual change of RA disease activity and functional disability fared significantly better from 2012 to 2021. CONCLUSIONS: With the development of new RA therapeutics, overall treatment outcomes advanced in the past decade.

IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Predictive value of baseline concomitant glucocorticoid for abatacept-mediated long-term inhibition of radiographic progression: insights from the KURAMA cohort.

Abatacept (ABT) is a biological disease-modifying antirheumatic drug (bDMARDs) for rheumatoid arthritis (RA) when conventional synthetic DMARDs are ineffective. We aimed to evaluate the long-term effects of ABT on joint destruction in patients treated for over 2 years. Radiographic progression was evaluated using the van der Heijde-modified Total Sharp Score (mTSS) by two rheumatologists at ABT initiation and after 2 years. Multivariate logistic regression analysis was used to identify factors associated with structural remission, defined as the mean annual change in mTSS ≤0.5. Among the 111 patients included, 48 discontinued, and 63 continued ABT treatment until radiographic evaluation was performed. The rate of patients who achieved estimated TSS REM (yearly progression of van der Heijde modified total Sharp scores ≤0.5) was significantly lower in ABT-dropouts than in the ABT-continued group (69% vs. 48%, p = .0336 by Fisher's exact test). Among the continued ABT cases, concomitant glucocorticoid treatment at ABT initiation was the strongest negative predictive factor of estimated TSS REM in univariate and multivariate logistic regression analyses. Radiographic progression after ABT administration should be evaluated separately for dropout and non-dropout cases. Glucocorticoids at the initiation of ABT may serve as a predictive factor for joint destruction in long-term ABT use.

Comparative effectiveness of biological disease-modifying antirheumatic drugs and Janus kinase inhibitor monotherapy in rheumatoid arthritis.

OBJECTIVES: To examine the effectiveness and drug tolerability of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitor (JAKi) monotherapy in patients with rheumatoid arthritis (RA) in a multicentre cohort study. METHODS: Patients with RA initiated with bDMARD/JAKi monotherapy without conventional synthetic DMARDs were included. Monotherapy regimens were categorised as interleukin-6 receptor inhibitors (IL-6Ri), cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4Ig), JAKi, or tumour necrosis factor inhibitors (TNFi). Multiple propensity score-based inverse probability weighting (IPW) was used to reduce selection bias. Linear mixed-effect models with IPW were used to examine changes in the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) at 24 weeks, and drug retention was compared among monotherapy using IPW Cox proportional hazards models. RESULTS: A total of 849 treatment courses from 635 patients were included (IL-6Ri, 218; CTLA4Ig, 183; JAKi, 92; TNFi, 356). The difference in change in DAS28-ESR at week 24 as the primary outcome was -0.93 (95% CI: -1.20 to -0.66) lower in the IL-6Ri group than TNFi, while that of CTLA4Ig and JAKi was similar with that of TNFi (-0.20 [-0.48 to 0.08], -0.25 [-0.67 to 0.16], respectively). IL-6Ri use was associated with significantly lower overall drug discontinuation than TNFi use (hazard ratio = 0.55 [0.39-0.78], P = 0.001). Similar retention rates were identified among CTLA4Ig and JAKi compared to TNFi. CONCLUSION: In the analysis with IPW to reduce selection bias, IL-6Ri monotherapy was superior to TNFi monotherapy in terms of effectiveness and drug retention. No significant differences were identified between CTLA4Ig, JAKi, and TNFi monotherapy.