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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.
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Anemia , Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de la Interleucina-6 , Estudios de Cohortes , Anemia/tratamiento farmacológico , Anemia/etiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéuticoRESUMEN
OBJECTIVES: To determine the current retention rate of mepolizumab (MPZ) and identify factors associated with drug retention in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in the Kansai multicentre cohort (REVEAL cohort). METHODS: Sixty patients diagnosed with EGPA and treated with MPZ between December 2016 and June 2023 were enrolled. The clinical characteristics, including laboratory data, treatments administered, and disease course outcomes were collected retrospectively. The patients were stratified into MPZ continuation (n=53) and discontinuation (n=7) groups, and drug retention was statistically compared using the log-rank test. RESULTS: The median age of patients was 54.5 years, with 55% females, and 33% antineutrophil cytoplasmic antibody-positive at disease onset. MPZ exhibited a retention rate of 78.7% after five years. The reasons for discontinuation included treatment of coexisting diseases, inadequate response, and remission. Patient characteristics at disease onset were comparable between the groups. Patients receiving immunosuppressants (IS) before MPZ introduction demonstrated significantly higher retention rates (P = 0.038). During the final observation, the MPZ continuation group had a lower vasculitis damage index score (P = 0.027). CONCLUSIONS: MPZ exhibited a high 5-year retention rate, particularly in patients requiring IS. This study implies that long-term use of MPZ may mitigate irreversible organ damage.
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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.
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OBJECTIVE: The objective of this study was to evaluate nailfold videocapillaroscopy (NVC) as a useful tool for assessing the disease activity of ANCA-associated vasculitis (AAV). METHODS: This study enrolled 51 patients with AAV and 21 healthy controls. We scored NVC findings semiquantitatively, and compared them between AAV patients and controls. We examined the association of NVC findings with disease activity indicators, histopathological findings of skin biopsies, and high-resolution CT (HRCT) scores in AAV. Additionally, we repeatedly rated the NVC findings 3 months after immunosuppressive therapy. RESULTS: Of the 51 enrolled patients, 36 (70.6%) showed a microangiopathy pattern and 4 (7.8%) showed a scleroderma pattern in AAV. The scores for microhaemorrhage, capillary loss, neoangiogenesis, and tortuosity were significantly higher in the AAV group than in the control group. NVC abnormalities correlated with the severity of skin, lung and kidney involvement. The scores of giant capillaries significantly correlated with the total BVAS and the chest BVAS; the scores of capillary loss correlated with the chest BVAS and the renal BVAS. The scores of microhaemorrhage significantly correlated with perivascular inflammatory cell infiltrations in the upper dermis of the purpura and tended to correlate with the total ground-glass opacity and consolidation scores on HRCT. In addition, capillary loss scores had a significant positive correlation with serum creatinine levels. Additionally, the microhaemorrhage scores were significantly reduced after 3 months of immunosuppressive therapy. CONCLUSION: In AAV patients, NVC abnormalities are significantly associated with disease severity. This result suggests that NVC is a useful tool for assessing the disease activity and treatment response in AAV.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Enfermedades Vasculares , Humanos , Angioscopía Microscópica , Piel , Capilares/diagnóstico por imagen , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico por imagen , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Uñas/irrigación sanguíneaRESUMEN
OBJECTIVE: This study aimed to establish prediction models for respiratory-related mortality in microscopic polyangiitis (MPA) complicated by interstitial lung disease (ILD) using clinical characteristics. METHODS: We enrolled patients with MPA with ILD between May 2005 and June 2021 in a multicentre cohort of Japanese patients with MPA (REVEAL cohort). We evaluated the demographic, clinical, laboratory, radiological findings, treatments, and the presence of honeycombing 1 cm above the diaphragm using chest high-resolution computed tomography (HRCT) on admission. We explored the risk factors predictive of respiratory-related mortality. RESULTS: Of 115 patients, 26 cases died of respiratory-related diseases during a median follow-up of 3.8 years. Eighteen patients (69%) died due to respiratory infection, three (12%) had diffuse alveolar hemorrhage (DAH), and five (19%) had exacerbation of ILD. In univariate analysis, older age, lower percent forced vital capacity (%FVC), lower percent diffusing capacity of carbon monoxide (%DLco), and the presence of honeycombing in the right lower lobe were identified as risk factors. Additionally, in multivariate analysis adjusted for age and treatment, %FVC, %DLco, and the presence of honeycombing in the right lower lobe were independently associated with respiratory-related mortality. We created prediction models based on the values of %FVC, %DLco, and presence of honeycombing on chest HRCT (MPF model). The 5-year respiratory-related death-free rate was significantly different between patients with MPA with ILD stratified by the number of risk factors based on the MPF model. CONCLUSIONS: Our study indicates that the MPF model may help predict respiratory-related death in patients with MPA with ILD.
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This study aimed to evaluate the risk factors for end-stage renal disease (ESRD) in microscopic polyangiitis (MPA). In total, 74 patients with MPA were enrolled, and we compared the baseline clinical characteristics and disease activity between MPA patients who have progressed to ESRD and those without ESRD to select predictive factors for ESRD. Out of 74 patients, 12 patients (16.2%) had ESRD during follow-up. Serum C4 levels were significantly higher in MPA patients who have progressed to ESRD than in those without ESRD (p = 0.009). Multivariate analyses revealed that high serum creatinine levels (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.25-15.5) and high serum C4 levels (OR 1.24, 95% CI 1.03-1.49) were risk factors for ESRD. Using receiver operating characteristic analysis, the cut-off value for initial serum C4 levels and serum creatinine levels were 29.6 mg/dL and 3.54 mg/dL, respectively. Patients with MPA with a greater number of risk factors (serum C4 levels > 29.6 mg/dL and serum creatinine levels > 3.54 mg/dL) had a higher ESRD progression rate. Serum C4 levels were significantly positively correlated with serum creatinine levels and kidney Birmingham vasculitis activity score (p = 0.02 and 0.04, respectively). These results suggest that serum C4 levels are useful tools for assessing renal disease activity and prognosis in MPA.
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Fallo Renal Crónico , Poliangitis Microscópica , Humanos , Poliangitis Microscópica/complicaciones , Complemento C4 , Creatinina , Estudios Retrospectivos , Fallo Renal Crónico/etiología , Proteínas del Sistema Complemento , BiomarcadoresRESUMEN
This multicenter retrospective study aimed to clarify the prognostic factors for mortality and changes in treatment modalities and disease activities after the onset of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA). Data regarding the clinical background, treatment modalities, and disease activity indicators of RA at the onset of PCP (baseline), and 6 months and 12 months after treatment were extracted. Of the 37 patients with RA-PCP (median age, 69 years; 73% female), chemical prophylaxis was administered to 8.1%. Six patients died during PCP treatment. The serum C-reactive protein (CRP) levels and the prednisolone (PDN) dose at baseline in the PCP death group were significantly higher than those in the survivor group. Multivariate analysis using a Cox regression model showed that PDN dose at baseline was a predictor of death from PCP in patients with RA. During the 12 months from baseline, the RA disease activity significantly decreased. A high dose of corticosteroids for RA may result in a poor prognosis when PCP is complicated. In the future, preventive administration techniques must be established for patients with RA who need PCP prevention.
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Artritis Reumatoide , Pneumocystis carinii , Neumonía por Pneumocystis , Humanos , Femenino , Anciano , Masculino , Neumonía por Pneumocystis/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Cohortes , Pronóstico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Prednisolona/uso terapéuticoRESUMEN
OBJECTIVES: This multicenter, retrospective study evaluated the effectiveness of add-on methotrexate (MTX) or iguratimod (IGU) in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors (JAKis). METHODS: Forty-five patients were treated with new additional MTX (n = 22) or IGU (n = 23) and followed for 6 months. Patients' background is as follows: age, 59.2 years; disease activity score of 28 joints with C-reactive protein (DAS28-CRP), 3.4; clinical disease activity index, 15.7; biological disease-modifying antirheumatic drug (DMARD)-switched cases, 77.8%; first JAKi cases, 95.6%; and JAKi treatment: tofacitinib (n = 25), baricitinib (n = 17), upadacitinib (n = 2), and peficitinib (n = 1) for 9.6 months. RESULTS: Thirty-five patients continued the combination therapy for 6 months without a significant change in concomitant glucocorticoid or other conventional synthetic DMARDs. DAS28-CRP (MTX, 3.6 to 2.6, p < 0.05; IGU, 3.3 to 2.1, p < 0.001) and clinical disease activity index (MTX, 16.7 to 8.8, p < 0.05; IGU, 14.6 to 6.5, p < 0.01) improved significantly from baseline. Using the 2019 European League Against Rheumatism criteria, 45.4% (MTX) and 39.1% (IGU) achieved moderate or good response and 40.9% (MTX) and 39.1% (IGU) achieved American College of Rheumatology 20% improvement criteria. CONCLUSIONS: Adding MTX or IGU to inadequate responders of JAKi can be considered as a complementary treatment.
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Antirreumáticos , Artritis Reumatoide , Inmunosupresores , Inhibidores de las Cinasas Janus , Metotrexato , Humanos , Metotrexato/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Estudios Retrospectivos , Sulfonamidas , Inmunosupresores/uso terapéutico , Quimioterapia Combinada , Inhibidores de las Cinasas Janus/uso terapéutico , Resultado del Tratamiento , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más AñosRESUMEN
The aim of this multi-centre retrospective study was to clarify the prognostic factors for respiratory-related death in patients with interstitial lung disease (ILD) complicated rheumatoid arthritis (RA). Patient background data, treatment regimen, and disease activity indicators of RA and ILD at baseline, 6 months after the diagnosis of ILD, and at the last follow-up visit were extracted. A total of 312 patients with RA-ILD (17 patients who died from respiratory-related causes and 295 survivors) were included. Patients who died from respiratory-related causes had an older median age, a higher proportion of being male, and a higher anti-cyclic citrullinated peptide antibody positivity rate than survivors (p = .0001, .038, and .016, respectively); they also had significantly higher baseline serum levels of Krebs von den Lungen-6 (KL-6) than survivors (p = .013). Patients who died from respiratory-related causes showed significantly greater changes in serum KL-6 levels between the 6-month time point and the last visit [ΔKL-6 (6 months - last)] than survivors (p = .011). Multivariate analysis showed that the ΔKL-6 (6 months - last) corrected by disease duration was a predictor of respiratory-disease-related death in patients with RA-ILD (p < .0001). Long-term increase in serum KL-6 levels is associated with respiratory-disease related death in patients with RA-ILD.
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Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Humanos , Masculino , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Pronóstico , Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnósticoRESUMEN
Interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure and often presents as pulmonary fibrosis. Although it is treated using immunosuppressive and antifibrotic agents, the beneficial effects of these agents remain limited. Thus, the development of new therapeutic strategies for lung fibrosis is crucial. Mesenchymal stem/stromal cells (MSCs) have multilineage differentiation potential; additionally, they have anti-inflammatory and antifibrotic effects as well as the ability to modulate the immune response and modify the microenvironment at the site of engraftment. Numerous adipose-derived MSCs (ASCs) are present in the adipose tissue. Heparin and low-molecular-weight heparin (LMWH) mediate the secretion of several cytokines and growth factors with cell migratory and antifibrotic effects. This study aimed to confirm the therapeutic effect of LMWH-activated ASCs on ILD. Mouse ASCs (mASCs) were cultured in an LMWH-supplemented medium. LMWH significantly increased the number of mASC and enhanced their migratory, anti-inflammatory, and antifibrotic effects. Furthermore, mice with bleomycin-induced pulmonary fibrosis were intravenously administered LMWH-activated mASCs. The relative mRNA expression of inflammation-related genes in ILD lungs was significantly lower in the treatment group than in the pathological model group. Our findings suggest that LMWH-activated mASC administration reduces lung fibrosis.
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Trasplante de Células Madre Mesenquimatosas , Fibrosis Pulmonar , Tejido Adiposo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Bleomicina/efectos adversos , Citocinas , Heparina , Heparina de Bajo-Peso-Molecular/efectos adversos , Ratones , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , ARN Mensajero , Células del EstromaRESUMEN
BACKGROUND: Management of infectious complications in pregnant women receiving immunosuppressive therapy for systemic lupus erythematosus (SLE) is important. Maternal infection with cytomegalovirus (CMV) often causes congenital CMV infection in the foetus. Thus far, there are only few reports on congenital CMV infection after maternal reactivation in patients with SLE. We report the first case of congenital CMV infection after maternal primary infection in a patient with SLE. CASE PRESENTATION: A 19-year-old Japanese primigravida with SLE received treatment with prednisolone 3 mg/day and azathioprine 75 mg/day at conception. At 7 weeks of gestation, she suddenly developed fever and had decreased white blood cell and platelet counts and elevated aspartate aminotransferase and alanine aminotransferase levels. These clinical findings led to a diagnosis of SLE exacerbation. The prednisolone dose was increased to 15 mg/day, and hydroxychloroquine (200 mg/day) was administered. Consequently, all clinical findings normalised at 12 weeks. At 19 weeks, foetal ultrasound findings revealed oligohydramnios, brain hypoplasia, ventriculomegaly and hyperechogenic bowel. Maternal serological test results indicated increased CMV-specific IgG and IgM levels, low IgG avidity (26%), and positive CMV antigenemia. The foetus was diagnosed with symptomatic congenital CMV infection transmitted from the maternal primary infection. After counselling about the severe prognosis of the foetus, the mother decided to terminate her pregnancy and underwent artificial abortion at 21 weeks. DISCUSSION: The foetus of a mother with SLE who is receiving immunosuppressive therapy may be at increased risk of transmission and aggravation of congenital CMV infection; thus, preventive management and screening for congenital CMV infection during pregnancy are recommended for such patients. Maternal CMV infection shows clinical findings similar to those of SLE exacerbation, and careful differential diagnosis by maternal serological evaluation and foetal ultrasound scans is required.
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Infecciones por Citomegalovirus , Lupus Eritematoso Sistémico , Prednisolona/farmacología , Complicaciones Infecciosas del Embarazo , Anticuerpos Antivirales/inmunología , Citomegalovirus/genética , Citomegalovirus/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto JovenRESUMEN
OBJECTIVES: This study investigated postpartum bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) receiving long-term glucocorticoid (GC) therapy, assessed risk factors for decreased postpartum BMD, and evaluated change of BMD after postpartum initiation or restarting of osteoporosis drugs. METHODS: We retrospectively examined 30 SLE patients who gave birth and 31 non-pregnant SLE patients. In the postpartum SLE patients, BMD was measured after delivery and 1 year later. Multivariate analyses were performed to assess risk factors for decreased BMD in postpartum SLE patients. RESULTS: Patient age at pregnancy was 34.5 ± 4.5 years, and SLE duration was 9.7 ± 6.0 years. The mean prednisolone dose was 9.7 ± 3.2 mg/day. Body mass index (BMI) was 21.6 ± 2.2 kg/m2, with 13 women (43%) experiencing their first delivery. Postpartum BMD was 1.080 ± 0.120 g/cm2 in the lumbar spine and 0.834 ± 0.109 g/cm2 in the total hip. Bone loss occurred in six patients (21%) in the lumbar spine and 11 patients (37%) in the total hip. Postpartum lumbar spine BMD was significantly reduced compared to that in the non-pregnant group (1.143 ± 0.120 g/cm2, p = 0.048). Multivariate analysis identified gestational age and low BMI before pregnancy as risk factors for hip bone loss. CONCLUSION: Postpartum BMD significantly decrease in SLE patients receiving long-term GC, and low BMI before pregnancy was a risk factor for the decrease. Preconception care to prevent osteoporosis and that regularly monitors BMD after delivery are needed.
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Lupus Eritematoso Sistémico , Osteoporosis , Absorciometría de Fotón , Índice de Masa Corporal , Densidad Ósea , Femenino , Glucocorticoides/efectos adversos , Humanos , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Periodo Posparto , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Although interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure, the efficiency of current therapies is limited. This study aimed to investigate the effects of human MIKO-1 (hMIKO-1), a hybrid protein that suppresses the abnormal activation of macrophages, on murine macrophage function and its therapeutic effect in a mouse model of bleomycin-induced ILD (BLM-ILD). To this end, the phenotype of thioglycolate-induced murine peritoneal macrophages co-cultured with hMIKO-1 was examined. The mice were assigned to normal, BLM-alone, or BLM + hMIKO-1 groups, and hMIKO-1 (0.1 mg/mouse) was administered intraperitoneally from day 0 to 14. The mice were sacrificed on day 28, and their lungs were evaluated by histological examination, collagen content, and gene expression levels. hMIKO-1 suppressed the polarization of murine macrophages to M2 predominance in vitro. The fibrosis score of lung pathology and lung collagen content of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. The expression levels of TNF-α, IL-6, IL-1ß, F4/80, and TIMP-1 in the lungs of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. These findings indicate that hMIKO-1 reduces lung fibrosis and may be a future therapeutic candidate for ILD treatment.
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Enfermedades Pulmonares Intersticiales , Fibrosis Pulmonar , Animales , Bleomicina/toxicidad , Colágeno/metabolismo , Modelos Animales de Enfermedad , Humanos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismoRESUMEN
This study aimed to elucidate the pathomechanism of peripheral neuropathy (PN) in microscopic polyangiitis (MPA) and to identify biomarkers useful for diagnosis and severity assessment. Patients with MPA (n = 37) and other non-inflammatory neurological diseases (ONDs; n = 12) were enrolled, and the peripheral nerves of all patients were evaluated using nerve conduction studies. We compared the clinical characteristics and 14 serum biomarker profiles among patients with MPA and PN, MPA without PN, and ONDs. Patients with MPA had a higher prevalence of motor neuropathy than patients with ONDs. Among the patients with MPA, those with motor neuropathy had significantly higher total Birmingham Vasculitis Activity Scores and serum levels of C-reactive protein (CRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 than patients without motor neuropathy. Multivariable analyses adjusted for age, serum CRP level, and diabetes mellitus showed that high serum levels of TIMP-1 were independently related to a diagnosis of motor neuropathy in MPA. Additionally, there were significant negative correlations between the serum levels of TIMP-1 and compound muscle action potential amplitudes. Serum levels of TIMP-1 may be associated with the pathomechanism of motor neuropathy in MPA and could be a useful biomarker for diagnosing and evaluating the severity of motor neuropathy in MPA.
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Poliangitis Microscópica , Enfermedades del Sistema Nervioso Periférico , Humanos , Inhibidor Tisular de Metaloproteinasa-1 , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Biomarcadores , Proteína C-ReactivaRESUMEN
OBJECTIVES: We prospectively evaluated whether the addition of iguratimod (IGU) could sustain clinical remission in rheumatoid arthritis (RA) patients after tapering of methotrexate (MTX). METHODS: The study included 47 patients; 25 patients in the MTX maintenance group, and 22 patients in the IGU addition group who were treated with additional IGU and tapering of MTX dose. Clinical efficacy and safety were evaluated at 12, 24, and 36 weeks. RESULTS: In the IGU addition group, the dose of MTX could be reduced from 8.6 ± 2.4 mg/week at baseline to 4.7 ± 2.2 mg/week at 36 weeks (p < .001). Clinical remission was maintained (disease activity score [DAS]28-ESR 1.48 ± 0.63 at baseline and 1.69 ± 0.76 at 36 weeks, p = .911), and disease activity remained low (clinical disease activity index [CDAI] 2.4 ± 1.5 at baseline and 3.1 ± 3.4 at 36 weeks, p = .825). The US-GLOSS score significantly decreased from 9.2 ± 5.3 at baseline to 6.4 ± 4.3 at 36 weeks (p = .034). In the IGU addition group, two patients discontinued IGU because of stomatitis and three patients relapsed during the follow-up period (flare rate: 15.0%). There was no significant difference in RA disease activity at 36 weeks between the two groups. CONCLUSION: Additional use of IGU can effectively reduce the MTX dose required by patients during clinical remission without inducing a flare.
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Antirreumáticos , Artritis Reumatoide , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Cromonas , Quimioterapia Combinada , Humanos , Metotrexato/uso terapéutico , Inducción de Remisión , Sulfonamidas , Resultado del TratamientoRESUMEN
OBJECTIVES: We retrospectively compared the therapeutic effects of combination therapy with prednisolone (PSL) and oral tacrolimus (TAC) or azathioprine (AZA) on progressive interstitial pneumonia with systemic sclerosis (SSc-PIP). METHODS: The effects of PSL (0.2-0.5 mg/kg/day) and TAC (3 mg/day) or AZA (1-2 mg/kg/day) therapies (n = 18) were evaluated for short (12 months) and long (36 months or more) periods. RESULTS: In the short period, IP improved in 6 and 5 patients and was stable in 12 and 13 patients in the TAC and AZA groups, respectively. In the long period, 11 patients were followed up in the TAC group and 12 in the AZA group. IP improved in 4 and 2 patients and was stable in seven and nine in the TAC and AZA groups, respectively. The rates of evolution of total fibrosis score, and those corrected by disease duration for the long period, in the TAC group were significantly lower than those in the AZA group (p = .017 and .025, respectively). CONCLUSION: The inhibitory effect of PSL and TAC combination therapy on the progression of fibrosis in SSc-PIP may be superior to that of PSL and AZA in the long period.
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Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Azatioprina/uso terapéutico , Quimioterapia Combinada , Fibrosis , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Prednisolona/uso terapéutico , Estudios Retrospectivos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Tacrolimus/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: Microscopic polyangiitis (MPA) is often complicated by interstitial lung disease (ILD); however, biomarkers that can be used to diagnose and predict the progression of MPA-ILD have not been identified. In this study, we evaluated various serum biomarkers in MPA-ILD to assess their diagnostic and predictive performance. METHODS: We enrolled 49 patients with anti-neutrophil cytoplasmic antibody (ANCA)+ MPA and 10 healthy controls, with 32 of the MPA patients also presenting ILD. The presence of ILD was assessed by high-resolution CT and evaluated by ground-glass opacity and fibrosis score. We compared 16 biomarker profiles among MPA-ILD patients, those without ILD, and healthy controls and extracted biomarkers with higher levels in MPA-ILD groups to determine correlations with disease activity and other biomarkers. Three lung biopsies were examined by haematoxylin-eosin staining and immunostaining. RESULTS: Initial serum C-C motif chemokine ligand 2 (CCL2) levels were significantly higher in the MPA-ILD group than those of the MPA group, and were significantly higher in MPA-ILD patients 1 year after immunosuppressive therapy than those before treatment. Initial serum CCL2 levels positively correlated with an increased fibrosis score during the year after treatment and with initial serum platelet-derived growth factor levels. Immunohistochemical staining showed intense CCL2 signals in CD68+/CD163+ macrophages and metaplastic epithelial cells in MPA-ILD lungs. CONCLUSION: CCL2 is associated with MPA-ILD pathogenesis and suggested its potential efficacy as a useful marker for diagnosing and predicting MPA-ILD progression. Therefore, targeting CCL2 in alveolar CD68+/CD163+ macrophages might represent a therapeutic intervention in ANCA+ MPA-ILD.
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Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Quimiocina CCL2/sangre , Enfermedades Pulmonares Intersticiales/sangre , Poliangitis Microscópica/sangre , Receptores de Superficie Celular/sangre , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/inmunología , Biomarcadores/sangre , Biopsia , Estudios de Casos y Controles , Quimiocina CCL2/inmunología , Progresión de la Enfermedad , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Macrófagos/inmunología , Masculino , Poliangitis Microscópica/inmunología , Poliangitis Microscópica/patología , Valor Predictivo de las Pruebas , Receptores de Superficie Celular/inmunología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: We aimed to investigate the efficacy of anti-IL-6 receptor antibody (aIL-6) and other biologic disease-modifying antirheumatic drugs (bDMARDs), such as TNF inhibitor and CTLA4-Ig in the treatment of rheumatoid arthritis (RA) in patients with knee joint involvement. METHODS: We retrospectively analyzed 1059 treatment courses of patients with RA who visited our hospitals and were treated with bDMARDs. We categorized them into two groups, with or without knee joint involvement. We investigated the clinical disease activity index (CDAI) at baseline and 12 weeks after the initiation of bDMARDs. We compared the improvement of the markers between aIL-6 and other bDMARDs. RESULTS: Treatment with aIL-6 significantly increased ΔCDAI (n = 91, 15.4 ± 1.1; mean ± SEM) in patients with knee joint involvement, compared to other bDMARDs (n = 232, 11.0 ± 0.7) at 12 weeks (P = 0.006). Following the multivariate analysis adjusted by the CDAI levels at baseline, age, gender, concomitant use of methotrexate, and the first use of bDMARDs, ΔCDAI levels were significantly higher in aIL-6, compared to other bDMARDs (P = 0.02). However, there was no significant difference in ΔCDAI improvement between aIL-6 (n = 162, 5.9 ± 0.6) and other bDMARDs (n = 573, 6.2 ± 0.4) in patients without swollen knee joints. ΔCDAI levels were equally increased in patients with shoulder and elbow joint involvement. CONCLUSION: aIL-6 was more effective in the patients with RA and knee joint involvement, compared to other bDMARDs.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Articulación de la Rodilla , Receptores de Interleucina-6/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: We explored rheumatoid arthritis (RA) disease activity before, during, and after pregnancy in patients treated with tight control and investigated the association between disease activity in the postpartum period and those before and during pregnancy. METHODS: We retrospectively reviewed disease activity and medications of 27 patients before pregnancy, at every trimester, and in the postpartum period. RESULTS: Prednisolone was administered to 33% of patients with a median dose of 0 (0-2.5) mg/day and biologic agents was 78% in the third trimester. The median remission rates during all periods were the Disease Activity Score-28-C-reactive Protein assessed with three variables (DAS28-CRP-3) 85%, Simplified Disease Activity Index (SDAI) 55%, and Clinical Disease Activity Index (CDAI) 54%. Although SDAI and CDAI decreased significantly from before pregnancy to the first trimester and increased from the third trimester to the postpartum period, DAS28-CRP-3 did not change during all periods. Although SDAI and CDAI before and during pregnancy were significantly correlated with those in the postpartum period, DAS28-CRP-3 was not. CONCLUSIONS: Tight control before pregnancy suppressed RA disease activity during pregnancy and in the postpartum period. SDAI/CDAI before and during pregnancy were predictive for disease activity in the postpartum period.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Periodo Posparto/fisiología , Prednisolona/uso terapéutico , Índice de Severidad de la Enfermedad , Adulto , Factores Biológicos/uso terapéutico , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Embarazo , Inducción de Remisión , Proyectos de Investigación , Estudios RetrospectivosRESUMEN
OBJECTIVES: To elucidate the serum cytokine profile and address the pathomechanism of interstitial lung disease (ILD) complicated with PM/DM. METHODS: Forty patients with PM/DM-ILD were enrolled, and principal components analysis and cluster analysis were performed to classify patients into subgroups. Additionally, we compared cytokine profiles between the survivors and dead patients and between anti-melanoma differentiation-associated gene 5 antibody- and anti-aminoacyl tRNA synthetase antibody-positive ILD patients. We also examined the association of various cytokines with disease activity indicators and prognosis of ILD. RESULTS: The principal components analysis data allowed classification of the cytokine profile into three groups: group 1, neutrophilic and M1-macrophage-driven cytokines; group 2, type 1 Th cell-driven and M2-macrophage-induced cytokines; and group 3, M2-macrophage-driven cytokines. Cluster analysis showed the presence of PM/DM-ILD patient groups with high or low levels of total cytokines. Ninety percent of patients who died of ILD were included in clusters with high cytokine levels. Serum cytokine levels of all groups were significantly higher in the anti-melanoma differentiation-associated gene 5 antibody-positive patients than in the anti-aminoacyl tRNA synthetase antibody-positive patients. Groups 1 and 2 significantly correlated with known factors for poor prognosis, such as serum ferritin levels and alveolar-arterial oxygen difference. Serum cytokine levels of patients in group 1 were significantly higher initially and at 2 and 4 weeks in those who died. CONCLUSION: These findings suggested that the activation of monocytes, macrophages and type 1 Th cells, and neutrophils play roles in the pathomechanism of PM/DM-ILD, and group 1 cytokines could be useful biomarkers for predicting prognosis of PM/DM-ILD.