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OBJECTIVES: This study aimed to understand the status quo of medical treatments of the primary disease and pregnancy outcomes in patients with Takayasu arteritis (TAK) and children's birth outcomes. METHODS: This study retrospectively enrolled patients with TAK who conceived after the disease onset and were managed at medical facilities participating in the Japan Research Committee of the Ministry of Health, Labor, and Welfare for Intractable Vasculitis. RESULTS: This study enrolled 51 cases and 68 pregnancies 2019-2021. Of these, 48 cases and 65 pregnancies (95.6%) resulted in delivery and live-born babies. The median age of diagnosis and delivery was 22 and 31, respectively. Preconception therapy included prednisolone (PSL) in 51 (78.5%, median 7.5 mg/day), immunosuppressants in 18 (27.7%), and biologics in 12 (18.5%) pregnancies. Six cases underwent surgical treatment before pregnancy. Medications during pregnancy included PSL in 48 (73.8%, median: 9 mg/day), immunosuppressants in 13 (20.0%), and biologics in 9 (13.8%) pregnancies. Enlargement of an aneurysm was reported in one pregnancy, which might be associated with increased circulating plasma volume. TAK relapsed in 4 (6.2%) and 8 (12.3%) pregnancies during pregnancy and after delivery, respectively. Additionally, 13/62 (20.9%) preterm infants and 17/59 (28.8%) low birth weight infants were observed, and none had serious postnatal abnormalities. Of the 51 confirmed infants, 42 (82.4%) were exclusively breastfed or mixed with formula. CONCLUSION: Most pregnancies in TAK were manageable with PSL at ≤10 mg/day. Relapse during pregnancy and postpartum occurred in <20% of pregnancies.
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OBJECTIVES: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. METHODS: The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. RESULTS: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. CONCLUSIONS: This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.
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Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Anticuerpos Antifosfolípidos , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/etiologíaRESUMEN
Mycobacterium chelonae, a rapidly growing mycobacterium found in the natural environment, is known to cause localized lesions in the skin, soft tissue, and bone through traumatic inoculation, but widespread lesions are uncommon. We herein report an immunocompromised 79-year-old man suspected of having polyangiitis granulomatosis due to weight loss, epistaxis, and nasal crusts with impending septal perforation who was subsequently diagnosed with mucocutaneous and bone disease caused by widespread M. chelonae infection. Given these findings, clinicians should be aware of the tendency to develop unusual widespread lesions in immunocompromised patients, which can present a clinical picture similar to systemic vasculitides, such as granulomatosis with polyangiitis.
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Granulomatosis con Poliangitis , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium chelonae , Perforación del Tabique Nasal , Masculino , Humanos , Anciano , Granulomatosis con Poliangitis/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Perforación del Tabique Nasal/diagnóstico , Perforación del Tabique Nasal/etiología , Diagnóstico DiferencialRESUMEN
OBJECTIVE: This study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE. METHODS: We used mass cytometry with 25 marker panels for T-cell immune profiling in peripheral blood T cells (CD3+) from 22 patients with BEL-treated SLE and 20 controls with non-BEL-treated SLE. An unsupervised machine-learning clustering, FlowSOM, was used to identify 39 T-cell clusters (TCLs; TCL01-TCL39). TCLs (% of CD3+) showing significant (p<0.05) associations with BEL treatment (BEL-TCL) were selected by a linear mixed-effects model for comparing groups of time-series data. Furthermore, we analysed the association between BEL treatment and variations in regulatory T-cell (Treg) phenotypes, and the ratio of other T-cell subsets to Treg as secondary analysis. RESULTS: Clinical outcomes: BEL treatment was associated with a decrease in daily prednisolone use (coef=-0.1769, p=0.00074), and an increase in serum CH50 (coef=0.4653, p=0.003), C3 (coef=1.1047, p=0.00001) and C4 (coef=0.2990, p=0.00157) levels. Molecular effects: five distinct BEL-TCLs (TCL 04, 07, 11, 12 and 27) were identified. Among these, BEL-treated patients exhibited increased proportions in the Treg-like cluster TCL11 (coef=0.404, p=0.037) and two naïve TCLs (TCL04 and TCL07). TCL27 showed increased levels (coef=0.222, p=0.037) inversely correlating with baseline C3 levels. Secondary analyses revealed associations between BEL treatment and an increase in Tregs (coef=1.749, p=0.0044), elevated proportions of the fraction of Tregs with inhibitory function (fTregs, coef=0.7294, p=0.0178) and changes in peripheral helper T cells/fTreg (coef=-4.475, p=0.0319) and T helper 17/fTreg ratios (coef=-6.7868, p=0.0327). Additionally, BEL was linked to variations in T-cell immunoglobulin and mucin domain-containing protein-3 expression (coef=0.2422, p=0.039). CONCLUSIONS: The study suggests an association between BEL treatment and variations in T cells, particularly Tregs, in SLE pathologies involving various immune cells.
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Lupus Eritematoso Sistémico , Humanos , Subgrupos de Linfocitos T/metabolismo , Linfocitos T Reguladores , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
INTRODUCTION: Evidence on second-line agents for osteoporosis and osteopenia associated with glucocorticoid use after first-line bisphosphonate therapy is limited. We, therefore, examine the efficacy of denosumab on bisphosphonate-treated osteoporosis and osteopenia in Japanese systemic rheumatic disease (SRD) patients receiving glucocorticoids. MATERIALS AND METHODS: Glucocorticoid-treated SRD patients with a pre-existing fragility fracture, either lumbar spine (LS) or femoral neck (FN) bone mineral density (BMD) T-score of ≤ -2.5 or of ≤ -1.5 without a significant increase in BMD in the past year despite oral bisphosphonate therapy were enrolled in this study. They were randomized to switch to 60 mg subcutaneous denosumab every six months (switching group) or to continue the bisphosphonate (continuing group). The primary endpoint was the percent change from baseline in BMD at the LS and FN at week 52. RESULTS: Of the 39 subjects, 19 were assigned to the switching group and 20 to the continuing group. The switching group showed significant increases in LS BMD (5.7% vs. 1.1%, p = 0.002) and FN BMD (4.2% vs. -0.3%, p = 0.008) at week 52 than the continuing group, with a significant decrease in serum tartrate-resistant acid phosphatase 5b (-28.1% vs. 7.0%, p < 0.001) and improved patient satisfaction. CONCLUSION: Switching to denosumab demonstrated greater efficacy than continuing bisphosphonates in increasing BMD, inhibiting osteoclast activation, and enhancing patient satisfaction in Japanese bisphosphonate-treated osteoporosis and osteopenia patients with concomitant SRD receiving glucocorticoids.
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Conservadores de la Densidad Ósea , Osteoporosis , Enfermedades Reumáticas , Humanos , Difosfonatos/efectos adversos , Glucocorticoides/efectos adversos , Denosumab/efectos adversos , Conservadores de la Densidad Ósea/efectos adversos , Densidad Ósea , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Vértebras LumbaresRESUMEN
OBJECTIVES: We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Metotrexato/efectos adversos , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia Combinada , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVES: We aimed to identify associations between patterns of large-vessel lesions of large-vessel giant cell arteritis (LV-GCA) and treatment outcomes. METHODS: We extracted data on 68 newly diagnosed patients with LV-GCA from a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014. Patients with aortic lesions were identified based on the findings from contrast-enhanced computed tomography, magnetic resonance imaging, or positron emission tomography-computed tomography (Group 2, n = 49). Patients without aortic lesions were subdivided into LV-GCA with or without subclavian lesions defined as Group 1 (n = 9) or Group 3 (n = 10), respectively. The primary outcome evaluation was failure to achieve clinical remission by Week 24 and/or relapse within 104 weeks. RESULTS: The mean age and proportion of patients with cranial lesions and polymyalgia rheumatica in Group 2 were numerically lower than in the other two groups. Large-vessel lesions in Group 3 included carotid, pulmonary, renal, hepatic, or mesenteric lesions. The cumulative rate of poor treatment outcomes >2 years was 11.1%, 55.3%, and 88.0% in Groups 1, 2, and 3, respectively (by Kaplan-Meier analysis). The mean time to poor outcome was significantly different between the groups. CONCLUSIONS: Classification by subclavian and aortic lesions may be useful to determine treatment strategy.
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Arteritis de Células Gigantes , Polimialgia Reumática , Humanos , Arteritis de Células Gigantes/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To investigate the impact of dysphagia on long-term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis. METHODS: We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time-to-event analyses were used, including Kaplan-Meier curves with log-rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models. RESULTS: Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non-dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non-dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age-adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36-1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69-3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non-severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases. CONCLUSION: The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia.
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Trastornos de Deglución , Miositis por Cuerpos de Inclusión , Miositis , Deglución , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Humanos , Miositis/complicaciones , Miositis/diagnóstico , Miositis por Cuerpos de Inclusión/complicaciones , Miositis por Cuerpos de Inclusión/diagnóstico , Miositis por Cuerpos de Inclusión/terapia , Estudios RetrospectivosRESUMEN
AIM: Macrophage activation syndrome (MAS), a severe complication of systemic adult-onset Still's disease (AOSD), has been reported to occur during interleukin-6 (IL-6) inhibitor treatment. However, predictors for MAS development are unknown. Therefore, this study investigated predictive features for MAS development after starting IL-6 inhibitor treatment in systemic AOSD patients. METHOD: In a single-center retrospective study involving systemic AOSD patients who were refractory to high-dose glucocorticoids with immunosuppressants and started IL-6 inhibitor treatment between April 2008 and March 2020, we compared the baseline clinical features between patients who developed AOSD flare with MAS features (MAS group) and those who did not (non-MAS group) during IL-6 inhibitor treatment. RESULTS: Only tocilizumab was used as an IL-6 inhibitor. Six of 14 refractory systemic AOSD patients developed AOSD flares with MAS features during tocilizumab treatment, including 4 who developed them shortly after initiation. The MAS group had significantly lower neutrophil counts, fibrinogen, and higher IL-18/C-reactive protein (CRP) ratio at starting tocilizumab (baseline) than the non-MAS group. Before starting tocilizumab, neutrophil counts were trending downward and upward in the MAS and non-MAS groups, respectively, with significant differences in changes. Receiver operating characteristic analysis showed that baseline neutrophil counts and fibrinogen and their changes before tocilizumab treatment and baseline IL-18/CRP ratio had significant discriminatory abilities for subsequent MAS development. CONCLUSION: We identified baseline laboratory features associated with MAS development after initiating an IL-6 inhibitor in refractory systemic AOSD patients. These features may reflect the suppression of IL-6 signaling, and further suppression of IL-6 signaling might trigger early-onset MAS.
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Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Adulto , Proteína C-Reactiva , Fibrinógeno , Humanos , Interleucina-18 , Interleucina-6 , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Síndrome de Activación Macrofágica/etiología , Estudios Retrospectivos , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/tratamiento farmacológicoRESUMEN
OBJECTIVES: Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. METHODS: The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. RESULTS: Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. CONCLUSION: MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.
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Anticuerpos Monoclonales Humanizados , Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Biomarcadores , Ferritinas/sangre , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/tratamiento farmacológicoRESUMEN
Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophilic cytoplasm antibody (ANCA)-associated vasculitis characterized by asthma and eosinophilia. Although EGPA involves multiple organs, ocular involvement is infrequent and often carries a poor visual prognosis. We herein report a rare case of EGPA presenting with central retinal artery occlusion (CRAO) in which visual loss developed during treatment with anti-interleukin (IL)-5 receptor monoclonal antibody, and improvement in visual outcomes was attained after treatment combining high-dose oral corticosteroids, cyclophosphamide and an anticoagulant. Physicians should consider CRAO as an ophthalmic manifestation of EGPA in patients with severe eosinophilic asthma.
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Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Oclusión de la Arteria Retiniana , Anticuerpos Monoclonales , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Humanos , Receptores de Interleucina-5 , Oclusión de la Arteria Retiniana/inducido químicamente , Oclusión de la Arteria Retiniana/diagnóstico , Oclusión de la Arteria Retiniana/tratamiento farmacológicoRESUMEN
A case of eosinophilic granulomatosis with polyangiitis (EGPA) in which chronic rhinosinusitis (CRS) was improved with a reduction in the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer after the addition of mepolizumab is reported. A 55-year-old woman with EGPA receiving prednisolone 5 mg/day developed CRS with increases in the eosinophil count and the MPO-ANCA titer. Although it improved with prednisolone 15 mg/day in addition to mizoribine 150 mg/day, because azathioprine could not be taken orally due to side effects, it relapsed after prednisolone was tapered to 5 mg/day. There was no exacerbation of other vasculitis symptoms such as mononeuropathy multiplex. The patient was treated with additional mepolizumab 300 mg every 4 weeks, which resulted in the improvement of CRS and marked reductions of the eosinophil count and MPO-ANCA titer, and the reduction of prednisolone to 2 mg/day. Furthermore, even after tapering mepolizumab to 200 mg every 4 weeks, her condition remained stable without relapse of EGPA and without increases in the eosinophil count and MPO-ANCA titer. The clinical course of mepolizumab treatment in this patient suggests that the IL5-dependent inflammatory cascade is one of the factors contributing to the increase in MPO-ANCA in EGPA.
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Anti-melanoma differentiation-associated gene 5 (MDA-5) antibodies have widely known to be associated with amyopathic dermatomyositis with rapidly progressive interstitial lung disease (ILD). Although the triple combination therapy with high-dose glucocorticoids, cyclophosphamide, and a calcineurin inhibitor has been used to treat anti-MDA-5 antibody-positive rapidly progressive ILD, the prognosis of these patients remains poor despite this intensive therapy. Recently, several investigators have shown that combination therapy with tofacitinib might be potentially efficacious in those patients. We herein report a case of anti-MDA-5 antibody-positive dermatomyositis and associated ILD who had not responded to the triple therapy and tofacitinib 10 mg/day but markedly responded after increasing the dose of tofacitinib to 20 mg/day.
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Autoanticuerpos/sangre , Dermatomiositis/tratamiento farmacológico , Helicasa Inducida por Interferón IFIH1/inmunología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Piperidinas/administración & dosificación , Pirimidinas/administración & dosificación , Dermatomiositis/inmunología , Relación Dosis-Respuesta a Droga , Humanos , Enfermedades Pulmonares Intersticiales/inmunología , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis and is a rapidly progressive, life-threatening complication of adult-onset Still's disease (AOSD). An anti-IL-6 receptor monoclonal antibody, tocilizumab, has shown to be effective in the treatment of AOSD but may precipitate MAS in patients with AOSD. The precise mechanism of MAS developed during anti-cytokine biologic agents remains unknown, but selective inhibition of a subset of pathways could impact other immune signalling pathways and trigger MAS. We herein describe a case of AOSD with the opposite outcomes of tocilizumab therapy, remission and development of MAS, after tocilizumab treatment at the initial flare and the relapse. From the comparison of clinical characteristics and concomitant treatment around the time of starting tocilizumab in both flares, the type and intensity of concomitant immunosuppressive therapy might strongly affect MAS development during tocilizumab therapy.
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Anticuerpos Monoclonales Humanizados , Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Humanos , Síndrome de Activación Macrofágica/inducido químicamente , Enfermedad de Still del Adulto/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVE: To establish predictive models for mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) using a combination of initial serum biomarker levels. METHODS: The Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risk factors predictive of all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and those without anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between subgroups using the Breslow test. RESULTS: In the derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6) levels were identified as independent risk factors for mortality in both anti-MDA-5-positive and anti-MDA-5-negative patients. We then developed a prediction model based on anti-MDA-5 antibody status, CRP level, and KL-6 level, termed the "MCK model," to identify patients at low (<15%), moderate (15-50%), or high (≥50%) risk of mortality, based on the number of risk factors. The MCK model successfully differentiated cumulative survival rates in anti-MDA-5-positive patients (P < 0.01 for low versus moderate risk and P = 0.03 for moderate versus high risk) and in anti-MDA-5-negative patients (P < 0.001 for low versus moderate risk). The utility of the MCK model was replicated in the validation cohort. CONCLUSION: Our findings indicate that an evidence-based risk prediction model using CRP and KL-6 levels combined with anti-MDA-5 antibody status might be useful for predicting prognosis in patients with PM/DM-ILD.
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Dermatomiositis/sangre , Enfermedades Pulmonares Intersticiales/sangre , Modelos Teóricos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Dermatomiositis/complicaciones , Dermatomiositis/mortalidad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Pronóstico , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis (HLH) and is a life-threatening complication of adult-onset Still disease. MAS has been usually treated with high-dose glucocorticoid with additional immunosuppressive agents, such as cyclosporine. Etoposide has been used for the treatment of severe refractory MAS based on the successful results of HLH-2004 protocol in patients with mostly primary form of HLH. We herein describe a case of severe refractory MAS secondary to adult-onset Still disease in an elderly woman that inadequately responded to etoposide but remarkably responded to additional tocilizumab. Furthermore, short-term tocilizumab led her into remission and enabled tapering off glucocorticoids after 15 months. Tocilizumab may be effective for the treatment of refractory HLH after the failure of the etoposide-containing induction regimen.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome de Activación Macrofágica/complicaciones , Síndrome de Activación Macrofágica/tratamiento farmacológico , Terapia Molecular Dirigida , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/tratamiento farmacológico , Ciclosporina/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Etopósido/administración & dosificación , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Síndrome de Activación Macrofágica/diagnóstico , Índice de Severidad de la Enfermedad , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. RESULTS: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. CONCLUSION: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.
Asunto(s)
Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Arteritis de Células Gigantes/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Objectives: To investigate the prevalence and the consequence of tumor necrosis factor inhibitor (TNFi) cessation after clinical improvement in rheumatoid arthritis (RA) patients in clinical practice and predictors of flare after TNFi cessation.Methods: We retrospectively assessed the prevalence of TNFi cessation after achieving sustained improvement, disease flare and joint damage progression after TNFi cessation in consecutive RA patients who started TNFi due to insufficient response to methotrexate were studied. Predictors for flare after TNFi cessation were investigated using Cox regression analysis.Results: In 135 patients who started TNFi with methotrexate, 95 stopped TNFi after sustained improvement and continued methotrexate thereafter. Over 1 year, 33 patients had a flare and 26 restarted TNFi therapy. In 78 patients whose radiographs adequate for evaluation were available, 73 did not exhibit joint damage progression. Female gender, smoking, the interval from starting methotrexate to starting TNFi of more than 9 months and glucocorticoid use at starting TNFi were independently associated with shorter time to flare.Conclusion: Sixty-five percent of patients were successfully discontinued TNFi over 1 year. Radiographic joint damage progression was rare. Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation in patients with insufficient response to methotrexate.Key messageSuccessful TNF inhibitor cessation is achievable in two-third of RA patients after achieving sustained remission.Female gender and smoking may predispose to flare after TNF inhibitor cessation.Early intervention with TNF inhibitor may contribute to successful TNF inhibitor cessation.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Antirreumáticos/administración & dosificación , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/administración & dosificaciónRESUMEN
T-helper (Th)17.1 cells exhibit high pathogenicity in inflammatory diseases. This study aimed to identify the changes in the proportions of Th subsets, including Th17.1, which are associated with abatacept treatment response in Japanese patients with rheumatoid arthritis. On the basis of the results, we assessed whether Th17.1 is a potential cellular biomarker. Multicolor flow cytometry was used to determine the circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment. All the patients received abatacept treatment for 24 weeks; changes in disease activity score, including 28-joint count C-reactive protein, and responsiveness indicated by other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria (good and moderate responders and nonresponders). The correlation between the abatacept responses and the proportions of Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was performed to calculate the odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and nonresponders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 levels below the median value was 14.6 (95% confidence interval, 2.9-72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for predicting abatacept treatment response in Japanese patients. These novel findings may represent a significant step in the pursuit of precision medicine.