Overwhelming response to tumor necrosis factor-? inhibitor infliximab “innovator” versus adalimumab “bio-similar” in a previously therapy naive adult: A case report

Therapeutic options for the patient with spondyloarthritis (SpA) are limited. The pharmacotherapy for SpA comprises immunomodulator/suppressive drugs. In this case report, we describe the case of a 29-year-old postgraduate resident in medicine who was diagnosed with SpA and was managed by a combination of various disease-modifying drugs such as methotrexate and sulfasalazine, and immunomodulators such as systemic corticosteroids and tumor necrosis factor (TNF)-? inhibitors. After a series of therapeutic trials with them, the chimeric TNF blocker infliximab led to significant clinical improvement in symptoms and reduction in disease activity

Perfil epidemiológico de pacientes com Hemofilia A e doenças associadas ao uso do fator VIII/recombinante / Epidemiological profile of patients with Hemophilia A and diseases associated with the use of factor VIII/recombinant

Introdução: o Brasil é o quarto país em casos de Hemofilia A. O tratamento é infundir o fator de coagulação ausente. Reações ao uso do fator podem incluir manifestações alérgicas, doenças virais transfusionais e aloanticorpos. Objetivo: analisar o perfil epidemiológico de pacientes com Hemofilia A, e as doenças associadas ao uso do fator VIII e fator VIII recombinante. Metodologia: estudo transversal descritivo e retrospectivo. A coleta de dados foi realizada nos prontuários de pacientes com diagnóstico de hemofilia A, preenchidos com mais de 70% das informações, na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Brasil. Resultados: o Ministério da Saúde identificou no Estado do Amazonas, o registro de 276 indivíduos com diagnóstico de Hemofilia A. Incluídos para análise neste estudo 164 prontuários. Características sociodemográficas: homens 99,4%, adolescentes (28%) e jovens (26,8%); de cor parda 67,1%, ensino fundamental incompleto 28,6% e, exercendo a ocupação de estudante 42,7%. Condição clínica: 36,6% classificados com hemofilia A grave. Todos os pacientes tiveram diagnóstico clínico e laboratorial. O parentesco mais comum é o de irmãos com 35,3%. Sintomas predominantes: hemartrose 45,4%; dor 31,9%; edema 24% e artropatia 8,5%. O fator VIII recombinante, administrado em 34,8% dos pacientes, enquanto o fator VIII plasmático em 28,0%. Administrados doses de 2000UI a 2999UI. As complicações: artralgia 77,4% e hemorragia 77,4%. Conclusão: cuidados qualificados dos profissionais de saúde auxiliam na prevenção de complicações sérias, resultando em qualidade de vida ao hemofílico.

Introduction: Brazil is the fourth country in cases of Hemophilia A. The treatment is to infuse the missing clotting factor. Reactions to the use of the factor can include, allergic manifestations, transfusion viral diseases and alloantibodies. Objective: analyze the epidemiological profile of patients with Hemophilia A, and the diseases associated with the use of factor VIII and recombinant factor VIII. Methodology: descriptive and retrospective cross-sectional study. Data collection was carried out in the medical records of patients diagnosed with hemophilia A, filled with more than 70% of the information, at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas, Brazil. Results: in the Ministry of Health of Brazil, it was identified, for the State from Amazonas, the registry of 276 individuals diagnosed with Hemophilia A. Included in the analysis for this study, 164 medical records. Sociodemographic characteristics: male, 99.4%, adolescents (28%) and young people (26.8%), brown skin color, 67.1%, incomplete elementary school, 28.6%, and working as a student, 42.7%. Clinical condition: 36.6% classified with severe hemophilia A. All patients had a clinical and laboratory diagnosis. The most common kinship is that of brothers, 35.3%. Predominant symptoms: hemarthrosis 45.4%, pain 31.9%, edema 24% and arthropathy 8.5%. Recombinant factor VIII, administered in 34.8% of patients, while plasma factor VIII in 28.0%. Doses of 2000 IU to 2999 IU were administered. Complications: arthralgia 77.4% and hemorrhage 77.4%. Conclusion: qualified care by health professionals helps to prevent serious complications, resulting in quality of life for the hemophiliac.

Clinical efficacy of immune checkpoint inhibitor plus vascular endothelial growth factor inhibitor in the first-line treatment of advanced unresectable hepatocellular carcinoma / 中华消化外科杂志

In the past decade, rapid breakthroughs have been made in the systemic treat-ment of advanced unresectable hepatocellular carcinoma. Single systemic therapy has little effect on controlling tumor local recurrence and distant metastasis, and the combination modality therapy is the treatment for the majority of patients with advanced hepatocellular carcinoma. The change of tumor microenvironment is the research hotspot of antitumor therapy at present. Targeted therapy, immunotherapy and radiotherapy can lead to a change in the tumor microenvironment of primary hepatic carcinoma. The synergistic effect of combined therapy is particularly important. The authors report the clinical efficacy of programmed death ligand-1 inhibitor plus vascular endothelial growth factor inhibitor in the first-line treatment of a patient with advanced unresectable hepatocellular carci-noma. The results show that partial response being achieved according to the modified response evaluation criteria in solid tumors, and the survival time is more than 20 months with no obvious adverse reactions and high quality of life.

Acquired blood coagulation factor Ⅴ deficiency in a patient with severe burn / 中华烧伤杂志

In March 2017, a severely burned male patient aged 36 years with hypovolemic shock was admitted to our hospital. The patient received large quantities of antibiotics and blood products and repeated skin graft after admission, and then he suffered wound errhysis and throat congestion. The patient was healthy before without family history of bleeding or thrombosis disease. Laboratory tests showed that prothrombin time and activated partial coagulation time were remarkably prolonged, blood coagulation factor Ⅴ activity was extremely low, and the result of qualitative test of coagulation factor inhibitor was positive. Acquired blood coagulation factor Ⅴ deficiency was diagnosed. After application of dexamethasone (5 mg, twice per day) and infusion of fresh frozen plasma, blood coagulation indicators of patients recovered in 4 days, the result of qualitative test of coagulation factor inhibitor was negative, and bleeding symptoms were improved.

Predictive Value of Serum Interleukin-1β and Interleukin-6 Levels for Clinical Response to Etanercept Treatment in Patients with Rheumatoid Arthritis / 中国医科大学学报

Objective To investigate the predictive value of eight pro-inflammatory protein levels in serum for clinical response to etanercept (ETN) treatment in patients with rheumatoid arthritis (RA). Methods This study enrolled 58 consecutive patients with active RA. All patients received ETN for 24 weeks "on demand" based on clinical need and patient request. Serum samples were obtained from each patient at baseline and biomarker levels were quantified with enzyme-linked immunosorbent assay. Results After 24 weeks, 38 RA patients who achieved a clinical response were categorized as the responder group, while 20 RA patients who failed to achieve clinical response were included in the non-responder group. Baseline serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were increased in the responder group compared to those in the non-responder group (P = 0.011 and P = 0.004, respectively). Receiver operating characteristic curves showed that both baseline serum IL-1β (AUC:0.703, 95％ CI:0.558-0.847) and IL-6 (AUC:0.732, 95％ CI:0.601-0.862) expression had a good predictive value in distinguishing responders from non-responders. In addition, univariate and multivariate logistic regression analysis showed that high expression of IL-6 was an independent predictor of clinical response to ETN treatment (P = 0.031).Conclusion Baseline IL-1β and IL-6 expression might be useful as biomarkers for predicting clinical response to ETN treatment in RA patients.

Isoniazid treatment for latent tuberculosis infection is tolerable for rheumatoid arthritis patients receiving tumor necrosis factor inhibitor therapy

BACKGROUND/AIMS: To evaluate the impact of isoniazid (INH) treatment for latent tuberculosis infection (LTBI) on the development of liver function test (LFT) abnormality and the persistence of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. METHODS: We retrospectively enrolled patients with RA who were treated with TNF inhibitors at a university hospital between December 2000 and November 2011. After dividing the patients into two groups based on the occurrence of LFT abnormality during follow-up, we compared demographic and clinical features between the two groups. A multivariable logistic regression analysis was performed to identify the impact of INH treatment on LFT abnormality. The impact of INH treatment on the persistence of TNF inhibitors was also evaluated with the log-rank test and the Cox-proportional hazards model. RESULTS: A total of 312 RA patients including 96 patients (30.9%) who took INH for LTBI were included in this analysis. Thirty-nine patients (12.5%) experienced LFT abnormalities while using TNF inhibitors. The use of INH was associated with LFT abnormalities (odds ratio, 3.01; 95% confidence interval [CI], 1.39 to 6.48) after adjusting for covariates, including methotrexate use. However, the persistence of TNF inhibitors over 5 years did not differ between patients receiving or not receiving INH treatment (49.4 vs. 54.6%, p = 0.79). INH treatment was not a risk factor for discontinuation of TNF inhibitors (hazard ratio, 1.01; 95% CI, 0.66 to 1.57). CONCLUSION: INH treatment for LTBI in RA patients who started TNF inhibitors is associated with the occurrence of LFT abnormality; however, it does not lead to discontinuation of TNF inhibitors.

Rapid onset of efficacy predicts response to therapy with certolizumab plus methotrexate in patients with active rheumatoid arthritis

BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSIONS: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

Correlation of Serum Calprotectin Expression with Clinical Response in Juvenile Idiopathic Arthritis Patients Treated with a Tumor Necrosis Factor Inhibitor / 中国医科大学学报

Objective To investigate the correlation of serum calprotectin (MRP8/14) expression with clinical response in Chinese juvenile idiopathic arthritis (JIA) patients treated with a tumor necrosis factor (TNF) inhibitor.Methods Seventy-two JIA patients and 30 health volunteers (HCs) were enrolled in this prospective study.All JIA patients received etanercept for 24 weeks.Serum was collected from JIA patients at baseline before treatment and from HCs.Clinical response was defined according to the American College of Rheumatology (ACR) Pedi 50 criteria.Results Serum MRP8/14 expression was greater in JIA patients than in HCs (P ＜ 0.001).Serum MRP8/14 level was greater in responders than in non-responders (area under the receiver operating characteristic curve,0.823;95％ CI:0.706-0.939).Univariate and multivariate logistic analysis showed that high serum MRP8/14 expression was an independent predictive factor for clinical response (P =0.003).Conclusion Serum MRP8/14 level can be used as a convincing and novel biomarker for clinical response in JIA patients treated with a TNF inhibitor.

Meta-analysis of the Efficacy and Safety of Anti-vascular Endothelial Growth Factor Inhibitor in the Treat-ment of Retinopathy of Prematurity / 中国药房

OBJECTIVE:To systematically review the efficacy and safety of anti-vascular endothelial growth factor(VEGF)in-hibitors in the treatment of retinopathy of prematurity (ROP),and provide evidence-based reference for clinic. METHODS:Re-trieved from PubMed,EMBase,Cochrane Library,CJFD,VIP,CBM and Wangfang Database,randomized controlled trials (RCT) about VEGF inhibitors (test group) versus laser photocoagulation treatment (control group) in the treatment of ROP were collected. Meta-analysis was performed by using Rev Man 5.1 software after data extraction and quality evaluation by Cochrane re-viewers manual 5.1.0. RESULTS:Totally 5 RCTs were included,involving 381 infants and 754 eyes.Results of Meta-analysis showed that the recurrence rate of ROP [RR=0.23,95%CI(0.13,0.42),P0.05). CONCLUSIONS:Intravitreal VEGF inhibitors have better efficacy than laser photocoagulation in the treatment of ROP,but the optimal dose and safety need further verification by large-sam-ple and well-designed RCT.

Incidence of Tuberculosis in Rheumatoid Arthritis Patients Using Anti-Tumor Necrosis Factor Agents following Latent Tuberculosis Infection Screening Strategies

OBJECTIVE: To compare the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients using tumor necrosis factor (TNF) inhibitors following two strategies for latent tuberculosis infection (LTBI) screening: Tuberculin skin test (TST) only vs. TST plus Qauntiferron-TB gold in tube (QFT-GIT). METHODS: Data was extracted from a retrospective cohort of Korean RA patients who used biologic agents. Of the 406 RA patients who underwent TST before starting TNF inhibitor, we selected 355 patients who strictly followed LTBI screening and treatment strategies. Two hundred and twenty-two patients were classified as TST only group and the remaining 133 patients as TST plus QFT-GIT group. We calculated the standardized incidence ratio of TB in the entire sample and compared the TB incidence between groups. RESULTS: Among the patients who received the TST only strategy (n=222, 538.6 person-year [PY]), two patients developed TB during anti-TNF therapy, while of those who followed the TST plus QFT-GIT strategy, none developed TB (n=133, 108.8 PY). The overall crude incidence of TB in RA patients using TNF inhibitors was 314 per 100,000 PY. Compared with the general population, the overall age standardized incidence of TB in TNF inhibitor users who followed management guideline for LTBI was 3.9. CONCLUSION: Despite following screening and management guidelines for LTBI, TB incidence for RA patients during anti-TNF therapy is higher than in the general population. Combining QFT-GIT with TST as a screening for LTBI might be reduce the risk of TB.

Pulmonary Cryptococcosis in a Patient with Ankylosing Spondylitis treated with Etanercept

Ankylosing spondylitis (AS) is a chronic inflammatory disorder, commonly characterized by inflammation of axial skeleton and development of enthesopathies. Tumor necrosis factor inhibitors (TNFi) shows good therapeutic responses in AS patients without good response to non-steroidal anti-inflammatory drugs. Although TNFi are relatively safe for AS patients, serious opportunistic infections, including tuberculosis and fungal infection, could develop. Here, according to our knowledge, we report a first Korean case of pulmonary cryptococcosis in a patient with AS treated with etanercept. A 64 year-old man with AS visited due to a newly appeared pulmonary nodule on a routine chest radiography. He had been administered etanercept for 5 months. Histologic findings of the lung nodule showed characteristic features of cryptococcosis. Etanercept was discontinued and oral fluconazole was administrated, as there was no evidence of central nervous system involvement. After 7 months of treatment, chest CT showed an improvement of the pulmonary lesion.

The therapeutic effect of etanercept on intractable ankylosing apondylitis related hip joint diseases / 中华风湿病学杂志

Objective To observe the therapeutic effect of tumor necrosis factor inhibitor (Etanercept) on intractable ankylosing spondylitis (AS) related hip joint lesion. Methods Thirty-five patients with AS with unilateral or bilateral hip joints pain and limitation of joint motion were included into this study. The patients' conditions were not controlled under standard treatment by non-steroidal anti-inflamma-tory drug and antirheumatic medications. The clinical trial was designed as a prospectiveopen study, 35 pati-ents received Etanercept 50 mg once a week for 12 weeks, combined with methotrexate (MTX) 10 mg once a week. Parameters including Harris hip score, Bath ankylosing spondylitis radiologic index-hip (BASRI-hip), Bath ankyiosing spondylitis disc.use activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were evaluated and side effects were observed before and after the treatment. Results Fifty-five hip joints were involved in 35 patients, in which unilateral hip involvement in 15 patients and bilateral in 20 patients. Harris score of the hips iner-eased significantly from 51±4 before treatment to 86±5 (P=0.000) after treatment ; Before and after treatment, BASDAI changed from 6.4±1.2 to 4.4±0.8 (P=0.000), BASFI was changed from 6.3±1.1 to 3.4±0.8 (P=0.000), before and after treatment ESR was changed from (68±28) mm/l h to (25±6) mm/l h (P=0.001), CRP changed from (59.1±22.3) mg/l, to (6.9±1.1) mg/L (P=0.000) before and after treatment respectively, but BASRI-hip was not changed obviously before and after treatment. No tuberculosis and serious side effects was observed during the treatment and follow-up period. Conclusion Etanercept, when combined with methotrexate, could be used to treatintractahle AS-related hip joint lesions. This regimen could improve the hip joint function and control the disease activity without serious side effects.

Etanercept combined with methotrexate in the induction and maintenance therapy of hip joint lesion of ankylosing spondylitis / 中华风湿病学杂志

Objective To explore the efficacy of tumor necrosis factor inhibitor in hip joint lesion of ankylosing spondylids (AS). Methods Eight-six patients with hip joint lesion of ankylosing spondylitis were Enrolled in this study. The treatment protocol was: ①Etanercept 25 mg was suncutaneously injected twice a week in the first two months and once a week in the following two months. Then it was injected once every oth-er two weeks in the last two months of the study period.②Methotrexate 15 mg was administered orally or in-travenously once a week.③NSAIDs and prednisone were stopped when symptoms sunsides. Results Twenty-eight cases (33%) stopped NSAIDs because of the disappearance of symptoms in 2 weeks after starting of the study. Forty-three (50%) stopped NSAIDs with in 8 weeks and 36 cases (42%) in them stopped NSAIDs and prednisone. During the 9th and 16th week, etanercept was used once a week and 49 cases (60%) stopped NSAIDs and prednisone. During the 17th and 24th week, etanercept was used once every two weeks, and 38 cases (44%) stopped NSAIDs and prednisone and their disease was stable. Hip Functional Scores of patients were elevated significantly at 2, 4 and 6 months after the treatment (p<0.05) BASDAI and BASFI decreased, and the difference was significant when compared to those before the treatment (P<0.05). For the 19 cases with hip joint synovitis and hydrarthrosis in MRI image but without obvious change in pelvic plain films, syn-ovitis of 11 cases disappeared and 4 cases improved significantly. In 84 hip joints with grade Ⅱ or Ⅲ changes, 13 joints improved for one grade, 16 joints had improvement but less than one grade, and 49 joints had no radiological changes. Conclusion Etanercept, when combined with methotrexate, is effective in treat-ing hip joint lesion of ankylosing spondylitis. The dosage of etanercept can be tapered after the disease is un-der control.