AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNF...AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.展开更多
AIM To investigate the correlation between rs2910164,rs11614913,rs113054794,and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD).METHODS One hundred seven patients ...AIM To investigate the correlation between rs2910164,rs11614913,rs113054794,and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD).METHODS One hundred seven patients with CD based on standardclinical,endoscopic,radiological,and pathological criteria were included in the study.They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines.Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively.Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and nonresponders.Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study.Seventy two(67.3%)patients were classified as complete responders,22(20.5%)as partial while 13(12.1%)were primary non-responders.No correlation was detected between response to anti-TNF agents and patients'characteristics such as gender,age and disease duration while clinical and biochemical indexes used were associated with endoscopic response.Concerning prevalence of rs2910164,rs11614913,and rs188519172 polymorphisms of miR-146,miR-196a and miR-224 respectively no statistically important difference was found between complete,partial,and non-responders to antiTNF treatment.Actually CC genotype of rs2910164 was not detected in any patient.Regarding rs113054794 of miR-221,normal CC genotype was the only one detected in all studied patients,suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients'response to anti-TNF treatment.Polymorphism rs113054794 is not detected in our population.展开更多
Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive pati...Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive patients diagnosed with RA (ACR 1987 criteria) (DAS 28 2.6) were included, being treated with anti-tumor necrosis factor inhibitors (anti-TNF) (cases) and non-biological disease-modifying anti-rheumatic drugs (DMARD) (controls), without risk factors for insulin resistance (administration of steroids, body mass index > 25 kg/m2, diabetes mellitus or use of glucose lowering agents, systemic arterial hypertension or use of anti-hypertensive drugs, triglycerides > 150 mg/dl, hypercholesterolemia > 200 mg/dl, high-density lipoproteins 40 mg/dl in men and 50 mg/in women, or with lipids lowering agents, waist measurement > 88 cm in women and > 102 cm in men). We used HOMA (Homeostasis Model Assessment) to determine insulin resistance in both groups, HOMA being defined as >1 and sensitivity to insulin using QUICKI (Insulin Sensitivity Check Index), ≥0.38 being considered as normal. The Mann Whitney U was used for the statistical analysis. Results: A total of 28 patients, 15 being treated with non-biological DMARDs and 13 with anti-TNF therapy, were evaluated;89.7%, of which were women. Average age: 43.5 (range 21 - 62);the average HOMA index of the non-biological DMARD group was 1.58 (range 0.7 - 5.4), compared with patients treated with anti-TNF therapy, 1.18 (range 0.2 - 4.3) (P = 0.5). The average QUICKI index was 0.36 (range 0.30 - 0.42) in patients treated with non-biological DMARD, compared with0.37 inpatients treated with anti-TNF therapy (range 0.30 - 0.51) (P = 0.8). Conclusion: Resistance to insulin manifested itself in both groups, although there was a greater trend of less insulin resistance and greater sensitivity in the anti-TNF group;this was probably not statistically significant due to the sample size.展开更多
AIM:To investigate effects of anti-TNF biologic drugs on uveitis severity(comparing visual acuity log MAR levels) in Behcet patients.METHODS:Three databases Pub Med, Scopus, and the Web of Science were searched for qu...AIM:To investigate effects of anti-TNF biologic drugs on uveitis severity(comparing visual acuity log MAR levels) in Behcet patients.METHODS:Three databases Pub Med, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behcet’s disease(BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted. RESULTS:The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis(with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies(28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity log MAR levels(MD=-1.5 IU/L, 95%CI:-2.1,-0.01).CONCLUSION:Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values.展开更多
The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scal...The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.展开更多
In patients with severe psoriasis that at the same time have multiple comorbidities and chronic infections, is difficult to establish safer and more effective therapy. There are contradictions between the indications ...In patients with severe psoriasis that at the same time have multiple comorbidities and chronic infections, is difficult to establish safer and more effective therapy. There are contradictions between the indications of the international protocols of systemic treatments, and the most recent publications which show that anti-TNFα agents could be safe therapeutic options in patients with chronic hepatitis. In the case of chronic viral infections, specifically hepatitis B, there are several conflicts in reference to the biological treatments that can block tumoral necrosis factor-α (TNFα) because there is evidence of a risk of reactivation of hepatitis. Most viral reactivations with the administration of an anti-TNFα agent have been reported in patients with inflammatory diseases. However, there are a few cases described in psoriasis. We’ll present the first case reported in literature of hepatisis B viral (HBV) reactivation in a patient with severe psoriasis secondary to the administration of adalimumab.展开更多
There have been several reports of tuberculosis (TB) and, less frequently, of nontuberculous mycobacterial (NTM) infections in association with tumor necrosis factor α inhibitor (anti-TNFα) therapy. Mycobacterium ma...There have been several reports of tuberculosis (TB) and, less frequently, of nontuberculous mycobacterial (NTM) infections in association with tumor necrosis factor α inhibitor (anti-TNFα) therapy. Mycobacterium marinum is a NTM with a distinct epidemiology and is infrequently responsible for disease in humans. Most commonly, it causes localized skin infections, but in 20% to 40% of cases, it involves deeper structures. Disseminated disease is exceptional and has been reported to occur only in immunocompromised patients. The authors report a clinical case of tenosynovitis and sporotrichoid disease due to M. marinum in a 45-year-old male patient under anti-TNFα therapies for spondyloarthropathy. Along antimicrobial therapy, the patient underwent surgical debridement and after two years he is still on treatment but substantially improved. A few cases of M. marinum infection occurring in patients treated with anti-TNFα drugs have been reported. The diagnosis of infection due to M. marinum requires a high index of suspicion from a properly obtained exposure history and is important so that efficient diagnostic approach and treatment are ensured.展开更多
Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is a...Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is an indirect measure of the efficacy, safety, and tolerability of a drug. The objective of the study was to analyze the drug survival rate of biological therapy in a national health system (SUS). Methods: A retrospective cohort study of the medication process of RA was carried out in public pharmacies of a Brazilian state from January 2010 to April 2017. The Kaplan-Meier survival analysis was applied. The survival rate was defined as the incidence of drug discontinuation. The retention rate was defined as the mean of months using the drug. Results: Of the total of 902 individuals, 83.6% were female with a mean age of 56 years. Anti-TNF, mostly adalimumab (ADA), was the main biological agent prescribed. Mean drug retention of the first biological was 59.6 months (95% CI: 56.7 - 62.5), followed by 53.7 (95% CI: 48 - 59.4) and 28.2 (95% CI: 23.1 - 23.3) months for the second and third biologicals, respectively. Among the anti-TNF group, ADA, ETN, IFX had the better retention rate. There was no statistical difference in the general survival analyses (p = 0.18) among the groups. However, along the first 2 years, ADA, ETN, and RTX had the three better drug survival. The drug retention seems to increase with age (p = 0.036), with the subgroups > 70 years of age having the highest means (70 - 80 years: 67.29;>80: 67.53). Among all, 27.1% of patients switched to a second biologic. Conclusion: The anti-TNF group, mostly adalimumab (ADA), is the most prescribed medication as first and second-line therapy, reflecting its accessibility in the SUS and efficiency of the follow-up protocols. Among the anti-TNF group, ADA, ETN, and IFX had the better retention rate. Additionally, ADA and ETN had the better drug survival for the first treatment in the first 2 years. RTX was the non-anti-TNF with the best survival. A quarter of patients who start a biological therapy fail and switch to another drug (27%).展开更多
文摘AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.
文摘AIM To investigate the correlation between rs2910164,rs11614913,rs113054794,and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD).METHODS One hundred seven patients with CD based on standardclinical,endoscopic,radiological,and pathological criteria were included in the study.They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines.Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively.Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and nonresponders.Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study.Seventy two(67.3%)patients were classified as complete responders,22(20.5%)as partial while 13(12.1%)were primary non-responders.No correlation was detected between response to anti-TNF agents and patients'characteristics such as gender,age and disease duration while clinical and biochemical indexes used were associated with endoscopic response.Concerning prevalence of rs2910164,rs11614913,and rs188519172 polymorphisms of miR-146,miR-196a and miR-224 respectively no statistically important difference was found between complete,partial,and non-responders to antiTNF treatment.Actually CC genotype of rs2910164 was not detected in any patient.Regarding rs113054794 of miR-221,normal CC genotype was the only one detected in all studied patients,suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients'response to anti-TNF treatment.Polymorphism rs113054794 is not detected in our population.
文摘Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive patients diagnosed with RA (ACR 1987 criteria) (DAS 28 2.6) were included, being treated with anti-tumor necrosis factor inhibitors (anti-TNF) (cases) and non-biological disease-modifying anti-rheumatic drugs (DMARD) (controls), without risk factors for insulin resistance (administration of steroids, body mass index > 25 kg/m2, diabetes mellitus or use of glucose lowering agents, systemic arterial hypertension or use of anti-hypertensive drugs, triglycerides > 150 mg/dl, hypercholesterolemia > 200 mg/dl, high-density lipoproteins 40 mg/dl in men and 50 mg/in women, or with lipids lowering agents, waist measurement > 88 cm in women and > 102 cm in men). We used HOMA (Homeostasis Model Assessment) to determine insulin resistance in both groups, HOMA being defined as >1 and sensitivity to insulin using QUICKI (Insulin Sensitivity Check Index), ≥0.38 being considered as normal. The Mann Whitney U was used for the statistical analysis. Results: A total of 28 patients, 15 being treated with non-biological DMARDs and 13 with anti-TNF therapy, were evaluated;89.7%, of which were women. Average age: 43.5 (range 21 - 62);the average HOMA index of the non-biological DMARD group was 1.58 (range 0.7 - 5.4), compared with patients treated with anti-TNF therapy, 1.18 (range 0.2 - 4.3) (P = 0.5). The average QUICKI index was 0.36 (range 0.30 - 0.42) in patients treated with non-biological DMARD, compared with0.37 inpatients treated with anti-TNF therapy (range 0.30 - 0.51) (P = 0.8). Conclusion: Resistance to insulin manifested itself in both groups, although there was a greater trend of less insulin resistance and greater sensitivity in the anti-TNF group;this was probably not statistically significant due to the sample size.
文摘AIM:To investigate effects of anti-TNF biologic drugs on uveitis severity(comparing visual acuity log MAR levels) in Behcet patients.METHODS:Three databases Pub Med, Scopus, and the Web of Science were searched for qualified papers focusing on the anti-TNF-α factors treatment in Behcet’s disease(BD)-associated uveitis. Studies that were designed pre and post anti-TNF drug treatment, were selected. After determining the search strategy for this study, the relevant data were extracted. RESULTS:The initial search was performed in the target databases and a total of about 1458 articles were found. Fifteen articles were selected for systematic review and only 12 of them had inclusion criteria for Meta-analysis(with visual acuity data). The mean dose of prednisolone before and after biological treatments was reported in 5 studies(28.56 and 7.56 mg/kg, respectively). Also, the preliminary results indicate a significant reduction in visual acuity log MAR levels(MD=-1.5 IU/L, 95%CI:-2.1,-0.01).CONCLUSION:Biological drugs significantly reduce the dose of prednisolone and affect visual acuity values.
文摘The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.
文摘In patients with severe psoriasis that at the same time have multiple comorbidities and chronic infections, is difficult to establish safer and more effective therapy. There are contradictions between the indications of the international protocols of systemic treatments, and the most recent publications which show that anti-TNFα agents could be safe therapeutic options in patients with chronic hepatitis. In the case of chronic viral infections, specifically hepatitis B, there are several conflicts in reference to the biological treatments that can block tumoral necrosis factor-α (TNFα) because there is evidence of a risk of reactivation of hepatitis. Most viral reactivations with the administration of an anti-TNFα agent have been reported in patients with inflammatory diseases. However, there are a few cases described in psoriasis. We’ll present the first case reported in literature of hepatisis B viral (HBV) reactivation in a patient with severe psoriasis secondary to the administration of adalimumab.
文摘There have been several reports of tuberculosis (TB) and, less frequently, of nontuberculous mycobacterial (NTM) infections in association with tumor necrosis factor α inhibitor (anti-TNFα) therapy. Mycobacterium marinum is a NTM with a distinct epidemiology and is infrequently responsible for disease in humans. Most commonly, it causes localized skin infections, but in 20% to 40% of cases, it involves deeper structures. Disseminated disease is exceptional and has been reported to occur only in immunocompromised patients. The authors report a clinical case of tenosynovitis and sporotrichoid disease due to M. marinum in a 45-year-old male patient under anti-TNFα therapies for spondyloarthropathy. Along antimicrobial therapy, the patient underwent surgical debridement and after two years he is still on treatment but substantially improved. A few cases of M. marinum infection occurring in patients treated with anti-TNFα drugs have been reported. The diagnosis of infection due to M. marinum requires a high index of suspicion from a properly obtained exposure history and is important so that efficient diagnostic approach and treatment are ensured.
文摘Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is an indirect measure of the efficacy, safety, and tolerability of a drug. The objective of the study was to analyze the drug survival rate of biological therapy in a national health system (SUS). Methods: A retrospective cohort study of the medication process of RA was carried out in public pharmacies of a Brazilian state from January 2010 to April 2017. The Kaplan-Meier survival analysis was applied. The survival rate was defined as the incidence of drug discontinuation. The retention rate was defined as the mean of months using the drug. Results: Of the total of 902 individuals, 83.6% were female with a mean age of 56 years. Anti-TNF, mostly adalimumab (ADA), was the main biological agent prescribed. Mean drug retention of the first biological was 59.6 months (95% CI: 56.7 - 62.5), followed by 53.7 (95% CI: 48 - 59.4) and 28.2 (95% CI: 23.1 - 23.3) months for the second and third biologicals, respectively. Among the anti-TNF group, ADA, ETN, IFX had the better retention rate. There was no statistical difference in the general survival analyses (p = 0.18) among the groups. However, along the first 2 years, ADA, ETN, and RTX had the three better drug survival. The drug retention seems to increase with age (p = 0.036), with the subgroups > 70 years of age having the highest means (70 - 80 years: 67.29;>80: 67.53). Among all, 27.1% of patients switched to a second biologic. Conclusion: The anti-TNF group, mostly adalimumab (ADA), is the most prescribed medication as first and second-line therapy, reflecting its accessibility in the SUS and efficiency of the follow-up protocols. Among the anti-TNF group, ADA, ETN, and IFX had the better retention rate. Additionally, ADA and ETN had the better drug survival for the first treatment in the first 2 years. RTX was the non-anti-TNF with the best survival. A quarter of patients who start a biological therapy fail and switch to another drug (27%).
