Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents

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.

Association of miR-146 rs2910164,miR-196a rs11614913,miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease

AIM To investigate the correlation between rs2910164, rs11 614913, 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.

Effect of Anti-TNF Therapy on Resistance to Insulin in Patients with Rheumatoid Arthritis

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.

Effects of anti-TNF biologic drugs on uveitis severity in Behcet patients: systematic review and Meta-analysis

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.

Tenosynovitis and Sporotrichoid Disease Due to <i>M. marinum</i>on a Patient under Anti-TNF<i>α</i>Therapy

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.

Gastric Neoplasia during Anti-TNF Therapy for Crohn’s Disease: Casual Event?

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.

Reactivation of Hepatitis B after Administration of Anti-TNF<i>α</i>in a Patient with Psoriasis

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.

Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Hepatitis B virus(HBV) reactivation in rheumatoid arthritis(RA) patients undergoing biological therapy is not infrequent. This condition can occur in patients with chronic hepatitis B as well as in patients with resolved HBV infection. Current recommendations are mainlyfocused on prevention and management strategies of viral reactivation under tumor necrosis factor-α inhibitors or chimeric monoclonal antibody rituximab. In recent years, growing data concerning HBV reactivation in RA patients treated with newer biological drugs like tocilizumab and abatacept have cumulated. In this review, epidemiology, pathogenesis and natural history of HBV infection have been revised first, mainly focusing on the role that specific therapeutic targets of current biotechnological drugs play in HBV pathobiology; finally we have summarized current evidences from scientific literature, including either observational studies and case reports as well, concerning HBV reactivation under different classes of biological drugs in RA patients. Taking all these evidences into account, some practical guidelines for screening, vaccination, prophylaxis and treatment of HBV reactivation have been proposed.

Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: An open-label study

AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.

A 10-Year Saudi Experience of Using Adalimumab in Treating Juvenile Idiopathic Arthritis

Background: Traditionally, management of Juvenile Idiopathic Arthritis (JIA) involves use of non-steroidal anti-inflammatory drugs (NSAIDS) or disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or sulfasalazine;or steroids. However, in several cases, a low therapeutic response or important side effects is encountered. This study reports our experience in using adalimumab in JIA patients by assessing the efficacy and safety of this treatment in this category of patients. Methods: A retrospective study was conducted among 38 patients with JIA at the Pediatric Department, King Abdulaziz Univesrity Hospital, Jeddah, Saudi Arabia, in the period January 2005-March 2016. Patients’ records were reviewed and relevant demographic and clinical data were collected. Data were analyzed using SPSS version 21 and represented using tables. Results: The 38 patients were distributed as 11 (28.9%) males and 27 (71.1%) females;mean ± SD age was 11.91 ± 4.54 (range = 3 - 19) years. Mean ± SD (range) disease duration was 3.26 ± 2.52 (0 - 12) years and most frequent diagnoses included polyarticular rheumatoid factor (RF) negative form 12 (31.6%), followed by systemic and oligoarticular JIA with 9 (23.7%) cases each. Before adalimumab, fever was present in 13 (34.2%) cases, followed by rash in 8 (21.0%) cases;while 21 (55.3%) were asymptomatic. Thirty-one (81.6%) were in failure of MTX, 19 (50%) of steroids, 7 (18.4%) of NSAIDS and 3 (7.9%) had had intraarticular injections. Biologically, ANA, RF and anti-CCP were positive in 22 (57.9%), 8 (21.1%) and 4 (10.5%) of the cases, respectively. Uveitis was present in 11 (28.9%) of the patients. Analysis of adalimumab efficacy showed 10 (52.6%) cases of complete remission, 9 (23.7%) of partial remission and 9 (23.7%) other where treatment was discontinued. Major adverse effects included local pain (4 [10.5%]), new onset uveitis (1 [2.6%]) and rash (1 [2.6%]), responsible of 1case of treatment discontinuation. Predictors for complete remission on adalimumab were oligoarticular form (β = 3.450, p = 0.009) and negative RF (β = 2.381, p = 0.036);while predictors for nonresponse, whether complete or partial, were polyarticular form (β = ?3.784, p = 0.005) and positive anti-CCP (β = ?3.178, p = 0.021). Conclusion: Adalimumab is an efficient and relatively safe alternative in the treatment of JIA with relatively high remission rates and lower rates of adverse effects. Further multicentre experiences are warranted to prove its efficacy and safety in the Saudi patients.

Biopharmaceuticals for prevention of COVID-19:A scoping review

The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.

Inflammatory bowel disease in liver transplanted patients

Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.

Henoch-Schnlein purpura complicating adalimumab therapy for Crohn's disease

Anti-tumour necrosis factor-α(TNF) therapy has revolutionised the management of chronic inflammatory conditions.With ever increasing numbers of patients being treated with these agents,uncommon adverse reactions will inevitably occur more frequently.Cutaneous manifestations are associated with many of these chronic conditions and can complicate anti-TNF therapy in about 20% of cases.Vasculitic complications are rarely associated with anti-TNF therapy.Henoch-Schnlein purpura(HSP),a small vessel vasculitis,has been described following infliximab and etanercept therapy but never with adalimumab,a fully humanized TNF antibody.The risk of such immune-mediated reactions is theoretically less with adalimumab compared to infliximab but can still occur.Here we report the f irst case in the literature of HSP that can be attributed to the use of adalimumab in a 19-year-old male with recalcitrant Crohn's disease.

TNF-<i>α</i>Antagonist and Infection in Rheumatoid Arthritis

Background: Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding. Methods: 383 anti-TNF-na?ve RA patients on ≥ 1 non-biologic-DMARD at enrollment from the Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW). Results: Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RRmvar_adj = 2.1, 95% CI: 0.8 - 5.8). Conclusions: Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.

Antibodies to Tumor Necrosis Factors in the Treatment of Rheumatoid Arthritis and Spondyloarthritis: The Basic Science, Clinical Science and Unmet Needs;Results from a Single Center

Inflammatory rheumatological diseases like rheumatoid arthritis (RA) and ankylosing spondylitis/Spondyloarthritis (AS/SpA), have been treated with NSAIDs (non steroidal anti-inflammatory drugs), corticosteroids, and DMARDs (disease modifying anti-rheumatic drugs).These have been only partially effective for the management of symptoms, since they are rarely associated with the complete control of disease and rarely slow down radiological damage. Several cytokines have been implicated in the pathogenesis of the inflammation and tumor necrosis factor (TNF) is the most important. The last decade and a half has seen advances in the form of “anti-TNF” therapies for RA and AS/SpA patients which target and neutralize the TNF cytokines, and thus reduce the disease activity. Two anti-TNF therapies have been used in India for treating DMARD resistant RA and AS/SpA for the last 13 years;Infliximab and Etanercept respectively. This paper is a description of the clinical outcomes and unmet needs/toxicities associated with the treatment of RA and AS/SpA with anti-TNF therapies (Infliximab, Etanercept), at a single rheumatology center (tertiary care, super-specialty hospital, Indraprastha Apollo Hospitals, New Delhi) in north India.

重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体在类风湿关节炎患者体内药动学研究

目的:研究连续静脉滴注重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体(anti-TNF rcMAb)在类风湿关节炎患者体内的药动学。方法:按GCP指导原则设计试验方案,选择9例类风湿关节炎患者,年龄(41±16)岁,在2h内匀速静脉滴注anti-TNF rcMAb,每次3mg·kg-1,共给药5次,用酶联免疫吸附法(ELISA)测定人血清中各点anti-TNF rcMAb浓度。采用DAS2.1.1软件进行数据处理,计算药动学参数。结果:受试者多次静脉滴注anti-TNF rcMAb,按非房室模型计算,主要药动学参数t1/2为(9.2±1.8)d,Cssmax为(0.008±0.001)mg·L-1,Tssmax为(0.092±0.018)d,AUCss为(248±38)mg.d.L-1,Vss为(0.10±0.08)L·kg-1,DF为(5.5±0.6)。受试者在给药期间未出现严重不良反应。结论:本研究在给药后第3次时血药浓度可达到稳态,连续给药5次后体内未见蓄积,该方案适宜在临床推广使用。建议临床按此方案用药时,使用时间不宜过长,以减少药物不良反应。

重组抗肿瘤坏死因子-α人鼠嵌合单克隆抗体对类风湿关节炎患者的疗效及其Th细胞亚群的影响

目的研究重组抗肿瘤坏死因子-α（TNF-α）人鼠嵌合单克隆抗体（anti—TNF rcMAb）对类风湿关节炎（RA）患者治疗效果及对患者外周血Th1、Th17、调节性T细胞影响。方法50例经严格筛选的RA患者按随机分配原则分为2组。联合治疗组（40例），给予anti-TNF rcMAb（3mg／kg）＋甲氨蝶呤治疗；对照组（10例）单独接受甲氨蝶呤治疗，分别于0、2、6、14周给药，于0、18周分别观察联合治疗组与对照组的相关临床指标的变化，在相应观察点做ACR20、50、70评分。同时，对比外周血中Th1、Th17、调节性T细胞的表达情况及相关转录因子T-bet、维甲酸相关孤核受体（ROR）C、叉头状转录因子3（Foxp3）的mRNA表达水平变化。采用t检验和χ^2检验或Ridit作统计学分析。结果治疗前后，联合治疗组ACR20、50、70较对照组均有所改善，尤其ACR20改善程度与对照组相比，差异有统计学意义（Z=1．671，P=0．00094）。联合治疗组患者外周血Th17细胞无显著变化[（0周（1．1±0．6）％；18周（1．1±0．3）％]、Th1细胞比例降低[0周（7．1±3．9）％；18周（4．2±2．8）％]，调节性T细胞比例明显升高[0周（91．5±0．8）％；18周（3．0±0．6）％，t=2．301，P=0．048]；对照组Th1比例下降[0周（9．1±3．1）％；18周（5．8±2．6）％]，调节性T细胞比例略升高[0周（1．2±0．6％）；18周（2．2±0．6）％]。2组Th17、Th1细胞的转录因子RORC、T-bet mRNA表达水平降低，调节性T细胞转录因子Foxp3的表达水平均升高。结论anti-TNF rcMAb联合甲氨蝶呤治疗对RA患者疗效显著，可能通过影响患者外周血Th细胞亚群发挥其治疗作用。

Biologics:how far can they go in Crohn’s disease?

Crohn’s disease is a chronic gastrointestinal inflammatory disorder,characterized by episodes of relapsing and remitting flares.As the disease mechanism becomes better elucidated,there is a significant increase in the number of available biologic therapies.This article summarizes and synthesizes current Food and Drug Administration-approved biological therapy for Crohn’s disease and examines the positioning of medical therapy as emerging biologics break onto the market.