anti-TNF Therapy In Crohn's Disease Research Articles

Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1β⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn’s disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn’s disease.

NOD2 in monocytes negatively regulates macrophage development through TNFalpha.

It is believed that intestinal recruitment of monocytes from Crohn's Disease (CD) patients who carry NOD2 risk alleles may repeatedly give rise to recruitment of pathogenic macrophages. We investigated an alternative possibility that NOD2 may rather inhibit their differentiation from intravasating monocytes. The monocyte fate decision was examined by using germ-free mice, mixed bone marrow chimeras and a culture system yielding macrophages and monocyte-derived dendritic cells (mo-DCs). We observed a decrease in the frequency of mo-DCs in the colon of Nod2-deficient mice, despite a similar abundance of monocytes. This decrease was independent of the changes in the gut microbiota and dysbiosis caused by Nod2 deficiency. Similarly, the pool of mo-DCs was poorly reconstituted in a Nod2-deficient mixed bone marrow (BM) chimera. The use of pharmacological inhibitors revealed that activation of NOD2 during monocyte-derived cell development, dominantly inhibits mTOR-mediated macrophage differentiation in a TNFα-dependent manner. These observations were supported by the identification of a TNFα-dependent response to muramyl dipeptide (MDP) that is specifically lost when CD14-expressing blood cells bear a frameshift mutation in NOD2. NOD2 negatively regulates a macrophage developmental program through a feed-forward loop that could be exploited for overcoming resistance to anti-TNF therapy in CD.

Correlation Among Body Composition Parameters and Long-Term Outcomes in Crohn's Disease After Anti-TNF Therapy.

BackgroundThe impact of the body composition on the pathophysiology and clinical course of Crohn's disease (CD) has not been fully elucidated.AimsTo reveal the correlations among body composition and long-term outcomes in CD after anti-TNF therapy.MethodsNinety-one patients who received anti-TNF therapy as their first biologic treatment were enrolled. The skeletal muscle index (SMI), visceral and subcutaneous fat area (VFA, SFA), and the ratio of the VFA to SFA (mesenteric fat index; MFI) at the 3rd lumbar level were measured using computed tomography (CT) imaging before the induction. The correlation among the body composition and outcomes were retrospectively analyzed.ResultsThe 5-year cumulative secondary failure- and resection-free rates in patients with a low SMI (39.1% and 64.8%) were significantly lower than those with a high SMI (67.5% and 92.7%; p = 0.0071 and 0.0022, respectively). The 5-year cumulative secondary failure-free rate in the patients with low VF (45.0%) was significantly lower than that in those with high VF (77.6%; p = 0.016), and the 5-year cumulative resection-free rate in patients with a high MFI (68.9%) was significantly lower than that in those with a low MFI (83.0%; p = 0.031). Additionally, patients with low age and BMI had significantly lower cumulative secondary failure- and resection-free rates than those with high age and BMI (low age: 37.4% and 71.2%; high age: 70.7% and 88.9%; p = 0.0083 and 0.027, respectively) (low BMI: 27.2% and 64.8%; high BMI: 68.3% and 87.9%; p = 0.014 and 0.030, respectively), respectively. In the multivariate analyses, a low SMI was the only independent risk factor for secondary failure (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.04–4.44), while low age (HR 4.06, 95% CI 1.07–15.4), a low SMI (HR 4.19, 95% CI 1.01–17.3) and high MFI were risk factors for bowel resection (HR 4.31, 95% CI 1.36–13.7).ConclusionThe skeletal muscle mass and ratio of visceral to subcutaneous fat were suggested to reflect the long-term clinical outcome and may be helpful as prognostic markers after anti-TNF therapy in CD.

Deep learning vs conventional learning algorithms for clinical prediction in Crohn's disease: A proof-of-concept study.

BACKGROUNDTraditional methods of developing predictive models in inflammatory bowel diseases (IBD) rely on using statistical regression approaches to deriving clinical scores such as the Crohn's disease (CD) activity index. However, traditional approaches are unable to take advantage of more complex data structures such as repeated measurements. Deep learning methods have the potential ability to automatically find and learn complex, hidden relationships between predictive markers and outcomes, but their application to clinical prediction in CD and IBD has not been explored previously.AIMTo determine and compare the utility of deep learning with conventional algorithms in predicting response to anti-tumor necrosis factor (anti-TNF) therapy in CD.METHODSThis was a retrospective single-center cohort study of all CD patients who commenced anti-TNF therapy (either adalimumab or infliximab) from January 1, 2010 to December 31, 2015. Remission was defined as a C-reactive protein (CRP) < 5 mg/L at 12 mo after anti-TNF commencement. Three supervised learning algorithms were compared: (1) A conventional statistical learning algorithm using multivariable logistic regression on baseline data only; (2) A deep learning algorithm using a feed-forward artificial neural network on baseline data only; and (3) A deep learning algorithm using a recurrent neural network on repeated data. Predictive performance was assessed using area under the receiver operator characteristic curve (AUC) after 10× repeated 5-fold cross-validation.RESULTSA total of 146 patients were included (median age 36 years, 48% male). Concomitant therapy at anti-TNF commencement included thiopurines (68%), methotrexate (18%), corticosteroids (44%) and aminosalicylates (33%). After 12 mo, 64% had CRP < 5 mg/L. The conventional learning algorithm selected the following baseline variables for the predictive model: Complex disease behavior, albumin, monocytes, lymphocytes, mean corpuscular hemoglobin concentration and gamma-glutamyl transferase, and had a cross-validated AUC of 0.659, 95% confidence interval (CI): 0.562-0.756. A feed-forward artificial neural network using only baseline data demonstrated an AUC of 0.710 (95%CI: 0.622-0.799; P = 0.25 vs conventional). A recurrent neural network using repeated biomarker measurements demonstrated significantly higher AUC compared to the conventional algorithm (0.754, 95%CI: 0.674-0.834; P = 0.036).CONCLUSIONDeep learning methods are feasible and have the potential for stronger predictive performance compared to conventional model building methods when applied to predicting remission after anti-TNF therapy in CD.

Systematic review: efficacy of escalated maintenance anti-tumour necrosis factor therapy in Crohn's disease.

Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). To perform a systematic review assessing the efficacy of escalated maintenance anti-TNF therapy in CD. EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full-text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included. A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%-100%) and remission (15%-83%) after empiric dose escalation for loss of response to standard anti-TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose-escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure-response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end-points. Strategies including Bayesian dashboard-dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long-term outcomes. Empiric escalation of maintenance anti-TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.

An Unexpected Cause of Headache and Splenic Lesions During Anti-TNF Therapy in Crohn Disease

An Unexpected Cause of Headache and Splenic Lesions During Anti-TNF Therapy in Crohn Disease

Association of TRAP1 with infliximab-induced mucosal healing in Crohn's disease.

Anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX), have been increasingly used to induce and maintain disease remission in patients with Crohn's disease (CD). Despite a considerable non-response rate, little is known about the genetic predictors of response to anti-TNF therapy in CD. Our aim in this study was to investigate the genetic factors associated with response to anti-TNF therapy in patients with CD. We performed a two-stage genome-wide association study (GWAS) to identify loci influencing the response to IFX among Korean patients with CD, comprising 42 good responders with mucosal healing and 70 non-responders. The achievement of mucosal healing was assessed by endoscopy and imaging. The functional significance of TRAP1 (TNF receptor associated protein 1) was examined using dextran sodium sulfate-induced colitis model in TRAP1 transgenic mice. The GWAS identified rs2158962, an intronic single nucleotide polymorphism (SNP) of TRAP1, significantly associated with mucosal healing (odds ratio=4.94; Pcombined =1.35×10-7 ). In the dextran sodium sulfate-induced acute colitis, TRAP1 transgenic mice showed a better response to IFX than the wild-type mice. The TRAP1 gene is associated with mucosal healing in CD patients following IFX therapy. Identifying the genetic predictors of mucosal healing to anti-TNF therapy can prevent patients from exposure to ineffective therapies.

Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared With Antitumor Necrosis Factor-α-Directed Therapy for Inflammatory Bowel Disease.

Objectives:Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD.Methods:A retrospective cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to 2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12-month period or new initiation of anti-TNF therapy, each treated as time-updating exposures. The primary outcome was all-cause mortality. Secondary outcomes included common causes of death. Marginal structural models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use relative to corticosteroids.Results:Among patients with CD, 7,694 entered the cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new anti-TNF users, respectively. The risk of death was statistically significantly lower in patients treated with anti-TNF therapy for CD (21.4 vs. 30.1 per 1,000 person-years, OR 0.78, 0.65–0.93) but not for UC (23.0 vs. 30.9 per 1,000 person-years, OR 0.87, 0.63–1.22). Among the CD cohort, anti-TNF therapy was also associated with lower rates of major adverse cardiovascular events (OR 0.68, 0.55–0.85) and hip fracture (OR 0.54, 0.34–0.83).Conclusions:Compared with prolonged corticosteroid exposure, anti-TNF drug use was associated with reduced mortality in patients with CD that may be explained by lower rates of major adverse cardiovascular events and hip fracture.

DOP030 Anti-TNF re-induction is as effective, simpler and cheaper compared with dose interval shortening following secondary loss of response in Crohn's disease: a dual centre “real world” study

Background: Anti-TNF re-induction (RI) refers to re-dosing infliximab (IFX, 5mg/kg) at weeks 0, 2, 6 or adalimumab (ADA, 160mg, 80mg) at weeks 0, 2, prior to resuming standard IFX (8-weekly) or ADA (2-weekly) dosing. RI presents a simple and cost effective alternative to ongoing dose interval shortening (DIS) to recapture response following secondary loss of response (2°LOR) to maintenance anti-TNF therapy. This study aimed to compare the “real world” cost and efficacy of anti-TNF RI and DIS following 2°LOR in Crohn's Disease (CD) and identify factors associated with durability of response. Methods: CD patients attending two Inflammatory Bowel Disease (IBD) centres in Melbourne, Australia between 1/1/2006–30/8/2016, who developed 2°LOR to maintenance anti-TNF and subsequently underwent RI or DIS, were retrospectively identified from existing IBD databases. DIS was standardised to 6-weekly IFX or weekly ADA. Treatment failure was defined as either CD-related bowel resection, discontinuation of, or switching to another biologic within 12 months of RI or DIS. “Real world” drug costs of RI and DIS were based on Australian Pharmaceutical Benefit Scheme pricing. Non-parametric statistics plus bi- and multivariate linear regression depicting variables associated with time to failure were calculated. Results: Of 423 patients on anti-TNF therapy for CD, 88 (21%) developed 2°LOR to IFX (51, 58%) and ADA (37, 42%) respectively. Median age and disease duration at 2°LOR was 36.6y (17.4–78.0) and 9.4y (0.7–35.2) respectively, with a median duration from anti-TNF initiation to 2°LOR of 2.1y (0.2–8.1). Baseline characteristics were similar between groups, except the RI group had more smokers (48% vs 18%, p<0.01). Subsequent RI or DIS was undertaken in 33 (38%) patients and 55 (62%) patients respectively. Treatment failure rates at 12 months were similar (27% vs 15%, p=0.17). Factors favourably associated with a durable response to either RI or DIS on multivariate linear regression included subtherapeutic serum anti-TNF levels (B 5.37 [4.82, 5.92]), initial RI (B 2.56 [2.24, 2.89]), use of IFX (B 1.52 [1.26, 1.78]), and concurrent, optimised thiopurines (B 0.68 [0.46, 0.91]), p<0.01). RI demonstrated lower median “real world” costs due to fewer anti-TNF doses during the follow-up period (median: AUD $4,839 vs $13,170, doses 2.0 vs 7.4, p<0.01). Figure 1. “Real world” comparison of additional anti-TNF drug costs associated with RI vs DIS. Conclusions: This “real world” study suggests that first-line RI following 2°LOR to anti-TNF therapy in CD was as effective, simpler and cheaper than first-line DIS. Larger prospective evaluation is now planned.

Genetic Markers Predict Primary Non-Response and Durable Response To Anti-TNF Biologic Therapies in Crohn's Disease.

One-fifth of patients with Crohn's disease (CD) are primary non-responders to anti-tumor necrosis factor (anti-TNF) therapy, and an estimated 10-15% will fail therapy annually. Little is known about the genetics of response to anti-TNF therapy. The aim of our study was to identify genetic factors associated with primary non-response (PNR) and loss of response to anti-TNFs in CD. From a prospective registry, we characterized the response of 427 CD patients to their first anti-TNF therapy. Patients were designated as achieving primary response, durable response, and non-durable response based on clinical, endoscopic, and radiologic criteria. Genotyping was performed on the Illumina Immunochip. Separate genetic scores based on presence of predictive genetic alleles were calculated for PNR and durable response and performance of clinical and genetics models were compared. From 359 patients, 36 were adjudged to have PNR (10%), 200 had durable response, and 74 had non-durable response. PNRs had longer disease duration and were more likely to be smokers. Fifteen risk alleles were associated with PNR. Patients with PNR had a significantly higher genetic risk score (GRS) (P =8 × 10-12). A combined clinical-genetic model more accurately predicted PNR when compared with a clinical only model (0.93 vs. 0.70, P <0.001). Sixteen distinct single nucleotide polymorphisms predicted durable response with a higher GRS (P =7 × 10-13). The GRSs for PNR and durable response were not mutually correlated, suggesting distinct mechanisms. Genetic risk alleles can predict primary non-response and durable response to anti-TNF therapy in CD.

Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab

BackgroundThe use of pharmacokinetics is associated with cost savings in anti-tumor necrosis factor (anti-TNF) therapy, but the long-term cost savings in a large cohort of Crohn's disease (CD) patients are unknown.AimThe goal of this study was to compare the cost of anti-TNF therapy in two cohorts of CD patients losing response to infliximab, one using a test-based strategy and one an empirical dose escalation.MethodsWe used a selected mathematical model to describe the trajectories of CD patients based on a discrete event system. This design allowed us to track over a given period a double cohort of patients who moved randomly and asynchronously from one state to another, while keeping all the information on their entire trajectory. Both cohorts were modeled using state diagram parameters where transition probabilities from one state to another are derived from literature data. Costs were estimated based on the French health care system.ResultsCost savings among the 10,000 CD patients using a test-based strategy were €131,300,293 at 5 years. At 5 years the mean cost saving was €13,130 per patient. The direct cost of the test had no impact on the results until the cost per test reached €2,000.ConclusionsA test-based strategy leads to major cost savings related to anti-TNF therapy in CD.

How fast up the ladder? Factors associated with immunosuppressive or anti-TNF therapies in IBD patients at early stages: results from a population-based cohort.

With the introduction of anti-TNF therapies in the treatment of IBD, the therapeutic strategies have changed to an accelerated step-up care to avoid long-term complications. Little is known about the implementation of these strategies into daily care. We aimed to evaluate this question and to identify factors associated with the early use of immunosuppressants or anti-TNF therapies in a population-based IBD cohort. Patients with an IBD diagnosed between January 2004 and December 2008 were included. Medical therapies were evaluated at first diagnosis and during a 5-year follow-up. Risk factors associated with the initiation of an immunosuppressive therapy were assessed. Two hundred and forty-one patients were evaluated (145 Crohn's disease (CD), 96 ulcerative colitis (UC)). An immunosuppressive or anti-TNF therapy was started in 83 CD (57.2 %) and 40 UC (43 %) patients (p = 0.033, relative risks (RR) 1.77; 95 % confidence interval (CI) 1.05-3.0). After 5 years, 38.8 % CD patients on immunosuppressive therapy were treated with anti-TNF therapies. The use of corticosteroids at first diagnosis, disease localization and surgery were independent predictors for an immunosuppressive or anti-TNF therapy in CD. In UC, the extension of disease was associated with immunosuppressive therapies. The use of steroids and localization in CD patients and an extended disease in UC patients affected the time until an immunosuppressive therapy was started. We found a high proportion of patients using an immunosuppressive therapy during the early course. Therefore, the accelerated step-up strategy seems to be successfully implemented in the daily care of IBD patients. We were able to identify several factors associated with an immunosuppressive or anti-TNF therapy in CD and UC.

A Sonographic Lesion Index for Crohn's Disease Helps Monitor Changes in Transmural Bowel Damage During Therapy

Therapeutic antibodies against tumor necrosis factor α (anti-TNF) are effective in patients with Crohn's disease (CD). Mucosal healing is a surrogate marker of efficacy, but little is known about the effects of anti-TNF agents on structural damage in the intestine. Small-intestine contrast ultrasonography (SICUS) is a valuable tool for assessing CD lesions. A new sonographic quantitative index (the sonographic lesion index for CD [SLIC]) was developed to quantify changes in CD lesions detected by SICUS. We explored whether the SLIC can be used to monitor transmural bowel damage in CD patients during anti-TNF therapy. We performed a prospective study of 29 patients with ileal or ileocolonic CD treated with anti-TNF agents; patients underwent SICUS before and after scheduled induction and maintenance therapy. To determine whether changes that can be detected by SICUS occur independently of anti-TNF therapy, 7 patients with ileal CD treated with mesalamine were enrolled as controls. A clinical response was defined as steroid-free remission, with CD activity index scores less than 150. We observed significant improvements in SLIC scores and subscores after induction and maintenance therapy with anti-TNFs, compared with before therapy. SLIC scores and subscores and index classes were improved significantly in patients with vs without clinical responses. Controls had no improvements in terms of CD activity index or SLIC scores, or index classes. Sonographic assessment using the quantitative index SLIC can be used to monitor changes in transmural bowel damage during anti-TNF therapy for CD.

Expression of IL-2, IL-17 and TNF-alpha in patients with Crohn's disease treated with anti-TNF antibodies

The T cell cytokine IL-17 and the Th-17 pathway appear to have a role in the pathogenesis of inflammatory bowel diseases. IL-2 is a potent stimulator of lymphocyte proliferation and IL2/IL21 receptor polymorphisms have recently been associated with susceptibility to IBD. To evaluate the expression of IL-17, IL-2 and TNFα in Crohn's disease (CD) patients with and without anti-TNFs. Cytokine expression was evaluated by ELISA and intracellular staining of CD4(+) T-cells from the peripheral blood and lamina propria of CD patients and of non-IBD controls. The results were stratified by disease activity and anti-TNF treatment. IL2 expression was significantly elevated in CD patients not treated with anti-TNFs in comparison to healthy controls (19.6% vs. 33.3%, P=0.03) and CD patients treated with anti-TNFs (20.4% vs. 33.3%, P=0.02), and similar in infliximab-treated patients and controls. IL17 expression was similar in CD patients and controls, and was not affected by anti-TNF therapy. TNFα expression in patients with active CD was increased compared to controls (35.5% vs 25.7%, P<0.005), and was significantly decreased in anti-TNF treated patients in comparison to CD patients without anti-TNFs (39.6% vs 26.2%, P=0.01). Expression of IL2 was significantly decreased in anti-TNF-treated CD patients in comparison to non-treated CD patients and controls. This novel finding may indicate a further mechanism of anti-TNF therapy in CD. Expression of IL17 was not influenced by presence of CD or anti-TNF therapy, which may partly explain the failure of recent clinical trials investigating anti-IL17 therapy in CD.

Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide.

Methotrexate has been used an immunomodulator in many autoimmune diseases, including inflammatory bowel disease. However, many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios: (1) steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti-TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD; (6) management of fistulizing disease in CD; and (7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.

Response to biologic therapy in Crohnʼs disease is improved with early treatment: An analysis of health claims data

Anti-tumor necrosis factor (TNF) therapy is an important treatment option for management of active Crohn's disease (CD) and is labeled for use after failure of conventional therapy (step-up). However, there is debate on the introduction of anti-TNF agents earlier in the treatment strategy (top-down) to potentially improve clinical outcomes. The aim of this study was to determine if a top-down approach with anti-TNF therapy is associated with improved outcomes for patients with active CD. Claims data were from adult patients with CD with continuous enrollment in the same health plan for ≥ 6 months prior to the initial diagnostic claim for CD, ≥ 12 months after their initial anti-TNF claim, and with ≥ 1 anti-TNF claims after their initial diagnosis for CD. Three patient groups were identified: The Step-Up group used 5-aminosalicylates and/or corticosteroids prior to anti-TNF; the immunosuppression (IS)-to-TNF inhibitor group used IS prior to anti-TNF therapy; the Early-TNF group initiated anti-TNF therapy within 30 days of the first prescription for CD. Response to anti-TNF therapy was determined up to 24 months following anti-TNF initiation by concomitant corticosteroid use, CD surgery, anti-TNF dose escalation, and anti-TNF discontinuation/switch. A top-down approach to anti-TNF therapy was associated with a lower risk of concomitant corticosteroid use, anti-TNF dose escalation, discontinuation/switch of anti-TNF, and CD-related surgery compared with the step-up and IS-to-TNF therapy approaches. These "real-world" data show that a top-down approach to anti-TNF therapy in CD is associated with reductions in loss of response and fewer surgeries than conventional step-wise management.

Changes in acute phase proteins after anti-tumor necrosis factor antibody (infliximab) treatment in patients with Crohn´s disease.

Acute phase proteins and markers of proteosynthetic activity reflect the clinical activity in Crohn's disease (CD). The impact of anti-tumor necrosis factor antibody (anti-TNF) therapy on serum levels of acute phase proteins and proteosynthetic markers was studied. Fourteen patients with active CD were treated with 5 mg per kg of anti-TNF in intravenous infusion. Clinical activity (assessed by Crohn's disease activity index - CDAI), alpha-1-acid glycoprotein, haptoglobin, cholinesterase and prealbumin were assessed before and in months 1 and 5 after treatment. A sustained decrease in CDAI was observed. This was accompanied by a significant decrease in alpha-1-acid glycoprotein and haptoglobin in month 1 (p=0.005 and p=0.01, respectively) while in month 5 the levels of both acute phase proteins rose significantly (p=0.003 for alpha-1-acid glycoprotein and p=0.02 for haptoglobin). Cholinesterase and prealbumin significantly increased in month 1 after the treatment (p=0.02 and p=0.0006, respectively), the increase was sustained in cholinesterase while prealbumin levels diminished in month 5. We conclude that the clinical improvement after anti-TNF therapy for CD is accompanied by changes of acute phase proteins and proteosynthetic markers. The assessment of these laboratory markers may be useful in the management of CD patients treated with anti-TNF.