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Aim: To assess tumor necrosis factor-α (TNF-α), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-α therapy., Methods: Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group I) and 31 patients in complete clinical remission (Group II) selected as a control group were collected to measure trough serum TNF-α level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-α, IFX trough levels, and ATI concentrations., Results: The serum TNF-α level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them., Conclusion: On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

BACKGROUND. Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. The RASH study revealed that previous use of biological therapy and dose intensification are associated with restarting of biological therapy in Crohn's disease. The aim of the study was to assess the disease course and frequency of relapse of ulcerative colitis (UC) following discontinuation of infliximab in patients with remission and to determine predictive factors for relapse. PATIENTS AND METHODS. Fifty-one UC patients who had achieved clinical remission following 1 year of infliximab therapy and for whom infliximab was then discontinued participated in this prospective observational study. 15.7% of the patients received infliximab before the 1-year period of biological therapy analyzed in the study. Biological therapy was restarted in case of recurrent clinical activity. Data were collected from four Hungarian IBD centers. RESULTS. Thirty-five percent of the patients needed to be retreated with infliximab within 1 year after treatment cessation. Logistic regression analysis revealed that previous biological therapy (p = 0.021) was associated with the need of restarting infliximab. None of the data relating to patients' demographic and clinical characteristics, concomitant therapy and CRP level showed association with the need for restarting biological therapy. CONCLUSIONS. Biological therapy was restarted at a median of 4 months after discontinuation in more than every third UC patients who had been in clinical remission following 1 year of infliximab therapy. Response to retreatment with infliximab was favorable in the majority of the patients who relapsed.

Biological therapies are supposed to trigger the development of autoimmune diseases. We report a case of a 27-year old woman presenting with drug induced systemic lupus erythematosus (SLE) associated with infliximab therapy. The development of paradoxical inflammation in immune-mediated inflammatory diseases patients treated with anti TNF-α suggests that an unknown inflammatory pathway may be provoked by inhibiting TNF-α. We suppose that in our case a cross reactivity between anti-infliximab antibodies and autoantibodies may lead to the development of TNF-induced immune disease., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy., Aim: To assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse., Methods: One hundred twenty-one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty-seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points., Results: Biological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1-year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053)., Conclusions: Biological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients., (© 2012 Blackwell Publishing Ltd.)

BACKGROUND & AIMS. Secondary loss of response is a frequent event occurring during biological therapy. The aim of this study was to assess loss of efficacy in patients with Crohn's disease treated with infliximab or adalimumab for a year. The secondary goals were to identify clinical or laboratory predictors of loss of response. METHODS. Sixty-one Crohn's disease patients achieved remission after the induction therapy and received regular maintenance therapy: 35 of them were on infliximab, 26 on adalimumab therapy. None of the patients treated with infliximab had received previous biological therapy, and 10 of the adalimumab-treated patients were naïve to biological therapy. The data of patients who relapsed and who remained in remission and also the characteristics of infliximab-treated patients and adalimumab-naïve patients were compared. Data were analyzed statistically. RESULTS. Remission was achieved in 70.5%; response was achieved in 29.5% of the patients after induction. Loss of response occurred in 22 of 61 patients after a year of therapy. The proportion of remission after induction was significantly lower in patients who lost response vs. those who remained in remission. More patients with sustained remission received immunosuppressive therapy before and during the biological therapy vs. those with loss of response. Loss of response was significantly more frequent and occurred earlier in adalimumab-naïve patients vs. infliximab-treated patients. CONCLUSION. The need for dose escalation should be calculated in the budget in the majority of patients, especially in adalimumab-treated patients.

Unlabelled: Secondary loss of response (initial good response followed by loss of response and flare up) is a frequent event occurring during biological therapy. The aim of this study was to assess loss of efficacy in patients with Crohn's disease treated with infliximab or adalimumab for a year. Secondary goals were to identify clinical or laboratory predictors of loss of response and to evaluate whether the frequency of dose escalation differs in patients receiving infliximab or adalimumab. Data were provided by a computerized database., Patients and Methods: Sixty-one patients with Crohn's disease achieved remission after induction therapy and received regular maintenance treatment. 35 of them were on infliximab, and 26 on adalimumab therapy. None of the patients treated with infliximab received previous biological therapy, while 10 of the adalimumab-treated patients were naïve to biological therapy. Authors compared the data of patients who relapsed with those who remained in remission and also the characteristics of infliximab-treated patients with adalimumab-naïve patients. Data were analyzed using Chi-square test. Kaplan Meier curve was used to show the time of loss of efficacy., Results: Remission was achieved in 70.5%, and response was achieved in 29.5% of the patients after induction. Loss of response occurred in 22 of the 61 patients after a year of therapy. The proportion of remission after induction was significantly lower in patients who lost response vs. those who remained in remission. More patients with sustained remission received immunosuppressive therapy before and during the biological therapy vs. those with loss of response. Loss of response was significantly more frequent and occurred earlier in adalimumab-naive patients vs. infliximab-treated patients., Conclusion: The need for dose escalation should be calculated in the budget in the majority of patients, especially in adalimumab-treated patients.