Long-term Effectiveness Of Infliximab Research Articles

Long-term Experience with Anti-tumor Necrosis factor- α Therapy in the Treatment of Refractory, Non-infectious Intermediate, Posterior, and Panuveitis

ABSTRACT Purpose To study the efficacy and long-term effects of infliximab and adalimumab in patients with active refractory non-infectious intermediate, posterior, or panuveitis (NIPPU). Methods Retrospective, longitudinal study. Results Included were 61 patients (104 eyes) of whom 34 were males (55.74%). Mean age at diagnosis of uveitis was 26.5 ± 16.14 years. All patients had active uveitis at baseline (time of initiation of biological therapy). Median interval between the start of conventional immunomodulatory therapy (IMT) to the introduction of biological therapy was 13.0 (IQR 26.0) months. Ocular inflammation was effectively controlled in 92 eyes (88.46%). The most commonly used TNF-α inhibitor was adalimumab in 47 patients (77%). Mean follow-up time after baseline was 40 ± 34.08 months. In the year preceding the institution of TNF-α inhibitors, the average number of flares was 1.5 ± 1.1/year and it decreased to 0.08 ± 0.29/year in the first year after baseline (p < .0005). Forty-four eyes (42.30%) experienced flare over the entire follow-up period. Mean time to first flare was 14.5 ± 9.26 months. At baseline, the mean dose of prednisone was 25.5-±20.8 mg/day. A marked decrease to a mean prednisone dose of 7.85 ± 9.7 mg/day was observed at 6 months (p = .03). In patients treated with adalimumab, the mean time to prednisone dose ≤7.5 mg/day was 4.02 ± 4.89 months compared to 15.64 ± 21.34 months in patients treated with infliximab (p = .03). 64.3% of patients treated by infliximab had Behçet uveitis compared to 27.7% of patients treated by adalimumab. Eyes treated with adalimumab experienced first flare at a mean time of 14.11 ± 6.29 months, whereas eyes treated with infliximab experienced first flare at 18.29 ± 14.24 months after baseline (p < .0005). The risk for moderate and severe visual loss was lower with shorter duration of uveitis before initiating anti-TNF-α treatment (odds ratio, 0.003; 95% CI, 0.000–0.005; p = .023), better presenting logMAR VA (odds ratio, 0.266; 95% CI, 0.172–0.361; p < .0005) and when adalimumab was used (odds ratio, 0.354; 95% CI, 0.190–0.519, p < .0005). Conclusions Anti-TNF-α therapy was successful in controlling refractory NIPPU in the majority of cases. It significantly reduced flare rate, exerted steroid-sparing effects, and preserved visual potential. Adalimumab use, better initial visual acuity, and earlier introduction of anti-TNF- α therapy were associated with a lower risk of visual loss.

OP06 The influence of different prednisolone tapering algorithms on the effectiveness of infliximab in patients with Ulcerative Colitis – A real-world cohort study

Abstract Background Data regarding the influence of prednisolone tapering on clinical outcomes among patients with ulcerative colitis (UC) are limited. We aimed to investigate the influence of different prednisolone tapering algorithms on the effectiveness of infliximab (IFX) among patients with UC. Methods This Danish retrospective single-center study included all patients with UC who were treated with IFX between 2009 and 2019 at Herlev University Hospital. The patients were grouped according to the prednisolone tapering: standard (≤5 mg/week), fast (&amp;gt;5 mg/week), or direct discontinuation after an initial course of less than one week. Finally, we included a control group of patients treated with IFX monotherapy. The primary outcome was corticosteroid-free clinical remission at weeks 14 and 52 defined as a partial Mayo score ≤1. Variables with a p-value ≤0.20 in univariable regression analysis were included in multivariable analysis. A subgroup analysis containing patients with acute severe ulcerative colitis (ASUC) treated with at least 40 mg of prednisolone at initiation of IFX was performed. Results The study included 148 patients with UC of whom 81 (54.7%) were treated with prednisolone at the initiation of IFX. No association between prednisolone tapering and corticosteroid-free clinical remission with IFX at weeks 14 or 52 was observed (Figure 1 and Table 2). However, a higher proportion of patients in the standard tapering group achieved a C-reactive protein (CRP) level less than 5 mg/L at week 14 as compared with the fast-tapering group (23/23 (100%) vs. 14/18 (77.8%); p=0.03) and directly discontinuation group (6/10 (60%); p=0.03). This difference was not explained by prednisolone usage. In addition, none of the patients within the standard tapering regime (0/24; 0%) had severe activity at week 14 whereas this was seen in 4/19 (21.1%) in the fast tapering regime (p=0.03). In the subgroup analysis of 33 patients with ASUC, the standard tapering algorithm was associated with higher clinical remission as compared with the fast tapering regime at week 14 (9/14 (64.3%) vs. 5/19 (27.8%); p=0.02) and clinical response or remission at week 52 (12/14 (85.7%) vs. 7/19 (36.8%); p=0.01, Figure 2). Conclusion This study demonstrated no overall impact of prednisolone tapering algorithms on short and long-term effectiveness of IFX in patients with UC. However, standard tapering resulted in lower CRP levels and fewer cases of severe disease activity in the overall cohort and higher rate of short and long-term clinical response among ASUC patients, as compared with fast tapering regimes. Taken together, the data indicate that longer corticosteroid exposure in patients with high disease burden might improve IFX responses.

Comparison of Long-term Outcomes of Infliximab versus Adalimumab in 1,488 Biologic-Naive Korean Patients with Crohn's Disease.

Background/AimsData on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the key clinical outcomes (surgery, hospitalization, and corticosteroid use) of use of these two drugs in biologic-naive Korean patients with CD.MethodsUsing National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016.ResultsWe included 1,488 new users of biologics (1,000 IFX users and 488 ADA users). Over a median follow-up period of 2.1 years after starting biological therapy, no significant differences were found between IFX and ADA users in the risks for surgery (ADA vs IFX adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 0.81 to 1.84), hospitalization (aHR, 1.02; 95% CI, 0.81 to 1.28), and corticosteroid use (aHR, 0.82; 95% CI, 0.56 to 1.19). These results were unchanged even when only patients who used biologics for over 6 months were analyzed (aHR [95% CI] surgery, 1.31 [0.82 to 2.11]; hospitalization, 1.02 [0.80 to 1.30]; corticosteroid use, 0.80 [0.54 to 1.18]). Additionally, these results were unchanged in patients treated with biologics as monotherapy or in combination with immunomodulators.ConclusionsIn this nationwide population-based study, no significant difference was found in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study indicates that the selection of one of these two biologics can be determined by patient and/or physician preference.

P405 Comparison of long-term outcomes of infliximab vs. adalimumab in 1488 biologic-naive Korean patients with Crohn’s disease

Abstract Background Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the clinically key outcomes (surgery, hospitalisation, and corticosteroid use) of these two drugs in biologic-naive Korean patients with CD. Methods Using National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016. Results We included 1488 new users of biologics (1000 IFX users and 488 ADA users). Over a median follow-up of 2.1 years after starting biological therapy, there were no significant differences in the risk of surgery (ADA vs. IFX; adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 0.86–1.95), hospitalisation (aHR, 1.05; 95% CI, 0.84–1.32), and corticosteroid use (aHR, 0.84; 95% CI, 0.58–1.22) between IFX and ADA users. These results were unchanged even when only patients who used biologics for over 6 months were analysed (aHR [95% CI]; surgery: 1.41 [0.88–2.26], hospitalisation: 1.06 [0.83–1.35], and corticosteroid use: 0.82 [0.56–1.21]). Additionally, these results were stable in patients treated with biological monotherapy or combination therapy with immunomodulators. Conclusion In this nationwide population-based study, there was no significant difference in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study supports that the choice of one of these two biologics may be allowed to be determined by the preference of patients and/or physicians.

Long-term safety and efficacy of infliximab for the treatment of ankylosing spondylitis.

The introduction of TNFα blockers has revolutionized the treatment of ankylosing spondylitis (AS). The objectives of this review are to summarize the most up-to-date data on long-term efficacy and safety of infliximab in AS, with special emphasis on axial and extra-articular disease, predictors of response, and radiological response. The general consensus of this literature search was that infliximab is highly efficacious in the treatment of AS. Most studies have demonstrated good clinical outcomes after 3 years of treatment, as measured by Spondyloarthritis International Society response in 75%–85% of treated AS patients. Reports on the long-term effects of infliximab as documented by radiological findings, however, are controversial. While some studies reported a similar progression rate as that of the historical OASIS cohort, others have suggested that infliximab may halt new bone formation. The long-term safety of infliximab is well known, mainly from data stored in national registries. While it has been suggested that side effects of infliximab may be fewer in AS compared to rheumatoid arthritis, data on this issue are sparse, with most of the information on long-term safety pertaining to rheumatoid arthritis. It can however be concluded that the long-term efficacy of infliximab is apparently maintained in AS and with an acceptable safety profile.

Extent of Early Clinical Response to Infliximab Predicts Long-term Treatment Success in Active Ulcerative Colitis.

The long-term effectiveness of infliximab (IFX) in ulcerative colitis (UC) and predictors of treatment response remain poorly characterized. A retrospective cohort study was conducted in 213 consecutive patients with active steroid-refractory or steroid-dependent UC treated with induction and scheduled maintenance IFX at an inflammatory bowel disease referral center. Outcomes included annual steroid-free remission (SFR), IFX failure with discontinuation, colectomy, and serious adverse events. The 1- and 5-year cumulative probabilities for SFR were 39% and 14%, for IFX failure were 31.7% and 55.6%, and for colectomy were 19.2% and 37.4%, respectively. A sensitivity analysis considering the last clinical observation in patients with incomplete follow-up demonstrated a long-term SFR rate of 36%. Among responders to IFX induction therapy, achieving clinical remission before maintenance IFX therapy predicted SFR at 1 year (adjusted odds ratio = 4.50; 95% CI, 1.75-11.53), whereas the need for IFX dose intensification during the first year of therapy predicted a lower odds of SFR at 1 year (adjusted odds ratio = 0.28; 95% CI, 0.11-0.67) and a greater hazard of IFX failure beyond 1 year (adjusted hazard ratio = 2.57; 95% CI, 1.14-5.81). Older age and shorter UC duration at IFX initiation predicted poorer long-term outcomes. In patients with moderate-to-severe UC treated with scheduled IFX at an inflammatory bowel disease center, close to half of the patients are still on IFX at 5 years, although a smaller proportion of patients achieve long-term SFR. The magnitude and stability of early response to IFX is associated with long-term therapeutic benefit to this agent.

Long-Term Efficacy of Infliximab for Treatment of Severe Behcet’s Uveitis

Introduction: Behcet’s uveitis is a serious sight-threatening condition that may lead to blindness if not appropriately managed. The aim of the present study is to evaluate long-term effectiveness of infliximab in resistant Behcet’s uveitis. Methods: Medical records of 32 patients (56 eyes) were retrospectively analysed. Primary outcomes included ocular inflammatory activity, frequency of uveitis attacks and steroidsparing effect. Results: Mean follow-up was 33,2 months while mean age of patients at disease onset was 33,3 years. Ocular inflammation was bilateral in 75% of cases and consisted in panuveitis in 46,4 % of affected eyes. All patients received intravenous infusions of infliximab (5mg/kg) at weeks 0, 2, 4, 6 and every 6-8 weeks thereafter. Clinical remission was observed in 26 out 32 patients (81,2%). Mean number of uveitis attacks decreased from 2,56 to 0,65 during infliximab therapy (p<0.001) while systemic corticosteroids were tapered in 17 patients and suspended in 10 (31,2%). Conclusions: Our study suggested that infliximab is long-term effective in resistant Behcet uveitis, improving visual prognosis and stabilising clinical course of disease in a large cohort of patients with various pattern of BD including neuro-behcet forms.

AB0825 Investigation of Effects on Bone Metabolism of Anti-TNF BIOLOGICS and Bisphosphonates in Patients with Rheumatoid Arthritis

BackgroundTreatment for rheumatoid arthritis has become to obtain remission as biologics are widely used. Nonetheless, the main target of the treatment is synovitis and evaluation and treatment for osteoporosis with...

AB0082 The efficacy of anti-tnf treatment on urinary type-ii collagen c-telopeptyde levels in patients with rheumatoid arthritis

BackgroundThe aim of the present study was to evaluate the efficacy of anti-TNF treatment on urinary type-II collagen C-telopeptyde (CTX-II) levels which is a cartilage destruction marker in patients with...

Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases

Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5% with AS, 22.5% with CD, and 45% with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.

Long-Term Effects of Intravitreal Infliximab for Treatment of Sight-Threatening Chronic Noninfectious Uveitis

This study aimed to evaluate the safety and long-term effects of infliximab on chronic noninfectious uveitis with measuring best corrected visual acuity (BCVA) and central macular thickness (CMT). Ten eyes of 7 patients were included in this prospective case series. All the patients had noninfectious anterior and posterior uveitis that was unresponsive to conventional treatments for 3 months. About 1.5 mg of infliximab in 0.15 cc was injected intravitreally and the patients were followed for 6 months. BCVA was measured by Snellen chart and grading of vitritis was measured according to binocular indirect ophthalmoscope score before injection, 4 weeks, 3 months, and 6 months after the injection. CMT was measured 1 day before injection and compared with the same factors 4 weeks and 6 months after the injection. Mean of LogMAR before injection was 1.37±0.43 that changed to 0.67±0.55 and 1.38±0.36 one month and 6 months after the injection, respectively. Mean CMT before injection was 673.2±338.39 that changed to 456.4±317.46 and 659.3±342.48, 4 weeks and 6 months after the injection, respectively. Mean vitreous haziness grade before injection, 4 weeks, 3 months, and 6 months after the injection was 2.7, 0.95, 2.3, and 2.6, respectively. Intravitreal Infliximab may be used in treatment of noninfectious uveitis. It probably improves the vision and decreases the macular edema but its effect is temporary and repeated injections may be needed to achieve the best therapeutic goal.

Sa1891 Long-Term Effect of Infliximab Against Postoperative Recurrence of Mucosal Lesions in Patients With Crohn's Disease

Background & Aims: It has been shown that infliximab (IFX) has short-term protective effect against postoperative recurrence in patients with Crohn's disease (CD), suggesting the role “reset” therapy for aggressive CD. However, long-term effect of IFX in postoperative CD remains to be elucidated. We aimed to investigate long-term effect of scheduled IFX against postoperative recurrence of intestinal lesions in patients with CD. Methods: Postoperative clinical course of 37 patients with CD, who underwent intraoperative enteroscopy (IOE) and ileocolonic resection, was retrospectively investigated. In each patient, endoscopic/ radiographic findings after surgery were reviewed. Recurrence at the anastomotic site was defined by an endoscopic score >i2 of Rutgeerts' score or by depiction of small barium flecks indicating erosion or ulceration, thickened mucosal folds, or intestinal narrowing under double-contrast barium enteroclysis. Recurrence outside the anastomotic site was regarded to be positive when active inflammatory lesions were endoscopically or radiographically detected in the intestinal segment where preceding IOE had not identified any active lesion. Age, disease duration, history of intestinal resection, disease type, extent of disease, perianal disease, active inflammatory lesions under IOE, smoking habit, and postoperative treatments were also reviewed. Results: 19 of 37 patients were treated by scheduled IFX (5mg/kg, every 8 weeks). 17 patients (46%) showed postoperative recurrence. Time interval between surgery and confirmation of recurrence was 26.9±18.7 months. 3 of 17 patients with recurrence were under IFX. Active inflammatory lesions were detected in the anastomotic region in 10 patients, outside the anastomotic region in 5, and both in 2. Univariate analysis revealed that history of intestinal resection (Log-rank test: p=0.047), penetrating disease (p=0.01), current smoking habit (p=0.039) and ileocolonic anastomosis (p=0.046) were more frequent in patients with recurrence than in those without. In addition, recurrencewas less frequent in patients with IFX than in thosewithout (p=0.014).Multivariate analysis revealed that patients treated with IFX were less likely to recur (Cox proportional hazards model: OR=0.08, 95% CI 0.009-0.43), while patients with history of intestinal resection had an increased risk of recurrence (OR=9.97, 95% CI; 1.71-98.1). Stratified analyses revealed that in patients treated by IFX, recurrence was less frequent in patients with concomitant immunomodulators than in those without, although the difference did not reach a statistical significance (0% vs. 21%, p=0.11). Conclusions: Scheduled IFX treatment after intestinal resection can exert a longer prophylactic effect in postoperative CD. Intensive postoperative treatment seems to be necessary for patients who require repeated surgery.

Long-term effects and colectomy rates in ulcerative colitis patients treated with infliximab: A Danish single center experience

Objective. Infliximab (IFX) is a well-established treatment for both acute, severe ulcerative colitis (UC) and chronic, refractory UC. However, data on the long-term clinical outcome and colectomy rates after IFX treatment in a routine clinical setting are sparse. The aim of this study was to provide further data on the long-term effect of IFX for acute, severe and chronic, refractory UC in unselected patients treated at a single center. Material and Methods. A retrospective analysis of all patients (n = 52) treated with IFX for UC before February 2009 was performed. The material comprised 19 patients (37%) with acute, severe UC and 33 patients (63%) with chronic, refractory UC. The primary outcome was colectomy rate; the secondary outcome clinical response. Results. The overall colectomy rate was 27% (14/52 patients) after a median follow-up of 22 months (range 4–57 months). The colectomy rate was 37% (7/19 patients) in the group with acute, severe UC and 21% (7/33 patients) among those with chronic, refractory UC. In all, 77% of the patients had clinical response to IFX treatment with no difference between the two subgroups. Among those with an initial clinical response, 50% (20/40 patients) had sustained clinical response. Conclusion. IFX is of long-term benefit as rescue treatment in selected patients with acute, severe UC with about two-thirds of the patients avoiding colectomy. The beneficial effect on colectomy rate in chronic, refractory UC seems less convincing although these patients may still achieve a sustained clinical response.

Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort

Background and aims:This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn’s disease (CD) from a single centre during a median follow-up of...

Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis

Background:Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor α (TNFα). Therefore, we tested...

Infliximab and the risk of latent viruses reactivation in active Crohnʼs disease

Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein-Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/10(5) Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring.

LONG-TERM OUTCOME OF TREATMENT WITH INFLIXIMAB IN 440 CROHN'S DISEASE PATIENTS: RESULTS FROM A SINGLE CENTER COHORT

Background & Aims: This observational study assessed long term clinical benefit of infliximab (IFX) in 614 consecutive Crohn9s disease (CD) patients from a single centre during a median follow-up (FU) of 55 months (IQR 27-83). Methods: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of FU. Long-term effects of IFX on the course of CD as reflected by the rate of surgeries and hospitalizations and need for corticosteroids were also analyzed. Results: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term therapy. In 68.3% of these therapy with IFX was ongoing and in 31.7% IFX was stopped with the patient being in remission. Seventy patients (12.8%) had to stop IFX for side effects and 118 (21.6%) for loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalizations and surgeries decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. Conclusions: In this large real-life cohort of CD patients long-term therapy with IFX was very efficacious to maintain improvement during a median FU of almost 5 years and changed disease outcome by decreasing the rate of hospitalizations and surgeries.

Endoscopic and histologic evidence of persistent mucosal healing and correlation with clinical improvement following sustained infliximab treatment for Crohn's disease

ABSTRACTObjectives: The long-term effect of infliximab on endoscopic and histologic disease activity and expression of inflammatory markers was assessed in Crohn's disease patients who received infliximab as episodic or scheduled maintenance therapy over 54 weeks (ACCENT I).Methods: All patients received infliximab 5 mg/kg at week 0 and at week 2 were then randomized as responders or nonresponders to placebo or infliximab (5 or 10 mg/kg). Patients received placebo or infliximab 5 mg/kg at weeks 2 and 6 followed by placebo or infliximab (5 or 10 mg/kg) every 8 weeks or episodically on loss of response. Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), Inflammatory Bowel Disease Questionnaire (IBDQ), and colonic and ileal Global Histologic Disease Activity (CGHAS and IGHAS) scores were determined at weeks 0, 10, and 54. Tumor necrosis factor-alpha (TNF‐α), gelatinase B, infliximab, tenascin, clusters of differentiation marker 68 (CD68), and intercellular adhesion molecule‐1 (ICAM‐1) were detected in mucosal biopsies by immunohistochemistry.Results: At baseline, CDEIS significantly correlated with CGHAS only. Further at baseline, both CDEIS and the worst CGHAS or IGHAS, were significantly correlated with CD68, ICAM‐1, and gelatinase B expression. At week 10, improvement in CGHAS only, correlated significantly with better CDAI, CDEIS, and IBDQ scores. Improvements in CDEIS and GHAS at week 10 correlated with reductions in gelatinase B and CD68, whereas only GHAS improvement correlated with decreased TNF‐α expression. At week 54, decreased gelatinase B expression continued to correlate with improved CDEIS and GHAS while decreased CD68 and TNF-α expression correlated with GHAS and CDEIS improvement, respectively.Conclusions: Endoscopic and histologic evidence of mucosal healing was associated with a sustained reduction in the expression of inflammatory markers. Infliximab-induced improvement in the clinical signs and symptoms of Crohn's disease was associated with endoscopic and histologic evidence of sustained mucosal healing.

The effects of infliximab maintenance therapy on health-related quality of life

Objectives The ACCENT I study evaluated the long term effects of infliximab as maintenance therapy for patients with Crohn's disease. Health-related quality of life (HRQL) was also assessed in the trial. Methods In ACCENT I, a total of 573 patients received a single infusion of 5 mg/kg infliximab at baseline. After assessment of response at wk 2, patients were randomly assigned repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (single dose), repeat infusions of 5 mg/kg of infliximab at the same time points (5 mg/kg maintenance), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (10 mg/kg maintenance). HRQL analyses presented include the 335 patients classified as wk-2 responders. The treatment regimens were compared with regard to their change from baseline in the IBDQ and Short Form–36 (SF-36) scores. Results Baseline scores indicated substantial impairment in HRQL. Throughout the study, all IBDQ and SF-36 scores were improved at all time points compared to baseline. After wk 10 and through wk 54, these improvements were greater in the two infliximab maintenance groups than in the single-dose group. The mean change from baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group (22.1, p < 0.05) and 10-mg/kg maintenance group (30.2, p < 0.001) than in the single-dose group (8.9). Similarly, the mean change from baseline to wk 54 in the PCS of the SF-36 was greater in the 5-mg/kg maintenance group (6.1, p < 0.05) and 10-mg/kg maintenance group (7.2, p < 0.01) than in the single-dose group (2.5). Conclusions Infliximab therapy provides substantially improved HRQL as measured by both the disease-specific IBDQ and the generic SF-36. A maintenance regimen of either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg infliximab infusion in sustaining this benefit.