Higher Infliximab Research Articles

Sa1980 High Infliximab Trough Levels Are Associated With Better Control of Inflammation in IBD

Sa1980 High Infliximab Trough Levels Are Associated With Better Control of Inflammation in IBD

P309. High infliximab trough levels are associated with better control of inflammation in inflammatory bowel disease

P309. High infliximab trough levels are associated with better control of inflammation in inflammatory bowel disease

Higher Trough Concentrations of Infliximab are Associated with Clinical Remission and Mucosal Healing in Patients with Inflammatory Bowel Disease

Objective: Few studies have correlated the infliximab (IFX) trough concentration, clinical remission (CM) and mucosal healing (MH). The purpose of the study was to determine if higher IFX trough levels are associated with MH and CR, in a group of Brazilian inflammatory bowel disease patients. Methods: Cross-sectional study of 51 IBD patients in IFX maintenance therapy, at a medical center, in Brazil. IFX serum levels were obtained from blood samples collected immediately before drug infusion. The IFX trough levels were correlated with clinical and endoscopic scores and a univariate analysis was conducted to identify factors associated with CR and MH. Results: IFX trough concentration ≥ 2 μg/mL was associated with higher CR (84.2% vs. 28.1%; P<0.001) and MH (83.3% vs. 25.0%; P=0.001). Trough levels of 2.0 μg/mL were 89% specific for CR (sensibility=66%; P<0.001) and 89% specific for MH (sensibility =64%; P<0.001). On univariate analysis, IFX trough concentration was the only variable associated with CR and MH. Conclusion: The study found a significant association between IFX trough level ≥ 2 μg/mL, CR and MH. Therapeutic drug monitoring is an important tool in IBD patients and should routinely be performed to optimize treatment.

PTH-061 Anti-tumour necrosis factor-alfa drug monitoring in paediatric inflammatory bowel disease

Introduction The lack of familiarity with the Commercial assays to measure anti-Tumour Necrosis Factor-alfa (TNF) drug and antibody levels and the cost implication has limited their widespread clinical use. Method We have done a retrospective analysis of anti TNF-alfa drug monitoring in patients with IBD over 12 months. We have correlated anti-TNF-alfa drug levels with the presence of anti-TNF antibody, concomitant treatment with Azathioprine and the clinical remission status. We have also looked at the cost effectiveness of anti-TNF-alfa drug monitoring. Results 89 anti TNF drug and antibody levels were done in 47 patients receiving Infliximab in the last twelve months (41 patients had Crohn’s disease, 4 had ulcerative colitis and 2 had IBD unclassified). 14 patients (30%) had below therapeutic levels of Infliximab and all were receiving Infliximab 5 mg/Kg dose. 12 of these patients had Crohn’s disease and all these 12 patients were on concomitant treatment with Azathioprine. 7 of these patients (58%) had anti-Infliximab antibody positivity. Out of the 12 Crohn’s disease patients with low Infliximab levels, 3 were in deep remission with mucosal healing and these three patients were positive for anti-Infliximab antibodies. In these 3 patients treatment with Infliximab was stopped. Of the 12 patients with Crohn’s disease and low levels of Infliximab, 9 (75%) were not in clinical remission. 4 of these patients had antibody positivity and dose escalation to 10 mg/kg achieved clinical remission in only one of these patients. 5 Crohn’s disease patients who were not in clinical remission with low Infliximab levels and no anti Infliximab antibodies achieved clinical remission with Infliximab dose increase to 10 mg/kg. 4 patients had Infliximab concentrations higher than the therapeutic range and all these patients were on 10mg/kg dose. 15 patients (32%) had anti-Infliximab antibody positivity and all these patients had Crohn’s disease. 7 of these patients had low Infliximab levels, 2 had high Infliximab levels (on 10 mg/kg dose) and 6 had Infliximab levels in therapeutic range. 14 of these patients were receiving concomitant Azathioprine. Out of these 15 patients, 9 were in clinical remission. Overall cost savings of about 9000 GBP per year were achieved by Infliximab dose adjustment, even after considering the cost of these investigations and the cost of increased dose of Infliximab in some patients. Conclusion Anti-TNF-alfa drug level and antibody monitoring are very useful and cost effective in the management of children with inflammatory bowel disease Disclosure of interest R. Muhammed Grant/ Research Support from: MSD immunology, Abbvie, Tillotts Pharma, Consultant for: Abbvie, Speaker Bureau of: Abbvie, MSD Immunology, T. Wong: None Declared, W. Haller: None Declared, R. Bremner: None Declared, S. Protheroe Consultant for: MSD Immunology, Conflict with: MSD Immunology.

Tu1307 Using Serum Infliximab Drug and TNF Cytokine Concentration to Predict Clinical Outcome After High-Dose Infliximab in the Treatment of Severe Ulcerative Colitis: A Pilot Study

Background: Over 50% of hospitalized patients with severe ulcerative colitis (UC) require emergent colectomy despite receiving standard dose infliximab (IFX) at 5 mg/kg. Proposed reasons for failure include rapid clearance of IFX from the serum due to fecal loss of IFX, prompting some centers to empirically prescribe high dose IFX at 10 mg/kg. While this strategy is reasonable, the acute pharmacokinetics of this strategy is unknown and reasons for failure using this strategy are poorly described. Methods: In a prospective pilot study, 11 adult hospitalized patients (7 men, 4 women) with severe UC confirmed by sigmoidoscopy (UCDAI > 6, Mayo endoscopic subscore > 2) received 10 mg/kg of IFX within 3-5 days of initiating IV steroids. Measurement of IFX drug concentration and TNF-alpha levels occurred at baseline and at 24, 48, and 72 hours, and at 1 and 2 weeks after the initial infusion. MadCam (mucosal vascular addressin cell adhesion molecule) cytokine concentration served as a control. The association between these markers and surgery was analyzed. Results: Three patients required colectomy within the 8 week study period (27%). Median IFX drug concentration was comparable in the colectomy and no colectomy groups at all time points. While drug concentration at any time point did not discriminate between the two groups, the response of TNF-alpha cytokine concentration to IFX did. Both groups had similar TNF concentration at baseline, however the colectomy group had higher TNF concentration 24 hours after TNF inhibitor therapy (p=0.03). Control MadCam concentration was similar and unchanged in both groups receiving TNF inhibitor therapy. Conclusion: Our study suggests lower IFX drug concentration is not an important mechanism for TNF-inhibitor failure in severe UC patients receiving high dose IFX, however response to TNF inhibition as measured by TNF concentration at 24 hours is. Larger cohorts are needed to define the role of using cytokine response to biologic therapy to help elucidate the mechanism and predict biologic failure in this high risk group.

Tu1282 Azothioprine or 6-Mercaptopurnine Dose Does Not Effect Serum Infliximab Level or Rate of Antibody to Infliximab Formation

Background: Combined immunomodulator (IMM) and biologic therapy is superior to either therapy alone in inflammatory bowel disease (IBD) patients. This is thought to be a result of increased serum infliximab (IFX) level and decreased rates of antibody to infliximab (ATI) formation in combination therapy patients. A previous study did not show an association of IMM dose to serum IFX levels or ATI formation; rather only 6 TG levels were predictive of IFX levels and ATI formation. Our aim was to determine if IMM dose influenced IFX level and ATI formation in a larger IBD cohort. Methods: This was a retrospective analysis at a single tertiary care IBD center. Patients with a history of IFX use for IBD who had serum IFX levels tested using Prometheus serum IFX/ATI assay were included in the study. Demographic information, disease type, SIBDQ score, IBD activity score, IBD duration to PROMETHEUS date, IFX duration, IMM type, IMM daily dose, IMM mg/kg dose, and albumin closest to IFX test were recorded. Serum IFX levels did not follow a normal distribution so data was divided into quartiles for analysis: low/undetected IFX 19.55 ug/mL. Results: Overall, 269 patients were included. There was no significant difference in demographic or disease characteristics between serum IFX quartiles (table 1). There were 99 AZA/6MP users with average weight-based dose 0.95 mg/kg (range 0.2-2.4 mg/kg). The low/undetectable IFX quartile had a larger percentage of patients not using IMMs, compared to other quartiles (p=0.01). AZA/6MP users were in higher proportion in therapeutic and high/medium high groups than in low/undetected group (p=0.05). Also, MTX users were in a greater proportion in higher IFX level quartiles (p=0.04). There was no difference in AZA/6MP daily dose or weight based (mg/kg) dose between quartiles (p=0.49 and p=0.73). Regression analysis of AZA dose showed no correlation with serum infliximab levels (p= 0.88). Patients on any dose of IMM were less likely to develop ATI than patients not on IMM (10 % vs. 24%; p=0.03). The greatest proportion of patients with ATI were in the low/undetectable IFX quartile (p =0.001). Serum albumin levels were similar among serum IFX level quartiles (p=0.07) but showed a very weak correlation with serum IFX levels (cor= 0.13, p=0.048) (table 2). Conclusions: Our study found that IBD patients on any dose of IMM are less likely to have a low serum IFX level or develop ATI than those not on IMM therapy. Our trial confirms a prior study's results that IMM dose does not affect IFX level or ATI formation rates. These findings suggest that even low dose concomitant IMM therapy may be effective at maintaining adequate serum IFX levels and preventing ATI development. Table 1

Clinical study of infliximab in treatment of patients with juvenile idiopathic arthritis

Objective To explore the clinical efficacy, adverse effect and prognosis of infliximab in treatment of the patients with juvenile idiopathic arthritis (JIA). Methods Thirty-two cases of infliximab-treated JIA patients and 30 cases of JIA control patients were investigated in this prospective study, and their tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analog scale for general health (GH), disease activity score (DAS) 28, as well as adverse reactions of treatment and follow-up outcomes were analyzed.The infliximab-treated patients were intravenously infused with infliximab at the low dose of <5 mg/(kg·time) or the high dose of ≥5 mg/(kg·time) in 0, 2nd, 6th, 14th, 22nd, 30th week.The JIA control patients were treated with conventional therapy. Results The treatment of infliximab ameliorated the TJC, SJC, ESR, GH, CRP and DAS28 of JIA patients.In the dynamical analysis of these clinical indexes of the infliximab-treated JIA patients, the index of SJC was found to fall firstly in the 2nd week, the indexes of TJC, ESR, GH and DAS28 were found to decline se-condly at 6th week, the indexes of TJC, SJC, ESR, CRP and DAS28 continued dropping till 22nd week, and only the index of GH progressively declined to 30th week.The high-dose infliximab-treated group had lower levels of ESR, GH and CRP than the low-dose infliximab-treated group(t=2.14, 3.04, 2.33, P=0.04, 0.01, 0.04). But there were no statistical difference in TJC, SJC, DAS28 and the incidence of recent adverse reactions between the high and low infliximab dose groups.In the infliximab treated group, 2 cases of patients (6.25%) failed in the therapy of infliximab; 9 cases of patients (28.13%) continued therapy with infliximab to 46th-62nd week; 7 cases of patients (21.88%) stopped therapy with infliximab in the 30th week had good improvement of joint symptoms and inflammatory indexes; 14 cases of patients (43.75%) relapsed and retreated by infliximab after cease the first course of treatment; 1 case of patient died of severe chickenpox infection after therapy with infliximab was ceased. Conclusions Infliximab can alleviate the joint symptoms, inflammatory indexes and DAS28 of JIA patients, and is an effective and safe therapy for JIA patients in the short-term study. Key words: Juvenile idiopathic arthritis; Infliximab; Therapy

Su1371 High Infliximab Trough Levels Are Associated With Impaired Quality of Life in IBD Patients in Clinical and Biochemical Remission on Maintenance IFX Therapy

Su1371 High Infliximab Trough Levels Are Associated With Impaired Quality of Life in IBD Patients in Clinical and Biochemical Remission on Maintenance IFX Therapy

P470 High infliximab trough levels are associated with impaired quality of life in IBD patients in clinical and biochemical remission on maintenance IFX therapy

P470 High infliximab trough levels are associated with impaired quality of life in IBD patients in clinical and biochemical remission on maintenance IFX therapy

Detection of Anti Infliximab Antibodies in Patients with Inflammatory Bowel Disease (IBD) in the Presence of Infliximab by Homogeneous Liquid Phase Anti Infliximab Mobility Shift Assay

Purpose: Trough levels (TL) as well as c-max levels have been positively associated with efficacy and negatively with immunogenicity of infliximab (IFX) in patients with IBD. Degradation of IFX is mainly determined by the presence of anti drug antibodies (ADA), increasing its clearance between 1.4 and 2.7 fold. With evidence accumulating in favour of the concept of therapeutic drug monitoring, standard enzyme linked immunosorbent assays (ELISA) for the detection of ADA reach their limits, as the presence of high IFX levels strongly interferes with the detection of ADA. Here we assess the perfomance of a new assay for the detection of ADA at midinfusion timepoints as compared to samples immediately prior to the next IFX infusion. Methods: 90 consecutive patients with established IBD (66 with Crohn's disease, 24 with Ulcerative Colitis) under maintenance therapy with IFX were asked to participate. Serum samples were acquired at half time between two infusions and immediately prior to the subsequent infusion. IFX drug levels were measured by ELISA (Immundiagnostik, Germany) and ADA were assessed by homogeneous liquid phase anti Infliximab mobility shift assay (HLPA) (Prometheus Labs Inc. CA) for all time points. Results: Patients were receiving a median dose of IFX of 5,51 mg/kg body-weight (4,08-10,94), yielding a median TL of 8.98 yg/ml IFX. Infliximab serum levels were significantly higher at mid infusion versus TL (p=0.000). ADA were detectable in 19 patients and 23 patients at mid infusion and trough timepoints, respectively. 17 patients were concordantly positive, 2 were positive soley at mid infusion and 6 at time of trough sampling. The agreement for the outcome positive ADA measured at week 4 versus week 8 yields a Cohen's kappa of 0,80, with a correlation of t=0,651 (p=0.001). ADA occurred most frequently in patients with non-detectable or very low TL (Table 1).Table: IFX trough levels and presence of ADAConclusion: With HLPA, it is feasible to detect ADA against IFX with excellent accordance not only at low levels of circulating infliximab but also earlier within an infusion interval, when IFX concentrations are high and interfering with conventional ELISAs. ADAs are preferrentially detected in patients with negative or low TLs. Disclosure: The work presented here was supported by Prometheus Labs Inc. who performed the mentioned analyses free of charge. This research was supported by an industry grant from Pormetheus Labs Inc.

Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

BackgroundTo get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort studyMethodsIn a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (<1 mg/l) and high (>5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis.Results147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (<1 mg/L) and 14% (95%CI 5–22) high trough levels (>5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels.ConclusionsLow (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients.

High intra-uterine exposure to infliximab following maternal anti-TNF treatment during pregnancy

Typically, inflammatory bowel disease (IBD) patients are in their reproductive years, raising questions about safely using antitumour necrosis factor antibodies like infliximab (IFX) during pregnancy. IgG antibodies naturally cross the placenta, especially during the last trimester. To prevent foetal intra-uterine exposure, stopping IFX treatment at gestational week 30 is recommended. However, whether this limits intra-uterine and early postnatal IFX exposure is unestablished. To determine the intra-uterine exposure to IFX following maternal treatment with IFX. Four pregnant IBD patients intentionally continued IFX during pregnancy. IFX levels were assessed in newborns' cord blood and the mothers' peripheral blood at delivery. The children's development during the first 3-6 months, infections, vaccine reactions and antibody responses to vaccinations against Haemophilus influenzae type b and Pneumococcus were assessed. The patients stopped IFX therapy at gestational week 21, 26, 26 and 30, respectively. In three infants, therapeutic IFX levels were present in cord blood at levels of 5.5-13.7 μg/mL and were two- to three-fold higher than in the peripheral blood of their mothers. During the 3- to 6-month follow-up, the children developed normally without signs of infections or allergic reactions, and had normal antibody titres after routine childhood vaccinations. The use of IFX until gestational week 30 leads to foetal intra-uterine exposure to IFX at levels that exceed those in the mothers' peripheral blood. Although no short-term complications were detected, the high IFX levels observed in newborns raise concerns about unknown effects of IFX on the developing immune system.

Influence of anti-infliximab antibodies and residual infliximab concentrations on the occurrence of acquired drug resistance to infliximab in rheumatoid arthritis patients

Background Infliximab (IFX) can be immunogenic for humans and lead to the formation of antibodies against IFX (anti-IFX Ab), which could induce acquired IFX resistance. Objective To test whether the presence of anti-IFX Ab and residual circulating IFX levels are associated with acquired IFX resistance in RA. Methods A multivariate logistic regression was used to analyze the relationship between anti-IFX Ab, residual IFX concentrations, and acquired IFX resistance in a nested cohort within the Swiss RA registry (SCQM-RA). Results Sixty-four RA patients on longstanding IFX therapy were included; 24 with an acquired therapeutic resistance to IFX and 40 with continuous good response to IFX. The two groups had similar disease characteristics, but patients with acquired IFX resistance required significantly higher dosage of IFX (5.4 mg/kg versus 4.3 mg/kg, p = 0.02) and shorter infusion intervals (7.1 versus 8.7 weeks, p = 0.01) than long-term good responders. The presence of residual IFX tended to be associated with a decreased risk of acquired therapeutic resistance (OR 0.4 [95% CI: 0.1–1.5]), while the presence of anti-IFX Ab tended to be associated with an increased risk of acquired therapeutic resistance (OR: 1.8 [95% CI: 0.4 – 9.0]). The presence of either high anti-IFX Ab levels or low residual IFX concentrations was strongly associated with acquired therapeutic resistance to IFX (OR 5.9, 95% CI 1.3 – 26.6). However, just 42% of patients with acquired IFX resistance had either low IFX or high anti-IFX Ab levels. Conclusion These results suggest that the assessment of anti-IFX Ab and residual IFX levels is of limited value for individual patients in routine clinical care.

Maintained clinical response of infliximab treatment in ankylosing spondylitis: A 6-year long-term study

Objectives To investigate the efficacy, safety and drug discontinuation in patients with ankylosing spondylitis treated with infliximab, as well as the drug survival over a period of 6 years. Methods Forty patients with ankylosing spondylitis treated with infliximab were included in this open label study. All patients fulfilled the New York revised criteria for ankylosing spondylitis. Infliximab was given intravenously (5 mg/kg/body weight) at weeks 0, 2, 6 and every 8 weeks thereafter for a period of 6 years. Data concerning infliximab efficacy, tolerability, adverse events and drug discontinuation, were recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index 50% and the Ankylosing Spondylitis Assessment Study Group 20% and 40% were also recorded. Results A significant improvement in the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Assessment Study Group scores was noted in the first year which sustained through the sixth year of treatment. More specifically, after the sixth year of treatment, Bath Ankylosing Spondylitis Disease Activity Index 50% was achieved by 65% of patients (26/40), Ankylosing Spondylitis Assessment Study Group 20% by 72.5% (29/40) and Ankylosing Spondylitis Assessment Study Group 40% was reached by 70% (28/40) of patients. Clinical improvement was associated with the reduction of acute phase reactants, such as C-reactive protein levels. After the first and the second year of treatment, the survival rate of infliximab reached 95%, after the third year it was 80%, while after the fourth year it was 72.5%, which was maintained throughout the fifth and sixth year of therapy. Five patients were increased the dose of infliximab and three of them had shortened the interval infusion. Overall, 11 patients were withdrawn during the observational period, three because of adverse events, two because of lack of efficacy, while six were lost from follow-up. Conclusion Infliximab was effective, safe and well-tolerated in patients with ankylosing spondylitis. The clinical response was maintained for a period of 6 years, with high infliximab survival rate, reaching the percentage of 72.5%.

405 High Infliximab Trough Levels are Associated With Mucosal Healing in Crohn's Disease

405 High Infliximab Trough Levels are Associated With Mucosal Healing in Crohn's Disease

S31 Mucosal healing in Crohn's disease is associated with high infliximab trough levels

S31 Mucosal healing in Crohn's disease is associated with high infliximab trough levels

Infliximab to Treat Chronic Noninfectious Uveitis in Children: Retrospective Case Series with Long-term Follow-up

To assess a response to infliximab therapy in childhood uveitis. Retrospective case series. We reviewed the course of 16 children with noninfectious uveitis treated with infliximab at an academic medical center. Outcome measures included incidence of uveitis recurrences, proportion of patients achieving zero or two-step decline in ocular inflammation, visual acuity, and proportion discontinuing topical glucocorticoids at zero, three, six, nine, and 12 months of therapy. Of sixteen children (29 affected eyes) with median age 11 years, six had associated extraocular inflammatory conditions. Fifteen of 16 were treated with concomitant methotrexate. Median follow-up was 26 months and median maintenance infliximab dose was 8.2 mg/kg. The median interval between infliximab infusions was 5.6 weeks. At one year, 64% achieved zero ocular inflammation, and 79% had zero inflammation or a two-step decline in inflammation. Topical glucocorticoids were discontinued in 69%, and 58% remained free of uveitis recurrence at one year. Visual acuity remained stable. Infliximab was discontinued in two children, one because of inefficacy and the other because of parental concern about potential side effects. No adverse events occurred. Sixteen children with chronic, noninfectious uveitis tolerated chronic methotrexate and infliximab therapy. Visual acuity remained stable, control of ocular inflammation improved, and reliance on topical glucocorticoids decreased. High infliximab doses and frequent dosing intervals were necessary to control uveitis.

Sustained Clinical Response and High Infliximab Survival in Psoriatic Arthritis Patients: A 3-year Long-Term Study

To investigate the efficacy, toxicity, and survival of infliximab in patients with psoriatic arthritis (PsA). Thirty-two patients with PsA, refractory to at least 2 disease-modifying antirheumatic drugs, were included in this prospective, open-label, uncontrolled study. All had active disease, defined as having a tender or swollen joint count > or =6, Psoriasis Area and Severity Index (PASI) scores > or =10, and erythrocyte sedimentation rate > or =28 mm Hg/h, or C-reactive protein > or =10 mg/L. The primary endpoints were the percentage of patients who achieved the Psoriatic Arthritis Response criteria (PsARC) and the improvement of PASI. Patients were treated with infliximab (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter for a period of 3 years. Data concerning infliximab efficacy, tolerability, concomitant therapy, adverse events, and drug discontinuation were recorded. The clinical response according to the American College of Rheumatology (ACR) criteria as well as the disease activity for 28 joint indices score (DAS-28) were also recorded. After the third year of treatment, PsARC was achieved by 23/32 of patients, PASI 70 by 24/32, and PASI 90 by 23/32. A significant improvement of ACR and DAS-28 was noted. Clinical improvement was associated with a reduction of acute phase reactants. Eight patients withdrew from the study primarily for acute allergic reactions. After the first year, infliximab survival was 84%, while after the second year, it was 75%, which was maintained throughout the third year of treatment. Infliximab was effective, safe, and well tolerated in patients with PsA. The clinical response was maintained for a period of 3 years with high infliximab survival.

Case Report: Evidence for Transplacental Transfer of Maternally Administered Infliximab to the Newborn

Control of Crohn's disease (CD) is important for conception and sustaining a pregnancy to term. Small series of infliximab use during pregnancy have reported favorable fetal and maternal outcomes. As a result of heightened maternal concern triggered by recent labeling changes, infliximab levels were measured in the newborn of a mother treated with infliximab. Serum and breast milk infliximab levels were measured by enzyme-linked immunosorbent assay. A 32-year-old woman with treatment-refractory CD continued infliximab therapy throughout pregnancy. Five infusions of infliximab, 10 mg/kg, the last one 2 weeks before delivery, successfully controlled her symptoms. Six weeks after delivery, the breast-fed infant's serum infliximab level was 39.5 microg/mL. Infliximab was not detected in the breast milk. Serial measurements revealed a continued slow decline of the infant's infliximab levels during the following 6 months, despite resumption of breast-feeding and subsequent retreatments of the mother with infliximab. Clinically significant infliximab levels were detected in the offspring. High infliximab levels in the serum of this infant are likely due to placental transfer, not breast-feeding. Similar to other maternally acquired antibodies, the half-life of infliximab appears prolonged in newborns. The true short-term and long-term implications of exposure to infliximab during the newborn period are unknown. Patients and physicians must be informed about in utero exposure to infliximab and potentially other therapeutic antibodies. The timing of infusions to minimize antibody transfer to the fetus might be an important strategic consideration when therapeutic antibodies are used in pregnancy.