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Results for “Infliximab”

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At least 19 recordsLinked to original sources

PubMed2006

Anti-infliximab antibodies in patients with rheumatoid arthritis who require higher doses of infliximab to achieve or maintain a clinical response.

OBJECTIVE: To determine whether the need to use doses of infliximab greater than 3 mg/kg every 8 weeks to achieve or maintain clinical response in patients with rheumatoid arthritis (RA) is associated with differences in baseline clinical characteristics or anti-infliximab antibodies. METHODS: Baseline clinical characteristics and anti-infliximab levels were evaluated retrospectively in a cohort of 51 consecutive patients with RA treated with infliximab at a single center. Patients were divided into 2 groups for comparison: Group 1 patients achieved and maintained clinical responses with infliximab 3 mg/kg every 8 weeks; Group 2 patients required higher doses. RESULTS: Thirty-two (63%) patients required infliximab dose escalation (Group 2). There were no statistically significant differences in baseline or clinical characteristics between Group 1 and Group 2 patients. Anti-infliximab antibodies occurred in 47% of Group 2 versus 27% of Group 1 patients, with higher anti-infliximab antibody concentrations in Group 2 patients (mean +/- SD: 18.3 +/- 8.9 g/ml vs 7.5 +/- 4.8 g/ml; p = 0.02). Patients who developed anti-infliximab antibodies were younger and receiving less prednisone at the time of infliximab initiation than patients who did not. CONCLUSION: Finding higher anti-infliximab antibody concentrations in patients who needed dose escalation of infliximab to achieve or maintain clinical responses with lower serum trough levels of infliximab suggests that development of anti-infliximab antibodies may reduce clinical efficacy of infliximab in some patients with RA.

Antibodies↗

PubMed2004

Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. RESULTS: After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders (median (interquartile range) 0.5 (0.2-2.2) v 3.6 (1.4-8.2) mg/l; p<0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment (Spearman rank correlation r(s) = -0.43, p<0.001). CONCLUSION: Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing intervals.

Adult↗

PubMed2006

Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis.

BACKGROUND: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. OBJECTIVE: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. METHODS: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. RESULTS: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. CONCLUSION: Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.

Adult↗

PubMed2005

Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).

OBJECTIVE: To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). METHODS: One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. RESULTS: The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. CONCLUSION: Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.

Adult↗

PubMed2005

Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

Antibodies, Monoclonal↗

PubMed2006

Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects.

OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.

Adult↗

PubMed2004

Investigation of the prognostic value of TNF-alpha gene polymorphism among patients treated with infliximab, and the effects of infliximab therapy on TNF-alpha production and apoptosis.

OBJECTIVES: Infliximab, a chimeric anti-tumor necrosis factor (TNF) antibody, is highly effective for the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). Our experiments focused on RA and CD patients receiving infliximab. Since cytokine production is largely determined by genetic factors, the promoter polymorphisms of TNF-alpha were examined among these patients. Additionally, the changes caused by infliximab in the TNF-alpha-producing ability and apoptosis of peripheral blood mononuclear cells (PBMCs) were investigated. METHODS: The TNF-alpha genotypes were analyzed by PCR-RFLP. The in vitro TNF-alpha production of the PBMCs was detected by flow cytometric analysis. The TNF-alpha concentration in the supernatant was measured by bioassay. Apoptosis was detected by annexin V-fluorescein isothiocyanate labeling. RESULTS AND CONCLUSIONS: 8 of the 12 nonresponder patients carried the TNF A allele associated with high TNF-alpha production. We suggest that the determination of TNF polymorphism may help identify more suitable candidates for infliximab treatment. Although in vitro infliximab treatment for 48 h resulted in significant (44.2 +/- 1.17%) apoptosis in PBMCs, in ex vivo samples from RA patients who received infliximab, apoptosis was only 13.3 +/- 1.6%. Furthermore, infliximab did not result in irreversible inhibition of the TNF-alpha-producing ability or in the significant apoptosis of PBMCs.

Alleles↗

PubMed2005

Methotrexate dosage reduction in patients with rheumatoid arthritis beginning therapy with infliximab: the Infliximab Rheumatoid Arthritis Methotrexate Tapering (iRAMT) trial.

OBJECTIVE: Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered. METHODS: Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure. RESULTS: Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54. CONCLUSION: Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.

Adolescent↗

PubMed2006

[Efficacy of infliximab in patients with moderate and severe psoriasis treated with infliximab (Remicade)].

BACKGROUND: Psoriasis has a moderate or severe course in 25% of patients, requiring systemic therapy that is not always successful. Infliximab is a human-murine monoclonal anti tumor necrosis alpha (TNF-alpha) antibody. This mediator has a role in the pathogenesis of psoriasis. AIM: To evaluate the use of infliximab in psoriatic patients resistant to conventional therapies. MATERIAL AND METHODS: An open prospective study including eight patients with extensive plaque or erythrodermic psoriasis. They were treated with infliximab 5 mg/kg/dose on weeks 0,2 and 6. Patients were evaluated every 2 weeks for a median lapse of 50.1 weeks. Physical examination, PASI scores (Psoriasis Area Severity Index) and a photographic control, were done in each visit. RESULTS: All the patients responded in the first 10 weeks of follow-up. The mean reduction in PASI score was 86.6%. Six patients received fourth infusion of infliximab at 37.3 weeks, on average. The most common adverse events were pruritus and headache. CONCLUSIONS: This group of patients with extensive plaque or erythrodermic psoriasis resistant to conventional therapies, had a good response to infliximab.

Adult↗

PubMed2005

Infliximab in Hispanics: characterization of response to infliximab in an ethnic minority with Crohn's disease.

PURPOSE: The incidence and prevalence of Crohn's disease (CD) varies geographically and with racial/ ethnic background. The highest frequency of occurrence is in North America and Northern Europe. Incidence is highest among Caucasians, lower in blacks and Hispanics, and lowest in Asians. However in the mid-1980s and 1990s, the incidence and prevalence increased in continental Europe, the Middle East, the Pacific Rim, Africa, and Latin America. An increase in the incidence of CD has been noted in Puerto Rico, although our population differs genetically from other described CD populations. A study in our population showed lower prevalence of ASCA and no NOD2 in our CD patients. Infliximab, a TNFa antibody, is effective in refractory inflammatory CD and in fistulizing disease. Since limited data exists regarding CD in Hispanics, the fastest growing minority group in the United States, we designed this retrospective study with patients treated with infliximab at our institution. We wanted to determine if the response to infliximab in genetically admixed Hispanics differed from that previously reported. METHODS: Baseline characteristics, infusion related information and clinical response was abstracted from medical records. Clinical response was classified as complete response, partial response, and nonresponse. RESULTS: The study included 15 patients treated for refractory inflammatory disease, 9 for fistulizing disease, and 11 for both. The positive response rate was 83%(29/35) and the non response rate was 17%(6/35). Overall the patients with complete, partial, and no response were 13/35(37%), 16/35(46%), and 6/ 35(17%), respectively. No statistically significant association was found between response and disease location. Significant association was found between response and fistula type (p = 0.02). Steroid withdrawal was possible in 21/31 patients (68%). In terms of safety, 9/35 patients (26 %) suffered an adverse reaction, 4 patients required therapy discontinuation. CONCLUSION: This study suggests that infliximab has similar global response, allowance of steroid withdrawal and safety in Hispanics as in other populations. Ethnicity does not seem to influence response rate to infliximab.

Adolescent↗

PubMedDate not supplied

Repeated infusions of low-dose infliximab plus methotrexate in psoriatic arthritis: immediate benefits are not maintained after discontinuation of infliximab.

OBJECTIVE: To assess the long-term efficacy and tolerability of a therapy consisting of infliximab at low dosage plus methotrexate in patients with psoriatic arthritis (PsA). As a second objective, we assessed whether the improvement obtained after 54 weeks of infliximab could be maintained with methotrexate alone. METHODS: A group of 26 patients with peripheral PsA resistant to various DMARDs were treated with infliximab + methotrexate for 54 weeks. RESULTS: The clinical response after the induction period was constant and progressive, with a high percentage of patients achieving an ACR50 response. The ESR and CRP values also declined continuously and gradually, but only CRP returned to normal values. During the follow-up period after 54 weeks, infliximab was stopped and the improvement obtained lasted for 2-6 months. The secondary end point was not achieved, and an extension period was designed. Results at 78 weeks are presented. CONCLUSIONS: Open questions for treating patients with infliximab and methotrexate are the schedule and the length of the administration and how to preserve the improvement obtained after the drug discontinuation.

Adult↗

PubMed2001

Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of Crohn's disease. Infliximab, a chimeric antibody against TNF-alpha, has been shown in controlled clinical trials to be effective in two-thirds of patients with refractory or fistulating Crohn's disease. The factors that determine a clinical response in some patients but not others are unknown. AIMS: To document the early Australian experience with infliximab treatment for Crohn's disease and to identify factors that may determine a beneficial clinical response. METHODS: Gastroenterologists known to have used infliximab for Crohn's disease according to a compassionate use protocol were asked to complete a spreadsheet that included demographic information, Crohn's disease site, severity, other medical or surgical treatments and a global clinical assessment of Crohn's disease outcome, judged by participating physicians as complete and sustained (remission for the duration of the study), complete but unsustained (remission at 4 weeks but not for the whole study) or partial clinical improvement (sustained or unsustained). RESULTS: Fifty-seven patients were able to be evaluated, with a median follow-up time of 16.4 (4-70) weeks, including 23 patients with fistulae. There were 21 adverse events, including four serious events. Fifty-one patients (89%) had a positive clinical response for a median duration (range) of 11 (2-70) weeks. Thirty patients (52%) had a remission at 4 weeks, 10 of whom had remission for longer than 12 weeks. Forty-two per cent of fistulae closed. Sustained remission (P = 0.065), remission at 4 weeks (P = 0.033) and a positive clinical response of any sort (P = 0.004) were more likely in patients on immunosuppressive therapy, despite there being more smokers in this group. CONCLUSION: This review of the first Australian experience with infliximab corroborates the reported speed and efficacy of this treatment for Crohn's disease. The excellent response appears enhanced by the concomitant use of conventional steroid-sparing immunosuppressive therapy.

Adolescent↗

PubMed2005

Infliximab-induced headache and infliximab-induced meningitis: two ends of the same spectrum?

This report describes a case of aseptic meningitis induced by the tumor necrosis factor-alpha inhibitor infliximab. The patient, a 51-year-old female, was being treated for Crohn's disease. After an infliximab infusion, she had headache, fever, arthralgia, myalgia, and meningismus. Cerebrospinal fluid analysis was remarkable for a neutrophilic pleocytosis and elevated protein. Other potential causes of meningitis were excluded. Her symptoms completely resolved within 24 hours of presentation. Because infliximab commonly causes headache and is very immunogenic, we infer that infliximab-induced meningitis is immune-mediated and underrecognized. Potential risk factors and means for minimizing its occurrence are offered.

Antibodies, Monoclonal↗

PubMed2005

DAS28 best reflects the physician's clinical judgment of response to infliximab therapy in rheumatoid arthritis patients: validation of the DAS28 score in patients under infliximab treatment.

This study is based on an expanded access program in which 511 patients suffering from active refractory rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab (3 mg/kg+methotrexate (MTX)) at weeks 0, 2, 6 and every 8 weeks thereafter. At week 22, 474 patients were still in follow-up, of whom 102 (21.5%), who were not optimally responding to treatment, received a dose increase from week 30 onward. We aimed to build a model to discriminate the decision to give a dose increase. This decision was based on the treating rheumatologist's clinical judgment and therefore can be considered as a clinical measure of insufficient response. Different single and composite measures at weeks 0, 6, 14 and 22, and their differences over time were taken into account for the model building. Ranking of the continuous variables based on areas under the curve of receiver-operating characteristic (ROC) curve analysis, displayed the momentary DAS28 (Disease Activity Score including a 28-joint count) as the most important discriminating variable. Subsequently, we proved that the response scores and the changes over time were less important than the momentary evaluations to discriminate the physician's decision. The final model we thus obtained was a model with only slightly better discriminative characteristics than the DAS28. Finally, we fitted a discriminant function using the single variables of the DAS28. This displayed similar scores and coefficients as the DAS28. In conclusion, we evaluated different variables and models to discriminate the treating rheumatologist's decision to increase the dose of infliximab (+MTX), which indicates an insufficient response to infliximab at 3 mg/kg in patients with RA. We proved that the momentary DAS28 score correlates best with this decision and demonstrated the robustness of the score and the coefficients of the DAS28 in a cohort of RA patients under infliximab therapy.

Antibodies, Monoclonal↗

PubMed2005

Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: a role for scintigraphy with 99mTc-infliximab.

Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and Behcet's disease. We used intraarticular infliximab to treat resistant knee monarthritis in a patient with spondylarthropathy. Clinical and laboratory improvement was associated with improvement in scintigraphic findings. This approach is less expensive than intravenous administration of infliximab. We suggest that selection of candidates for this innovative therapy should be guided by anti-tumor necrosis factor alpha scintigraphy.

Adult↗

PubMed2005

Anaphylactic reaction to infliximab in two rheumatoid arthritis patients who had previously received infliximab and resumed.

Here we report on two cases of anaphylactic reaction following infliximab infusion in patients with active rheumatoid arthritis (RA). Both individuals had received infliximab treatment during a clinical trial approximately 2 years prior to further therapy; subsequent infusion of this agent led to anaphylactic reactions in both cases. In light of these findings, we recommend that future treatments with infliximab in RA patients who have previously received this agent should be carefully monitored.

Journal Article↗

PubMed2006

Successful treatment of life-threatening intestinal ulcer in Behçet's disease with infliximab: rapid healing of Behçet's ulcer with infliximab.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disorder characterized predominantly by recurrent orogenital ulcers, skin involvement, and uveitis. Recurrent mucocutaneous lesions may be the only symptom in mild cases, but ocular, gastrointestinal, and central nervous system involvement may occur in severe cases. We report in this study the successful treatment with infliximab of severe life-threatening GI bleeding caused by an ileal ulcer in a patient with Behçet's disease. Antitumor necrosis factor (TNF) therapy could be an emergency therapeutic option in patients with massively bleeding Behçet's disease and unstable patients or those with acute bleeding with other TNF-alpha-mediated autoimmune diseases. Another option for anti-TNF therapy could be as bridging management between conservative and surgical treatment.

Adult↗

PubMed2005

Formation, distribution, and elimination of infliximab and anti-infliximab immune complexes in cynomolgus monkeys.

Infliximab (IFX) is a chimeric IgG1 monoclonal antibody specific for human tumor necrosis factor-alpha that is approved in the United States and Europe for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Approximately 10% of RA and CD patients receiving maintenance treatment with IFX will develop antibodies to IFX. The objective of this study was to develop a model to assess the in vivo formation, distribution, and elimination of immune complexes resulting from a low-level immune response in the presence of the excess concentration of a therapeutic antigen. In this model, cynomolgus monkeys were treated with a single intravenous injection of IFX, followed by injection of either radiolabeled, purified monkey anti-IFX IgG antibody (n = 3, test group) or radiolabeled monkey, nonimmune IgG (n = 3, control group). High-performance liquid chromatography analysis of collected sera revealed a rapid formation of immune complexes comprised of IFX and radiolabeled anti-IFX IgG antibody immune complexes. The terminal half-life of the anti-IFX IgG antibody immune complex was approximately 38 h compared with 86 h for the nonimmune antibody. However, the pharmacokinetic profile of IFX, although slightly lower in concentration over time for the test group, was not notably different relative to the control group. There were no macroscopic or microscopic histological findings in either treatment group. These data confirm that immune complexes between IFX and anti-IFX IgG antibodies can form in vivo and that these immune complexes are eliminated more rapidly than nonimmune antibodies in the presence of excess IFX.

Animals↗