Infliximab Trough Concentrations Research Articles

Infliximab Trough Concentrations >3 µg/mL Are Associated with Clinical Response in Crohn Disease

In a randomized, controlled trial, investigators compared 1-year remission rates in patients with inflammatory bowel disease (IBD) who underwent

Randomised clinical trial: deep remission in biologic and immunomodulator naïve patients with Crohn's disease - a SONIC post hoc analysis.

As treatment goals in Crohn's disease (CD) evolve, targets now include clinical remission (CR), mucosal healing (MH) and biological remission [C-reactive protein normalisation (CRPnorm )]. To evaluate the association of baseline factors and treatment with the achievement of different composite remission parameters at week 26. This post hoc analysis of the SONIC trial evaluated different composite remission measures at week 26 in a subgroup of patients with Crohn's disease activity index (CDAI) scores, CRP, and endoscopic data available at baseline and week 26 (N=188). Assessed composite remission measures were: CR (CDAI<150) and MH (absence of any mucosal ulcerations), previously referred to as 'deep remission;' and alternative composite endpoints: CR+CRPnorm (CRP<0.8mg/dL); CRPnorm +MH; and CR+CRPnorm +MH. Among analysed patients, 136/188 (72.3%) achieved CR and 90/188 (47.9%) achieved MH at week 26. All composite outcomes were significantly greater (Bonferroni significance level, P≤0.016) with combination therapy (i.e. infliximab and azathioprine; 52.3-63.6%) vs. azathioprine monotherapy (12.9-29.0%; p ≤ 0.005 for all comparisons). Composite remission rates including MH were significantly greater with combination therapy (52.3-56.9%) vs. infliximab (25.6-32.3%; P≤0.015 for all comparisons except CRPnorm +MH, P=0.017) and vs. azathioprine monotherapy (12.9-20.4%; P≤0.002 for all comparisons). Median serum trough infliximab concentrations among patients who achieved MH or CR+MH were greater when compared with those among patients who did not achieve MH (P=0.018) or CR+MH (P=0.053). Among the subgroup of patients with early Crohn's disease, MH alone or in combination with composite remission criteria significantly improved clinical outcomes of patients who received combination therapy. Combination therapy was more effective in achieving various composite remission measures vs. azathioprine or infliximab monotherapy. These data illustrate that 'deep remission' is achievable with combination therapy in a high percentage of patients with early Crohn's disease. ClinicalTrials.gov number: NCT00094458.

Long-Term Outcome of Patients With Crohn’s Disease Who Discontinued Infliximab Therapy Upon Clinical Remission

There are limited data on the effects of discontinuing infliximab therapy for Crohn's disease (CD). We investigated the long-term outcome of patients with CD who discontinued infliximab while in clinical remission, and searched for prognostic markers of continued remission after infliximab cessation. We performed a retrospective, single-center study of 100 patients with CD who discontinued infliximab upon achieving clinical remission; 84 patients continued immunomodulator therapy. Clinical and endoscopic data were retrieved from a medical database in Belgium, and patients were followed up through April 2013 (median, 9.7 y; interquartile range, 8-11.5 y). Sustained clinical remission (SCR) was defined as maintenance of disease remission, without escalation in medical therapy or CD-related surgeries, until the end of the follow-up period. We measured trough concentrations of infliximab, antibodies to microbial antigens, and circulating inflammatory markers in serum samples collected before treatment and at the time of infliximab discontinuation. At the end of the follow-up period, 52 patients had SCR. Univariate (log-rank) analysis associated SCR with patient age at diagnosis (≥25 y; P= .012) and disease duration (<1 y; P= .017). Among factors evaluated at the time of infliximab discontinuation, infliximab trough concentrations (<6 μg/mL; P= .031), complete mucosal healing (P= .046), and serum positivity for vascular cell adhesion molecule-1 (>0.67 μg/mL; P= .024) were associated with SCR. In multiple Cox proportional hazards regression analysis, only age at diagnosis of 25 years and older was associated independently with SCR (hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P= .04). In a large, real-life study, 52% of patients with CD who discontinued infliximab upon achieving clinical remission remained in SCR after a median period of approximately 10 years; Most patients remained on immunomodulator therapy. Although patients with CD have variable responses to infliximab, a subgroup achieved long-term remission after infliximab discontinuation.

The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

ObjectiveAlthough low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate...

A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn's disease

Patients with Crohn's disease (CD) may experience disease relapse on maintenance infliximab. Anti-drug antibodies likely contribute to loss of response, and serum infliximab levels likely correlate with efficacy. To prospectively evaluate the relationship between trough serum infliximab concentration and disease activity. Adult patients (N = 327) with a diagnosis of CD who had received at least five consecutive infliximab infusions and who planned to receive at least two additional infusions were enrolled. The Crohn's Disease Activity Index (CDAI), serum infliximab, C-reactive protein (CRP) and antibodies-to-infliximab (ATI) were assessed at baseline, week 4 and week 8. Receiver operating characteristic (ROC) analysis examined the relationship between infliximab concentrations and disease activity. The mean CDAI score, which decreased 1.05 points between infusions, did not correlate with the mean change in trough infliximab concentration (+0.39 μg/mL; r = 0.099, P = 0.083), but was associated with the mean change in CRP concentration (r = 0.19, P < 0.001). Trough infliximab concentrations below 2.8-4.6 μg/mL best predicted a ≥ 70 point increase in the CDAI between infusions, and those below 2.7-2.8 μg/mL best predicted CRP >5 mg/mL at the second infusion. ATI at either visit decreased the proportion of patients with therapeutic infliximab trough levels compared with patients who were ATI negative (17.5% vs. 77.3% at visit 1 and 13.8% vs. 75.6% at visit 3; P < 0.001 for both comparisons). This prospective study confirms the relationship between trough infliximab concentrations, inflammation and antibodies-to-infliximab. Infliximab trough concentrations below 3 μg/mL may increase the likelihood of symptoms and inflammation (ClinicalTrials.gov identifier: NCT00676988).

AB0278 Prolonging between-infusions interval is associated with positivity to anti-infliximab antibodies in rheumatoid arthritis and spondyloarthritis patients

ObjectivesTo analyze association between the presence of antibodies to infliximab (ATI) and the clinical and biological characteristics in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patientsMethodsSera from RA (n = 22)...

Early Infliximab Trough Levels Predict Remission at One Year in Pediatric IBD Patients

Among patients with IBD, detectable trough concentrations of infliximab (IFX) during maintenance dosing are associated with response to therapy. Moreover the presence of anti-infliximab antibodies (ATI) increases drug clearance and loss of response. It is unknown whether IFX and ATI levels at the completion of induction dosing predicts long term efficacy of maintenance therapy. We determined whether week 14 trough IFX levels (IFX14) and ATI levels (ATI14) were associated with week 54 outcomes in pediatric IBD patients. A prospective cohort of pediatric IBD patients receiving IFX were tested for IFX and ATI levels at both weeks 14 and 54 or at early termination. Primary non-responders (NR) were patients who stopped drug before week 14 and early terminators were patients who stopped drug between weeks 14-54. Primary outcome was week 54 clinical remission (CR): PCDAI <10 for Crohn's disease or partial Mayo <2 points and no sub-score >1 for ulcerative colitis and the absence of a dose or frequency intensification beyond 5 mg/kg q 8 weeks prior to week 54. Secondary outcomes were deep remission (DR): clinical remission with normal CRP, sustained durable remission (SDR): CR at every maintenance infusion (week 14-54) and week 54 IFX (IFX54) and ATI (ATI54) levels. Univariate analyses were used to determine associations between IFX14 and ATI14 and week 54 outcomes, as appropriate. Regression tree analysis was used to determine the optimal IFX14 cutoff level associated with remission. IFX and ATI ELISA testing were performed at Prometheus labs (San Diego, CA). A total of 38 patients (median age: 12.6 yrs.) were enrolled of whom 4 were primary NR. 2/4 primary NR had detectable ATI levels and 3/4 had undetectable IFX levels before week 14. Of the 34 who entered maintenance at week 14, 3 patients discontinued IFX prior to week 54. Of the remaining 31 patients, 20 met criteria for both clinical and deep remission and 14 for SDR. ATI were detected in 3/34 (8%) at week 14 and 7/34 (20%) at week 54 or at early termination. 4/7 patients developed ATI after week 14. Week 14 IFX trough level was associated with CR (P = 0.009), DR (P = 0.009) and SDR (p = 0.04). The optimal cut point for IFX trough level at week 14 to predict DR was 5.5 μmL (p = 0.01). IFX14 was associated with IFX54 (P = 0.02) and inversely associated with ATI54 (P = 0.003). ATI14 was associated with ATI54 (P = 0.004) and inversely associated with IFX54 (P = 0.06) but was not associated with any of the remission outcomes. Infliximab levels at week 14 are associated with clinical, deep and sustained durable remission at week 54, with a minimum trough level of 5.5 μg/mL strongly predictive of deep remission. Moreover, week 14 IFX trough levels correlate with both week 54 IFX and ATI levels. The presence of ATI at week 14 did not predict remission outcomes but did correlate with IFX and ATI levels at week 54. Assessment of infliximab levels at an early time point may be warranted to optimize dosing to maximize long term therapeutic benefit.

Therapeutic Drug Monitoring of Tumor Necrosis Factor Antagonists in Inflammatory Bowel Disease

Although tumor necrosis factor (TNF) antagonists have shown clear benefits over conventional treatments for inducing and maintaining clinical remission in both Crohn's disease and ulcerative colitis, a high proportion of patients lose response over time. Given the scarce alternative of treatments when treatment failure occurs, it is highly desirable to optimize both initial response and long-term continuation of TNF antagonists. One of the most well-characterized factors associated with loss of response to these agents is the development of immunogenicity, whereby the production of neutralizing antidrug antibodies accelerates drug clearance, leading to subtherapeutic drug concentrations and, ultimately, to treatment failure. However, other patient-related factors, such as sex and/or body size, and disease severity, including TNF burden and serum albumin concentration among others, also may influence the pharmacokinetics of these agents. Nevertheless, the evidence generated to date about these complex interactions is scarce, and further prospective studies evaluating their influence on the pharmacokinetics of TNF antagonists are needed. Drug adjustment empirically based on clinical symptoms often is inaccurate and may lead to suboptimal outcomes. Recent evidence shows that maintenance of an optimal therapeutic drug concentration is associated with improved clinical outcomes. Therefore, incorporation of therapeutic drug monitoring into clinical practice may allow clinicians to optimize treatment by maintaining effective drug concentrations over time.

Additional use of tacrolimus after switching to tocilizumab therapy in patients with primary lack of efficacy of infliximab therapy for rheumatoid arthritis

To the Editor, Recently, I reported, in Modern Rheumatology [1], on the characterization of the primary lack of efficacy of infliximab therapy and the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA). In that study, nine of the 24 patients (38%) who had started induction therapy with infliximab were found to be primary nonresponders. Based on their trough concentrations of infliximab, the primary nonresponders could be classified into two groups: rapid-clearance type (six cases) and residual type (three cases). Both types of nonresponders benefited from a switch to tocilizumab therapy; eight of the nine patients (89%) were successfully treated with tocilizumab. One patient in the rapid-clearance group (Table 1, case 1), however, failed to achieve a 20% improvement according to the American College of Rheumatology criteria (ACR20) at the end of 24 weeks of tocilizumab therapy. To date, no patients who responded well to tocilizumab therapy have relapsed. Since the publication of this earlier study, it has been pointed out by several rheumatologists that our reported success rate of tocilizumab therapy seemed to be higher than that based on their experience in daily practice. To address this concern, I present the clinical characteristics and therapeutic responses to tocilizumab of primary infliximab-nonresponders who have been newly identified since the last study. I also show the efficacy of the additional use of tacrolimus with tocilizumab therapy. Following the protocol of the previous study, I conducted induction therapy with infliximab (intravenous infusions of 3 mg/kg) in 12 patients. During the infliximab therapy, methotrexate (MTX) (4–8 mg/week) and folic acid (5 mg/week) were given concomitantly. One patient, case 5, was receiving low-dose prednisolone (5 mg/day) at the start of the infliximab therapy and continued to receive this medication concomitantly throughout the period of infliximab therapy. Four of the 12 patients (33%) were characterized by a primary lack of efficacy of infliximab through the induction therapy (Table 1, cases 2–5). In one of these patients (case 2), the trough serum concentration of infliximab at week 14 was below the therapeutic level (1 lg/ml) (rapid-clearance type). The other three patients (cases 3–5) maintained high enough serum infliximab levels to produce therapeutic effects (residual type). Case 2 received a dose escalation (addition of one vial), but he nevertheless showed undetectably low trough concentrations (less than 0.1 lg/ml). All primary nonresponders were switched from infliximab to tocilizumab therapy (intravenous infusion of 8 mg/kg every 4 weeks for 24 weeks). During this therapy, all patients except for case 3 continued to receive MTX (8 mg/week) and folic acid (5 mg/week) concomitantly. MTX was discontinued in case 3 because of hepatic toxicity. Case 5 continued to receive low-dose prednisolone. As shown in Table 2, two patients (cases 3 and 4) in the residual-type group achieved an ACR70 improvement and a good response as defined by the European League Against Rheumatism (EULAR) 24 weeks after making this switch. However, the other two patients (case 2, rapid-clearance type; case 5, residual type) were refractory to tocilizumab therapy; these patients S. Mori (&) Department of Rheumatology, Clinical Research Center for Rheumatic Disease, NHO Kumamoto Saishunsou National Hospital, 2659 Suya, Kohshi, Kumamoto 861-1196, Japan e-mail: moris@saisyunsou1.hosp.go.jp

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 μg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 μg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

Therapeutic Drug Monitoring of Infliximab in Spondyloarthritis: An Observational Open-Label Study

Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum concentration modifies physician decision and improves the control of disease activity in SpA. Thirty-two patients routinely treated with infliximab were included in an observational open-label study. On visit 1 (V1), according to disease activity, a preliminary therapeutic decision was selected among 4 therapeutic options (ie, decrease, increase, maintain the dosage of infliximab, or switch over for another treatment), and a blood sample was collected to measure infliximab trough serum concentration. The final therapeutic decision, based on both disease activity and infliximab serum concentration assessed at V1, was applied at the following infusion (V2). Clinical and biological evaluations were performed at V3 and V4 and compared with those at V1. The measurement of infliximab trough concentration modified the therapeutic decision for 10 patients (31%). For both patients with increased or decreased infliximab dosage at V2, median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was similar at V3 or V4 as compared with that at V1. However, a trend for an inverse relationship between infliximab serum concentrations and BASDAI was observed. Knowledge of infliximab trough concentration modified the therapeutic decision for SpA patients with predominantly axial symptoms but did not improve the control of disease activity as estimated by the BASDAI.

Colon salvage therapy for acute severe colitis: cyclosporine or infliximab?

Steroid-refractory acute severe colitis (ASC) poses a significant clinical challenge to both physicians and surgeons alike. This review highlights advances in management of these patients and the role of cyclosporine compared to infliximab. ASC affects 25% of patients with ulcerative colitis and is associated with measurable morbidity and mortality. Simple clinical and laboratory measures predict steroid refractoriness (such as stool frequency 3-8/day and C-reactive protein > 45 mg/l on day 3) and salvage therapy is appropriate at this stage. Preliminary data from randomized controlled trials suggest that early (7 and 98 day) response to cyclosporine and infliximab are comparable. Serum trough infliximab concentrations may correlate with outcome. Sequential therapy cannot usually be recommended due to limited response (70% colectomy at 3 years) and high rate of serious adverse events. Optimal salvage therapy will depend on detailed results of randomized controlled trials. Meanwhile, patients with ASC should receive either cyclosporine or infliximab before surgery as long as there is specialist expertise that allows early decision-making.

Primary lack of efficacy of infliximab therapy for rheumatoid arthritis: pharmacokinetic characterization and assessment of switching to tocilizumab

To characterize primary failure to infliximab and determine the efficacy of switching to tocilizumab in patients with rheumatoid arthritis (RA), we examined 24 RA patients who had started on infliximab therapy (3 mg/kg) as their first biological agent. Nine of the 24 patients were found to be primary nonresponders, defined as patients who had never achieved a 20% clinical improvement according to the American College of Rheumatology criteria (ACR20) during induction therapy. The remaining 15 patients had achieved an ACR20 response to infliximab, without any relapses, for at least the first 14 weeks. A higher baseline health assessment questionnaire score was markedly associated with primary unresponsiveness to infliximab (p = 0.0005). Six of the 9 primary nonresponders showed rapid clearance of infliximab: their trough concentrations of infliximab were under 1 μg/ml. The other 3 were classified as exhibiting the residual type of unresponsiveness, which was defined as unresponsiveness in patients who maintained serum infliximab levels above 1 μg/ml. Human antichimeric antibody was not detected in the rapid-clearance nonresponders. Dose escalation (5 mg/kg) was insufficiently effective. Primary nonresponders to infliximab were started on tocilizumab therapy (8 mg/kg, every 4 weeks), and their responses were assessed after 24 weeks of this second attempt at therapy. All the nonresponders, except for a single rapid-clearance patient, had achieved an ACR20 clinical improvement at the time of assessment. In conclusion, primary nonresponders to infliximab can be classified into rapid-clearance and residual types, based on their trough concentrations of infliximab, but both types of nonresponders seem to benefit from an early decision to discontinue infliximab therapy and switch to tocilizumab.

Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases.

IntroductionA proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab.MethodsAll patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATIpos if ATI were detected at least once during the follow-up period and ATIneg otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves.ResultsWe included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATIpos than ATIneg patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATIneg and ATIpos groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATIneg and ATIpos groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03).ConclusionsHigh concentrations of infliximab during treatment initiation reduce the development of ATI, and the absence of ATI may be associated with prolonged maintenance of infliximab. Thus, trough serum infliximab concentration should be monitored early in patients with rheumatic diseases.

Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis

Infliximab, an IgG1 monoclonal antibody (mab), has large inter-individual serum concentration variability. The objective was to determine the extent of the association of baseline albumin concentration and infliximab disposition in patient with ulcerative colitis. Data from 728 patients with ulcerative colitis from two clinical trials were analyzed to evaluate trends between infliximab pharmacokinetics and serum albumin, or liver or kidney function. Response in the placebo and treated groups were compared by baseline serum albumin concentrations (SAC) groups. Patients with higher SAC maintained higher infliximab concentrations, lower clearance, and longer half-life than patients with lower SAC. When analyzed by SAC quartiles, patients in the highest quartile had several-fold greater trough infliximab concentrations when compared with those in the lowest quartile. These observations were consistent in both studies and at different dose levels. Generally, clinical response in patients did not vary with SAC when the SAC was within the normal range, apparently because serum infliximab concentrations remained at therapeutic levels. However, patients with SAC lower than the normal laboratory reference range had much lower median serum infliximab concentrations and lower response rates compared with patients within normal SAC. Infliximab pharmacokinetics did not correlate with SGOT or creatinine clearance. It is hypothesized that the common rescue pathway for both albumin and IgG involving the neonatal Fc receptor may be responsible for the relationship between serum albumin and serum infliximab levels. Baseline albumin level may serve as a valuable and convenient measure of mab pharmacokinetic expectations in these patients.

Trough Infliximab Concentrations Predict Efficacy and Sustained Control of Disease Activity in Rheumatoid Arthritis

Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and is approved for refractory rheumatoid arthritis. We studied the association between infliximab concentration and long-term control of disease activity in patients with rheumatoid arthritis treated on a routine basis both in cross-sectional analysis and over the long term. Trough serum infliximab concentrations were measured in patients with rheumatoid arthritis receiving infliximab infusions during the period August to October 2006. Disease activity was assessed by the Disease Activity Score for 28 Joints (DAS28) and usual biologic markers. During a 42-week follow-up period, patients were classified into two groups: those continuing with the same or lower doses of infliximab (Group A = treatment success) and those who switched to another biopharmaceutical or required an increase in infliximab dose (Group B = treatment failure). Treatment maintenance for Group A was analyzed by categories of infliximab concentration at baseline and compared by the log rank test. In 28 patients, C-reactive protein and infliximab concentrations were inversely related. Infliximab concentration in patients with low disease activity (DAS28 3.2 or less) was higher than in those with persistent active disease (DAS28 greater than 3.2); median values were 3.26 and 0.16 mg/L, respectively (P < 0.01). Analysis after 42 weeks showed that patients in Group A had higher infliximab concentrations at baseline than those with treatment failure (P < 0.01). In rheumatoid arthritis, infliximab concentration is predictive of sustained efficacy with the same infliximab regimen and should be considered on a routine basis.

Infliximab concentration monitoring improves the control of disease activity in rheumatoid arthritis

IntroductionAdjustment of infliximab dosage for individuals may be useful in improving therapeutic response in rheumatoid arthritis (RA). Herein, we aimed to determine whether measurement of infliximab serum concentration modifies the therapeutic decision and improves the control of disease activity.MethodsRA patients routinely treated with infliximab were included in an observational open-label study. On visit 1 (V1), according to the disease activity, a preliminary therapeutic decision was selected among four therapeutic options and a blood sample was collected to measure trough serum infliximab concentration. The final therapeutic decision, based on both disease activity and serum infliximab concentration assessed at V1, was applied at the following infusion (V2). Clinical and biological evaluations were performed at V3 and V4 and compared with those at V1.ResultsWe included 24 patients. The final therapeutic decision differed from the preliminary decision for 12 patients (50%). For patients with increased infliximab dosage at V2, mean disease activity score for 28 joints (DAS28) decreased by about 20% at V3 or V4 as compared with V1 (P < 0.05). Decreased DAS28 was correlated with increased serum infliximab concentration (P < 0.02).ConclusionsThe measurement of infliximab trough concentration modifies the therapeutic decision for RA patients and helps improve control of disease activity. Therapeutic drug monitoring of infliximab in RA may be useful for individual dosage adjustment.