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Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation.

ABSTRACT: Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62?g/mL vs. 1.15?g/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3?g/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250?g/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

SUBMITTER: Magro F

PROVIDER: S-EPMC5514398 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation.

Magro Fernando F Afonso Joana J Lopes Susana S Coelho Rosa R Gonçalves Raquel R Caldeira Paulo P Lago Paula P de Sousa Helena Tavares HT Ramos Jaime J Gonçalves Ana Rita AR Ministro Paula P Rosa Isadora I Vieira Ana Isabel AI Andrade Patrícia P Soares João-Bruno JB Carvalho Diana D Sousa Paula P Meira Tânia T Lopes Joanne J Moleiro Joana J Dias Cláudia Camila CC Falcão Amílcar A Geboes Karel K Carneiro Fatima F

EBioMedicine 20170607

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and ...[more]

PMID: 28629912

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Project description:BACKGROUND AND AIMS:Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. METHODS:In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ?35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. RESULTS:A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p?=?0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission (p?=?0.04, p?<?0.001, and p?=?0.01, respectively). In a multivariate analysis, a PUCAI ?65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure (p?=?0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p?=?0.05). Kaplan-Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1-15.6%) in children with severe UC and 3.92% (95% CI 2.9-10.8%) in patients with moderate UC (logrank test p?=?0.06). CONCLUSIONS:Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.

Dataset Information

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation.

Publications

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation.

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