High C-reactive protein in Crohn's disease patients predicts nonresponse to infliximab treatment

Magro, Fernando; Rodrigues‐Pinto, Eduardo; Santos-Antunes, João; Vilas-Boas, Filipe; Lopes, Susana; Nunes, Ana V. M.; Dias, Cláudia Camila; Macedo, Guilherme

doi:10.1016/j.crohns.2013.07.005

Cited by 79 publications

(56 citation statements)

References 41 publications

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“…For this description, we first used CRP as a biomarker. Indeed, CRP has been shown repeatedly to correlate well with sustained clinical response [8,17,18,20], and the relationship between infliximab concentration and CRP was previously investigated in RA [32,33]. Being an anti-TNF-α monoclonal antibody, adalimumab acts as a noncompetitive antagonist of TNF-α and does not act directly on CRP.…”

Section: Figurementioning

confidence: 99%

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Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

Ternant

Ducourau

Fuzibet

et al. 2015

Brit J Clinical Pharma

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AIMSThis study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokineticpharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA). METHODSAdalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model. The relationship between adalimumab concentration and C-reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated. RESULTSThirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd/F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day −1 (17%); first-order absorption rate (ka) = 0.28 day; CRP input (kin) = 22.0 mg l −1 day −1 (65%); adalimumab concentration leading to a 50% decrease in kin (C50) = 3.6 mg l −1 (88%); baseline DAS28 (DAS0) = 5.5 mg l −1 (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50) = 11.0 mg l −1 (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection.

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Section: Figurementioning

confidence: 99%

“…Given that normalization of CRP is associated with sustained clinical response, CRP may be considered as a clinically relevant biomarker [13,[17][18][19][20]. In addition, CRP is increased by TNF-α [21].…”

Section: Structural Modelsmentioning

confidence: 99%

Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

Ternant

Ducourau

Fuzibet

et al. 2015

Brit J Clinical Pharma

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“…22 Although a recent study found that higher pre-IFX CRP values were associated with a decreased likelihood of response to standard IFX dosing regimens, 23 it remains possible that patients with significant inflammatory burdens may only achieve symptom control with sufficiently high delivery of IFX that is not provided by standard dosing. IFX's intravenous administration makes it more practical to deliver these high doses than anti-TNF agents delivered subcutaneously.…”

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confidence: 99%

High-Dose Infliximab Therapy in Crohn’s Disease: Clinical Experience, Safety, and Efficacy

Hendler

Cohen

Colombel

et al. 2015

Journal of Crohn's and Colitis

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Baseline CRP values were significantly elevated in the group that responded at 1-16 weeks compared with nonresponders [22.0 vs 3.5 mg/L, p < 0.01]. HD IFX therapy was discontinued in 26% and 7.3% of patients for inadequate response and adverse events, respectively. Eleven cases of infection required hospitalization for a serious infection rate of 7.41 events per 100 patient-years. Conclusions: HD IFX therapy may benefit CD patients who have failed standard doses of IFX. HD IFX therapy may be associated with more serious adverse events compared with standard dosing. Baseline CRP value may predict clinical response to HD IFX.

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“…Patients with normal CRP level before the start of anti-TNF have significantly lower response rates [111][112][113]. In contrary, recent data suggest that very high CRP at baseline is predictive for primary non-response [114]. Florin et al found that 10% of patients with active disease had normal CRP levels, which makes CRP less useful in this situation [115].…”

Section: The Future Of Anti-tnf Therapymentioning

confidence: 93%

Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease

Pouillon

Bossuyt

Peyrin–Biroulet

2016

Expert Opinion on Biological Therapy

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High C-reactive protein in Crohn's disease patients predicts nonresponse to infliximab treatment

Abstract: CRP levels at week 14 were associated with SR in patients treated with IFX, independently of baseline CRP serum levels. High inflammatory burden at beginning of IFX treatment was correlated with a worse response.

Cited by 79 publications

References 41 publications

Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

High-Dose Infliximab Therapy in Crohn’s Disease: Clinical Experience, Safety, and Efficacy

Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease

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