Success and safety of high infliximab trough levels in inflammatory bowel disease.

OBJECTIVE: A prospective trial suggests target infliximab trough levels of 3-7 µg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce. AIM: To explore whether high infliximab trough levels (≥7 µg/mL) are more effective and still safe. MATERIAL AND METHODS: In this cohort study of 183 patients (109 Crohn's disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7 µg/mL during 420 patient-years. RESULTS: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66 mg/kg [30-257]; C-reactive protein 3 mg/L [3-3]) compared to trough levels below 7 µg/mL (fecal calprotectin 155 mg/kg [72-474]; C-reactive protein 3 mg/L [3-14.5]) (p < .001). High trough levels were superior also after excluding samples with trough levels <3 µg/mL from analysis. No differences in rates of infections were observed in quadrimesters with high trough levels (16/129 [12.4%]) compared to quadrimesters with trough levels <7 µg/mL (32/344 [9.3%]) (p = .32). Maintaining high trough levels resulted in 32% (interquartile range: 2-54%) increase of infliximab consumption. CONCLUSION: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.

Complete Revascularization and Survival in STEMI.

Background: Complete revascularization (CR) of ST-elevation myocardial infarction patients with multivessel coronary artery disease (MVD) has proven better regarding combined endpoints than incomplete revascularization (IR) in recent randomized control trials with no impact on survival. Objective: To retrospectively evaluate the impact of complete CR during the index hospitalization on survival in STEMI patients with MVD. Methods and results: We included all patients with MVD who underwent successful primary percutaneous coronary intervention for STEMI during their index hospitalization at the University Medical Centre Ljubljana, Slovenia (from 1 January 2009 to 3 April 2011). Coronary angiograms were reviewed for non-culprit coronary arteries (>2 mm in diameter and ≥50% stenosis) treated with percutaneous coronary intervention. Rates of all-cause and cardiovascular death were compared between 235 patients who underwent CR (N = 70) or IR (N = 165). After a median follow-up of 7.0 years (interquartile range 6.0-8.2) the CR group had lower rates of all-cause death (15.7% vs 35.8%, log-rank p = 0.003) and cardiovascular death (12.9% vs 23.6%, log-rank p = 0.046). Multivariable analysis with adjustment for confounders showed no benefit of CR for all-cause death (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.31-1.18, p = 0.139) or cardiovascular death (HR 0.80, 95% CI 0.37-1.72, p = 0.560). Age, elevated serum creatinine at inclusion, diabetes and cardiogenic shock at presentation were predictors of death. Conclusions: Patients with STEMI and MVD who underwent CR showed lower all-cause and cardiovascular death during follow-up than those who underwent IR. However, after adjustment for confounders, the real determinates of survival were independent of the revascularization method.

Correction: Complete Revascularization and Survival in STEMI.

[This corrects the article DOI: 10.5334/gh.1040.].

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease.

BACKGROUND: Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a safer but under-studied alternative. AIM: To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies. METHODS: We studied the clinical success and infliximab consumption of both strategies in 149 patients (94 Crohn's disease; 55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation. RESULTS: The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 µg/mL [IQR: 0.3-6.6] vs 5.0 µg/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. CONCLUSIONS: In this study, optimised infliximab monotherapy was as clinically effective as combination therapy but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.