Introduction
Therapeutic monitoring of infliximab (INF) correlates with improved therapeutic outcomes in inflammatory bowel diseases (IBD).
Aims & Methods
The aim of this cross-sectional study was to assess the relationship between serum INF trough levels (TLs) and positive therapeutic outcomes in patients with ulcerative colitis (UC) and Crohn’s disease (CD) in a Greek population. The relationship between adverse events (AEs) and the existence of anti-infliximab antibodies (ADAs) was also investigated. Consecutive adult patients with IBD treated with intravenous INF at maintenance phase in a Greek tertiary centre were included. Investigated therapeutic outcomes included sustained clinical remission (CR), steroid-free clinical remission (SFCR), biomarker remission (CRP <5mg/L, BR) and combined (steroid-free clinical and biochemical) remission (SFCBR). Infliximab TLs and ADAs were assessed using ELISA-based assays.
Results
A total of 77 patients were enrolled (62.3% male, mean age 44 years), 48 (62.3%) with CD, 26 (33.8%) with UC and 3 (3.9%) with unclassified colitis. The mean disease duration was 11.7±8.4 years, while the mean duration of INF infusion was 5.1±4.6 years. Forty-seven (61%) patients had undergone treatment escalation, with a further dose escalation in 7 (9.1%) patients. Concomitant combined therapy was given in 13 (16.8%) patients, 4 (5.2%) of them were receiving azathioprine and 9 (11.7%) corticosteroids. Mean INF-TLs were 7.2±4.9 μg/mL and only correlated with treatment escalation (9.7 vs 3.6 μg/mL, p<0.001). Sixty-eight (88.3%) patients had CR, 62 (80.5%) had SFCR, 48 (62.3%) had BR and 43 (55.8%) had SFCBR. Compared to non-responders, mean INF-TLs were numerically higher, although not significantly different, in CR (7.5 vs 5.5 μg/mL, p=0.254), SFCR (7.3 vs 6.9 μg/mL, p=0.761), BR (7.4 vs 6.9 μg/mL, p=0.707) or SFCBR (7.7 vs 6.6 μg/mL, p=0.349).
In a subgroup analysis, among patients without treatment escalation, 27 (90%) had CR, 25 (83.3%) had SFCR, 22 (73.3%) had BR and 19 (63.3%) had SFCBR. Mean INF-TLs were significantly increased among patients with BR (4.2 vs 0.8 μg/mL, p=0.020) and SFCBR (4.3 vs 1.5 μg/mL, p=0.035). In ROC analysis, TLs could significantly predict (p=0.016) with a good accuracy (AUC 0.768, 95% Cl: 0.584=0.952) patients with SFCBR, with an optimal TL cut-off at 3.4 μg/mL. Among patients with treatment escalation, 41 (87.2%) had CR, 37 (78.7%) had SFCR, 26 (55.3%) had BR and 24 (51.1%) had SFCBR. In ROC analysis, TLs could significantly predict (p=0.018) with a fair accuracy (AUC 0.653, 95% CI: 0.527=0.755) patients with SFCBR, with an optimal TL cut-off at 11 μg/mL.
Twenty patients had TLs <1 μg/mL, of whom 10 had positive ADAs. Among them, 9 showed combined remission, 4 of whom had positive ADAs. Among 21 (27.3%) patients with reported AEs, 8 (10.4%) had an allergic reaction, which was attributed to INF. Allergic reactions had a tendency of correlation with ADA existence, as 4/5 patients with allergic reaction and TLs <1 μg/mL had positive ADAs, while 4/10 patients with positive ADAs reported allergic reaction, compared to 1/10 patients with negative antibodies (p=0.152).
Conclusion
Infliximab TLs correlate with treatment escalation. Higher TLs appear to result in favourable therapeutic outcomes. It is suggested that patients undergoing treatment escalation could benefit from higher INF-TLs in the achievement of favourable outcomes.