Psoriasis and psoriasiform skin lesions in patients with Inflammatory Bowel Disease treated with infliximab: a pharmacokinetic analysis

Abstract Background Anti-TNF agents are used to treat a variety of autoimmune conditions, including psoriasis. Paradoxically, new onset of psoriasis or psoriasiform skin lesions (PPSL) can occur in patients treated with these agents. We report a case series of patients featuring PPSL induced by infliximab (IFX) with pharmacokinetic and fecal calprotectin (Fc) correlation. Methods One hundred and thirty-five consecutive patients with Inflammatory Bowel Disease under proactive therapeutic drug monitoring (TDM) with IFX were evaluated for PPSL. Results Fifteen patients (11.1%) developed PPSL, 12 females (80%), with median age at diagnosis of 52.0 years (38-63). At the onset of PPSL, 6 patients were on 10 mg/kg every 6 weeks, 5 patients on 5 mg/kg every 8 weeks, 2 patients on 10 mg/kg every 4 weeks, 1 patient on 10 mg/kg every 8 weeks, and 1 patent on 5 mg/kg every 6 weeks. In patients with PPSL, IFX trough levels (IFXTL) significantly increased before and after the advent of PPSL: 6.18 µg/mL (3.28-9.91) vs 9.20 µg/mL (5.89-13.91), P= 0.001. At the time of PPSL, all but 2 patients were in Fc remission (< 250 µg/g), median 41 µg/g (30-103). Seven patients improved with topic therapy and 8 patients (53.3%) discontinued IFX (3 switched to ustekinumab) all of which improved. Compared with the overall cohort, IFXTL were higher in patients with PPSL: 7.27 µg/mL (4.02-10.86) vs 6.26 µg/mL (3.37-9.14), P= 0.023. In multivariate regression analysis, female gender [OR 4.84 95%CI (1.23-19.00), P= 0.024], and any IFXTL≥ 10 µg/mL [OR 5.66 95%CI (1.40-22.87), P= 0.015] were independent predictors of developing PPSL. Conclusion Most patients with PPSL presented high IFXTL and low Fc. We hypothesize that high concentrations of IFX in the setting of deep remission may signal aberrant pro-inflammatory pathways potentially responsible for PPSL.