PO74 - Beyond weight-based dosing: high inter-individual variability and the role of Therapeutic Drug Monitoring (TDM) in the treatment of sarcoidosis with infliximab.
Martina Ceraudo (Italy)1; Giulia Zinni (Italy)1; Alessandro Dell'Edera (Italy)1; Riccardo Scarpa (Italy)1; Anna Palmieri (Italy)2; Marcello Rattazzi (Italy)1; Francesco Cinetto (Italy)1;
1 - Rare Diseases Referral Center, Internal Medicine 1, Department of Medicine (DIMED), AULSS2 Marca Trevigiana, Ca' Foncello Hospital, University of Padova, Padova, Italy.; 2 - Neurology Unit, AULSS2 Marca Trevigiana, Ca' Foncello Hospital, Treviso, Italy.;
Keywords: Therapeutic-Drug-Monitoring; Anti-drug-antibodies; Infliximab;
Select the theme: Controversies in Sarcoidosis Treatment
Type: Original Papers
Presentation: Poster Presentation

Introduction: Infliximab (IFX) is a key treatment for refractory sarcoidosis. However, its efficacy is often compromised by inter-individual pharmacokinetic variability and the development of anti-drug antibodies (ADA). Understanding what influence serum trough concentrations is essential for optimizing treatment.

Objectives: To identify clinical, anthropometric and biochemical predictors of IFX through concentrations in patients with sarcoidosis.

Materials and Methods: 25 patients on maintenance therapy were analysed. Correlations between clinical/anthropometric variables (BMI, mg/kg, CRP, albumin) and IFX levels were assessed using Spearman/Pearson coefficients. Subgroups (ADA+/-; BMI>25) were compared using Mann-Whitney U test. Inter-individual variability was quantified by Coefficient of Variation (CV%).

Results: The study population (68% male, median age 54 years [52-63]) showed median trough levels of 9.10 mcg/mL [5-13.85]. ADA-positivity (16% (N=4)) was associated with significantly lower drug levels (p=0.016); reduced adherence to DMARDs (75% vs 95.2%) and lower methotrexate doses (7.5 vs 12.5 mg/week, p=0.051). In ADA-negative patients (N=21), time since infusion was the only significant predictor of trough levels (rho = -0.520, p = 0.016). Significantly, weight-adjusted dosing (mg/kg) showed no correlation with actual serum concentrations (r = -0.085, p = 0.764), with a critical inter-individual variability (CV% 63.5%) even at fixed 8-week intervals (range 5.00–35.32 mcg/mL).. BMI, BSA, and renal function did not influence drug exposure; interestigly, overweight patients (BMI >25) showed numerically higher, non-significant trough levels (11.3 vs 7.6 mcg/mL; p=0.424). After log-transformation, a significant positive correlation emerged between serum albumin and drug retention (R=0.76, p=0.03). CRP showed a non-significant inverse trend with IFX levels (p=0.219). Pharmacokinetic stability was maintained regardless of treatment duration (p=0.228).

Conclusions: High inter-individual variability and the lack of correlation with body weight parameters suggest the ineffectiveness of the standard mg/kg regimen in sarcoidosis. These findings indicate that drug exposure is driven by individual immunological and metabolic factors, supporting a shift towards a personalized dosing strategy using Therapeutic Drug Monitoring (TDM).