Respiratory medicine · 2025
Management of anti-drug antibodies against TNF-inhibitors in sarcoidosis patients.
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Otten Brady, Weinberg Danielle, Gregoski Mathew J, James W Ennis
Аннотация
RATIONALE: Tumor necrosis factor inhibitors (TNFi) infliximab and adalimumab are commonly used third-line treatments for chronic or refractory sarcoidosis. The utility of monitoring TNFi levels and anti-drug antibody (ADA) formation in sarcoidosis is unclear. This study aimed to identify factors associated with TNFi trough levels and ADA prevalence in real-world sarcoidosis patients.
METHODS: We included sarcoidosis patients treated with TNFi for ≥3 months at an academic specialty clinic who had trough drug and ADA levels assessed due to suboptimal therapeutic response. Associations between TNFi levels and dosing, patient characteristics, concomitant medications, and presence of ADAs were analyzed by univariate analysis.
RESULTS: 90 patients (median age 51 years, 66 % female, 60 % Black) met inclusion criteria (64 infliximab, 26 adalimumab). 66 % of patients were on at least 1 additional anti-sarcoidosis medication. The most common infliximab dose was 5 mg/kg every 6 weeks and adalimumab 40 mg weekly. Mean trough levels were 14.6ug/ml and 13.1ug/ml, respectively. ADAs were more prevalent in those on adalimumab (30.8 % vs 19.0 %). ADA presence was significantly associated with low infliximab (p < 0.001) and adalimumab levels (p < 0.001). For infliximab, concurrent use of second-line medications was associated with reduced prevalence of ADAs (8 % vs 38.9 %, p = 0.013) compared to patients on no additional immunosuppression.
DISCUSSION: This is the largest reported cohort assessing TNFi drug and ADA levels in sarcoidosis to date. Prevalence of ADAs was high, particularly against adalimumab. Second-line therapy may reduce ADA formation. Monitoring TNFi drug and ADA levels may aid clinicians in managing patients with a suboptimal response to therapy.
METHODS: We included sarcoidosis patients treated with TNFi for ≥3 months at an academic specialty clinic who had trough drug and ADA levels assessed due to suboptimal therapeutic response. Associations between TNFi levels and dosing, patient characteristics, concomitant medications, and presence of ADAs were analyzed by univariate analysis.
RESULTS: 90 patients (median age 51 years, 66 % female, 60 % Black) met inclusion criteria (64 infliximab, 26 adalimumab). 66 % of patients were on at least 1 additional anti-sarcoidosis medication. The most common infliximab dose was 5 mg/kg every 6 weeks and adalimumab 40 mg weekly. Mean trough levels were 14.6ug/ml and 13.1ug/ml, respectively. ADAs were more prevalent in those on adalimumab (30.8 % vs 19.0 %). ADA presence was significantly associated with low infliximab (p < 0.001) and adalimumab levels (p < 0.001). For infliximab, concurrent use of second-line medications was associated with reduced prevalence of ADAs (8 % vs 38.9 %, p = 0.013) compared to patients on no additional immunosuppression.
DISCUSSION: This is the largest reported cohort assessing TNFi drug and ADA levels in sarcoidosis to date. Prevalence of ADAs was high, particularly against adalimumab. Second-line therapy may reduce ADA formation. Monitoring TNFi drug and ADA levels may aid clinicians in managing patients with a suboptimal response to therapy.