Internal medicine journal · 2019
Infliximab and adalimumab concentrations and anti-drug antibodies in inflammatory bowel disease control using New Zealand assays.
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Barclay Murray L, Karim Shwan, Helms Esther T Johanna, Keating Paula E, Hock Barry, Stamp Lisa K, Schultz Michael
Аннотация
BACKGROUND: Therapeutic drug monitoring of anti-tumour necrosis factor (TNF) drugs and anti-drug antibodies (ADA) is now recommended in the treatment of inflammatory bowel disease. However, assay types and drug concentration thresholds are still debated.
AIM: To correlate inflammatory bowel disease activity in a New Zealand cohort with trough concentrations of infliximab and adalimumab, and ADA using locally developed competitive-binding enzyme-linked immunosorbent assays (ELISA) to establish threshold concentrations.
METHODS: Patients with ulcerative colitis (UC) and Crohn disease (CD) from Christchurch and Dunedin on anti-TNF drugs >12 weeks were enrolled. Trough blood samples were assayed for drug and ADA concentrations. Other data included quality of life, blood count, C-reactive protein, albumin, renal function and disease activity indices.
RESULTS: Of 103 patients, 53 were on infliximab (36 CD, 15 UC and 2 unclassified) and 50 adalimumab (48 CD and 2 UC). Median (range) infliximab and adalimumab concentrations were 10.5 (0-41) and 9.61 mg/L (0-30). CD remission, Crohn Disease Activity Index <150, correlated with infliximab and adalimumab concentration in CD (infliximab, P = 0.03; adalimumab, P = 0.04), with too few UC patients for analysis. Receiver operator curve analysis suggested a threshold value of 5.1 mg/L for distinguishing active disease from remission for infliximab and 7.3 mg/L for adalimumab in CD. Of 13 patients with infliximab <2 mg/L, 10 were ADA positive by homogeneous mobility shift assay (HMSA), including five with neutralising antibodies using ELISA. Of six with adalimumab <2 mg/L, three were ADA positive using HMSA, including one with neutralising antibodies.
CONCLUSION: Using the New Zealand ELISA assay, threshold concentrations of 5 mg/L for infliximab and 7 mg/L for adalimumab are suggested to aid dosing decisions, consistent with results internationally. Both neutralising (ELISA) and non-neutralising ADA (HMSA) are associated with low drug concentrations.
AIM: To correlate inflammatory bowel disease activity in a New Zealand cohort with trough concentrations of infliximab and adalimumab, and ADA using locally developed competitive-binding enzyme-linked immunosorbent assays (ELISA) to establish threshold concentrations.
METHODS: Patients with ulcerative colitis (UC) and Crohn disease (CD) from Christchurch and Dunedin on anti-TNF drugs >12 weeks were enrolled. Trough blood samples were assayed for drug and ADA concentrations. Other data included quality of life, blood count, C-reactive protein, albumin, renal function and disease activity indices.
RESULTS: Of 103 patients, 53 were on infliximab (36 CD, 15 UC and 2 unclassified) and 50 adalimumab (48 CD and 2 UC). Median (range) infliximab and adalimumab concentrations were 10.5 (0-41) and 9.61 mg/L (0-30). CD remission, Crohn Disease Activity Index <150, correlated with infliximab and adalimumab concentration in CD (infliximab, P = 0.03; adalimumab, P = 0.04), with too few UC patients for analysis. Receiver operator curve analysis suggested a threshold value of 5.1 mg/L for distinguishing active disease from remission for infliximab and 7.3 mg/L for adalimumab in CD. Of 13 patients with infliximab <2 mg/L, 10 were ADA positive by homogeneous mobility shift assay (HMSA), including five with neutralising antibodies using ELISA. Of six with adalimumab <2 mg/L, three were ADA positive using HMSA, including one with neutralising antibodies.
CONCLUSION: Using the New Zealand ELISA assay, threshold concentrations of 5 mg/L for infliximab and 7 mg/L for adalimumab are suggested to aid dosing decisions, consistent with results internationally. Both neutralising (ELISA) and non-neutralising ADA (HMSA) are associated with low drug concentrations.