Ustekinumab and Anti-Ustekinumab Antibody, DoseASSURE™ UST

Serum (preferred) or plasma

3mL

1mL (Note: this volume does not allow for repeat testing)

Red-top tube, gel-barrier tube, plasma EDTA tube, or plasma heparin tube

Allow a minimum clotting time of 30 to 60 minutes with serum separation within 2 hours of collection. Send serum in a plastic transport tube. To avoid delays in turnaround time when requesting multiple tests, please submit separate frozen specimens for each test requested.

Frozen (prefered) or refrigerated

Temperature Period Room Temperature 14 days Refrigerated 14 days Frozen 14 days Freeze/thaw cycles Stable x6

Provides ustekinumab drug concentration and anti‐ustekinumab antibodies in order to optimize treatment and facilitate clinical decision‐making. This assay may be helpful in any patients on ustekinumab therapy for Crohn's disease, psoriasis, or other autoimmune conditions.

Drug concentration should be interpreted with confirmation of specimen collection timing. Non‐trough concentrations may be misleading. Trough blood collection (just before or within 24 hrs. of next dose) is suitable because target ranges and therapeutic cut‐offs have been established in clinical studies using trough concentration. The drug half‐life should be taken into consideration when interpreting results from non‐perfect trough collections. Some primary non‐responders have inadequate clinical response despite adequate trough levels. As with other biologics, the optimal ustekinumab concentration depends upon patient‐specific factors including co‐morbidities, disease and desired therapeutic endpoint. Positive anti‐ustekinumab antibodies should be interpreted in the context of the concomitant free ustekinumab drug level.

Electrochemiluminescence immunoassay (ECLIA)

Ustekinumab drug level: <0.1 μg/mL • Result ≥0.1 μg/mL indicates detection of ustekinumab • In the presence of anti-ustekinumab antibodies, the ustekinumab drug level reflects the free, antibody-unbound fraction of ustekinumab in serum. Anti-ustekinumab antibody: <40 ng/mL • Result ≥40ng/mL indicates detection of anti-ustekinumab antibodies.

Drug Assay: The ustekinumab drug level typically reflects the antibody-unbound (the free fraction) of ustekinumab when serum anti-ustekinumab antibodies are present. In the absence of anti-infliximab antibodies, the ustekinumab drug level typically reflects the total ustekinumab concentration in serum. Anti-drug Antibody Assay: This anti-ustekinumab antibody assay is “drug-tolerant”, that is, the presence of serum ustekinumab does not impede the detection and quantitation of antiustekinumab antibodies. This anti-ustekinumab antibody assay is specific; antibodies against other biologic drugs do not cross-react with this assay. All positive anti-ustekinumab antibody results are verified by a confirmatory test. Both drug and anti-drug antibody assays have been developed and validated in accordance with FDA Guidance for Industry documents: Bioanalytical Method Validation (2013) and Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products (2016).

Adedokun O, et al. P-007 Exposure-Response to SC Ustekinumab in Moderate–Severe Crohn’s Disease: Results From the IM-UNITI Maintenance Study. Advances in IBD meeting, Orlando, FL, abstract. Oct 2017. Adedokun OJ, et al. Pharmacokinetics and Exposure-Response Relationships of Ustekinumab during IV Induction and SC Maintenance Treatment of Patients with Crohn’s Disease with UNITI-1, UNITI-2, and IM-UNITI Studies. Gastroenterology.2016;150(4):S408. Battat R, Kopylov U, Bessissow T, et al. Association Between Ustekinumab Trough Concentrations and Clinical, Biomarker, and Endoscopic Outcomes: Results in Patients with Crohn’s Disease. Clin Gastroenterol Hepatol. 2017 Sep;15(9):1427-1434.e2. PubMed 28365485 Chiu H, Chu TW, Cheng YP, Tsai TF. The Association Between Clinical Response to Ustekinumab and Immunogenicity to Ustekinumab and Prior Adalimumab. PLoS One. doi:10:1371/journal.pone.0142930. PubMed 26566272 Menting SP, van den Reek JM, Baerveldt EM, et al. The correlation of clinical efficacy, serum trough levels and antidrug antibodies in ustekinumab-treated patients with psoriasis in a clinical-practice setting. Br J Dermatol. 2015 Sep;173(3):855-857. PubMed 25865153