Detection of adalimumab and antibodies to adalimumab using a homogeneous mobility shift assay.

OBJECTIVE: In 2013 a novel commercial test was launched (Anser 1 ADA test) for the assay of serum adalimumab (ADL) and antibodies to adalimumab (ATA). This study aims to understand clinical practice patterns used with ADL in a real-world cross-sectional population. METHODS: Wilcoxon rank sum test, and linear and logistic regression methods were applied in the statistical analysis to test hypotheses. The study design was observational and uncontrolled. RESULTS: Of a total of 14,239 tests conducted, 5509 had information available that pertained to reasons for ordering, of which disease monitoring (46.9%) was the most common. Median serum ADL level with standard maintenance dosing (40 mg, biweekly) was 8.8 µg/mL (n = 2901). A five-fold decrease in median serum ADL levels occurred with very low ATA titers (1.7-3 U/mL, p < .0001). Serum ADL levels decreased further with ATA >7 U/mL (p < .0001). A total of 16.5% of patients were ATA positive, of whom 61.9% had low ATA (1.7-7 U/mL); 87.9% of ATA-positive patients had serum ADL levels ≤4.4 µg/mL. Expression of inflammatory markers significantly increased with high ATA (>7 U/mL). An inverse relationship between ADL and ATA was observed (R2: 0.49), and 4.1 µg/mL was identified as a cut-off that may segregate ATA-positive patients. CONCLUSION: In this real-world cross-sectional population, serum ADL levels decreased with increasing ATA titers, with low ATA titers (≤7 U/mL) significantly reducing serum ADL compared to ATA-negative samples. Expression of inflammatory markers significantly increased at higher ATA titers (>7 U/mL). These findings highlight the clinical importance of monitoring patients for drug levels and anti-drug antibody titers.

Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM.

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015. RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. CONCLUSIONS: HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients.