BACKGROUND: Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics. Secondary loss of response is frequently caused by the production of anti-drug antibodies, a well-known problem in IBD patients on biologic treatment. We present a case of IO-IBD treated with therapeutic drug monitoring (TDM)-guided high-dose anti-tumor necrosis factor therapy, in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.
METHODS: A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life, as well as relapsing perianal abscess and growth failure. Hypoalbuminemia, anemia, and elevated inflammatory markers were also present. Endoscopic assessment revealed skip lesions with deep colic ulcerations, inflammatory anal sub-stenosis, and deep fissures with persistent abscess. A diagnosis of IO-IBD Crohn-like was made. The patient was initially treated with oral steroids and fistulotomy. After the perianal abscess healed, adalimumab (ADA) was administered with concomitant gradual tapering of steroids. Clinical and biochemical steroid-free remission was achieved with good trough levels. After 3 mo, antibodies to ADA (ATA) were found with undetectable trough levels; therefore, we optimized the therapy schedule, first administering 10 mg weekly and subsequently up to 20 mg weekly (2.8 mg/kg/dose). After 2 mo of high-dose treatment, ATA disappeared, with concomitant high trough levels and stable clinical and biochemical remission of the disease.
CONCLUSIONS: TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production. This strategy could be a good alternative to combination therapy, especially in very young patients.

UNASSIGNED: To report the clinical course of patients with ocular inflammatory disease treated with adalimumab in whom anti-adalimumab antibodies (AAA) were detected.
UNASSIGNED: Single center case series.
UNASSIGNED: Eight patients with initial response to adalimumab developed a disease flare associated with positive AAA testing after 5 to 76 months of therapy. Six patients were receiving no concurrent antimetabolite therapy at the time of AAA diagnosis and four had a temporary lapse in adalimumab therapy prior to AAA discovery. AAA resulted in undetectable drug levels in five of the seven patients for whom data were available, and adalimumab was discontinued in six of the eight patients. Of two patients continued on adalimumab, one maintained detectable serum adalimumab despite AAA and one had a low AAA titer.
UNASSIGNED: For patients receiving adalimumab for ocular inflammatory disease, a disease flare in the setting of previously well-controlled disease should prompt consideration of AAA testing.

SHR-1222 is a humanized monoclonal antibody targeted to soluble sclerostin. To support the preclinical study of SHR-1222 in cynomolgus monkeys, a method for the detection of anti-drug antibodies is required.
A bridging immunogenicity method for the detection of anti-SHR-1222 antibodies was developed and validated. In the method, minimal required dilution, normalization factor and confirmatory cut point were 1:20, 4.35 and 10.45%, respectively. The method was successfully applied to evaluate a multiple-dose toxicity study in monkeys.
The proposed method allows for the detection of anti-SHR-1222 antibodies in preclinical studies and aids in the interpretation of pharmacokinetic changes in certain animals. The soluble targets interference on anti-drug antibody detection can be blocked or decreased by the therapeutic drug.

The advent of biopharmaceuticals (BPs) has led to significant improvements in the treatment of many chronic inflammatory diseases, and the number of BPs on the market and of diseases treated reflects their success. However, repetitive parenteral administration and intrinsic immunogenic properties of the drug can elicit an immune response, leading to production of anti-drug antibodies (ADA). This is a major limitation of the use of BPs and has to be taken into consideration in clinical practice and during drug development. With increasing knowledge about the immunogenicity of BPs and regular ADA testing in patients, we ensure optimized long-term treatment for the individual and thus optimal use of health care resources. This field has already been extensively investigated in the treatment of multiple sclerosis with IFN-β, but there is a clear need for consensus from academia, health care providers and the BP industry in managing ADA across all BPs and diseases.