Clinical Information

Risankizumab (Skyrizi, AbbVie) is a humanized IgG1 kappa therapeutic monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn disease.(1,2) Risankizumab targets interleukin 23A (IL-23p19), binding with high affinity to the p19 subunit and inhibiting further action.(3)

Therapeutic drug monitoring (TDM) has become standard-of-care for biologic therapies used in inflammatory bowel disease (IBD). In this context, TDM requires both quantitation of the therapeutic monoclonal antibody and assessment for the presence of anti-drug antibodies. Accurate interpretation of drug quantitation requires knowledge regarding patient diagnosis, drug dosage, and treatment schedule. Patients with plaque psoriasis or psoriatic arthritis are treated with 150 mg subcutaneously at weeks 0, 4, and every 12 weeks thereafter. The steady state maximum concentration (Cmax) and trough concentration (Ctrough) are estimated to be 12 mcg/mL and 2 mcg/mL, respectively. Patients with Crohn disease are treated with 600 mg intravenously at weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneously at week 12 and every 8 weeks thereafter. During induction weeks 8 through 12, the median Cmax is estimated to be 156 mcg/mL, and the Ctrough is estimated to be 38.8 mcg/mL, according to the drug package insert. Steady state is achieved at 28 weeks after starting treatment in the dosing regimen for Crohn disease. Median Cmax and Ctrough concentrations measured during weeks 40 through 48 of maintenance phase (or weeks 52-60 from start of treatment) are estimated to be 14.0 mcg/mL and 4.1 mcg/mL, respectively, for 180 mg dose or 28.0 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg dose.(4)

The other important aspect of TDM for therapeutic monoclonal antibodies is detection of anti-drug antibodies. Similar to other therapeutic antibodies, risankizumab is immunogenic. Development of antibodies to risankizumab (ATRs) may increase drug clearance in treated patients and/or neutralize the drug effect, thereby potentially contributing to loss-of-response. Clinical trials have shown ATRs occur at rates of about 24% for plaque psoriasis, 12% for psoriatic arthritis, and 3.4% for Crohn disease.

In the context of limited initial response or loss-of-response over time to risankizumab, measurement of circulating drug concentrations and assessment for ATRs can help to guide patient management. For example, patients with low risankizumab trough concentrations in the absence of ATRs might benefit from dose escalation in an attempt to increase the circulating amount of the drug. In contrast, for patients with low drug concentrations and a detectable ATR, transition to a new drug therapy may be indicated.