Clinical Information

Guselkumab (Tremfya; Johnson and Johnson) is a fully human IgG1 lambda therapeutic monoclonal antibody used for the treatment of moderate to severe ulcerative colitis (UC) and Crohn disease (CD), as well as plaque psoriasis and psoriatic arthritis. Guselkumab targets interleukin (IL) 23A (IL-23p19) binding with high affinity to the p19 subunit and inhibiting further action.

Therapeutic drug monitoring (TDM) has become standard of care in the gastroenterology practice for biologic therapies used in CD and UC. TDM is routinely used to assess loss of response to therapy and proactively manage patients taking tumor necrosis factor inhibitors (eg, infliximab and adalimumab), alpha-4-beta7 integrins (vedolizumab), and IL-12/23 blockers (ustekinumab). With the approval of guselkumab for inflammatory bowel disease, TDM is expected to play an important role in managing loss of response to therapy and guide decision making for use of monotherapy or combination therapy.

The dosing of guselkumab varies according to the condition it is prescribed to treat. Patients with psoriatic arthritis and plaque psoriasis receive 100 mg subcutaneously at weeks 0 and 4 and every 8 weeks thereafter. Patients with UC are treated with 3 intravenous infusions of 200 mg each at weeks 0, 4, and 8, followed by 100 mg or 200 mg subcutaneously at week 12 and every 4 weeks thereafter. Mean steady state trough serum guselkumab concentration was 1.2 mcg/mL in both psoriatic arthritis and plaque psoriasis patients. UC mean steady-state trough concentrations were 1.4 and 10.7 mcg/mL, with 100 mg and 200 mg dose at maintenance stage, respectively. CD mean steady-state trough concentrations were 1.2 and 10.1 mcg/mL, with 100 mg and 200 mg dose at maintenance stage, respectively.

Guselkumab, like other therapeutic monoclonal antibodies, is immunogenic. Clinical trials have shown that antibodies-to-guselkumab occur at rates of about 6% to 9% for plaque psoriasis, 2% for psoriatic arthritis, 11% for UC, and 5% for CD. The presence of anti-drug antibodies against therapeutic monoclonal antibodies has been shown to impact clinical efficacy, either by accelerated clearance or by inhibition of target binding. Assessment for the presence of antibodies to guselkumab (ATG) may be important for the management of patients, especially for those individuals with sub-therapeutic trough concentrations of guselkumab. For those individuals demonstrating loss of response in the context of sub-therapeutic drug concentrations, the presence of ATG may indicate the need to transition to another treatment approach. In contrast, those individuals with sub-therapeutic drug concentrations in the absence of detectable ATG may benefit from dose escalation.