IL-12/IL-23 Inhibitor
Ustekinumab is a monoclonal antibody that binds the p40 subunit shared by IL-12 and IL-23, blocking their ability to bind receptors. IL-12 and IL-23 play a role in activating naïve T cells to become TH1 or TH17 cells, respectively.
Efficacy and Safety
Clinical trials demonstrate long-term efficacy of ustekinumab, which was approved for psoriasis in 2009, PsA in 2013, and later pediatric psoriasis (≥12 years of age) in 2017. Dosing is listed in Table 2.
Laboratory abnormalities did not arise in trials. Periodic tuberculosis screening is required. Prospective data over 5 years showed very low rates of adverse events (AEs), serious infections, malignancies, and major adverse cardiovascular events.20 Ustekinumab did not worsen or improve demyelinating disease and appears safe in this population.
Patient Selection
Ustekinumab is approved for PsA and is a good option for those who are not candidates for TNF-α and IL-17 inhibitors. Ustekinumab also is approved for CD. The dosing interval of 12 weeks makes ustekinumab convenient for patients. Two dosages exist based on the patient’s weight, offering an advantage to obese patients.
IL-17/IL-17R Inhibitors
Activated TH17 cells produce the IL-17 cytokine family, which stimulates keratinocyte proliferation and dermal inflammation. Secukinumab is a fully human monoclonal antibody, and ixekizumab is a humanized monoclonal antibody; both target IL-17A. Brodalumab targets the IL-17A receptor.
Efficacy and Safety
IL-17 inhibitors showed impressive and rapid responses in trials.21-23 The subsets of patients who responded well and continued treatment in extension trials demonstrated that these treatments maintain efficacy over time.24-26
In addition to tuberculosis reactivation, there is a small increased risk for cutaneous candidiasis with IL-17 inhibitors, which can be managed without stopping treatment. Laboratory abnormalities were limited to mild neutropenia, which was not associated with increased risk for infection.21-23 With ixekizumab, neutropenia was seen more commonly in the first 12 weeks.22
IL-17 is highly expressed in the gut mucosa, and its inhibition is thought to weaken the barrier function of the gut mucosa, promoting inflammation. As a consequence, this class is contraindicated in patients with IBD due to exacerbations of existing IBD and cases of new-onset IBD.21-23 Symptoms of diarrhea, abdominal pain, blood in stool, or nighttime stooling on review of gastrointestinal tract symptoms should prompt further evaluation.
Brodalumab has a unique warning for risk for suicidal ideation and behavior.23 Depression is more common in the psoriasis population in general; therefore, physicians should be aware of this potential comorbidity regardless of the treatment plan. Because the response rates are so impressive with brodalumab, the Risk Evaluation and Mitigation Strategy (REMS) program was established to ensure understanding of this risk so that patients can be appropriately counseled and managed.
Patient Selection
The improvement in psoriasis is rapid and may occur as early as week 2 to 3 of treatment after initiation of IL-17 inhibitors. Ixekizumab and secukinumab also are approved for PsA. Although improvement in joint disease is not as fast as with the anti-TNF inhibitors, notable improvement occurs by week 20 to 24.27
IL-23 Inhibitors
Guselkumab and tildrakizumab are the newest biologics for psoriasis, approved in 2017 and 2018, respectively. Both are monoclonal antibodies against the p19 subunit of IL-23, which blocks activation of TH17 cells.
Efficacy and Safety
Guselkumab and tildrakizumab demonstrated efficacy with minimal AEs or precautions noted thus far.28,29 Infections are again a risk, making tuberculosis testing the only recommended monitoring.
Patient Selection
Both medications offer another effective and safe option for patients with psoriasis. Similar to ustekinumab, the dosing interval of 12 weeks for tildrakizumab is ideal for patients who have needle phobia or are unable to administer their own injections.