The Medical Letter on Drugs and Therapeutics
Guselkumab (Tremfya) for Psoriasis
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The FDA has approved the interleukin (IL)-23 blocker guselkumab (Tremfya – Janssen) for treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Guselkumab is the first selective IL-23 blocker to become available in the US.

MECHANISM OF ACTION — IL-23 is a cytokine involved in normal inflammatory and immune responses. Guselkumab is a fully human monoclonal IgG1 antibody that selectively binds to the p19 subunit of IL-23, inhibiting it from binding to the IL-23 receptor and preventing downstream release of pro-inflammatory cytokines (such as IL-17A) and chemokines.

STANDARD TREATMENT — Plaque psoriasis is a chronic, inflammatory, immune-mediated disorder. Mild to moderate psoriasis is generally treated with topical corticosteroids. Topical vitamin D analogs and the retinoid tazarotene (Tazorac, and others) are alternatives that can be used alone or in combination with topical corticosteroids. For patients with moderate to severe disease, systemic options include the phosphodiesterase type-4 inhibitor apremilast (Otezla), the tumor necrosis factor (TNF) inhibitors etanercept (Enbrel) and adalimumab (Humira), the IL-12 and IL-23 antagonist ustekinumab (Stelara), and the IL-17A antagonists secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). Other options for severe disease include methotrexate, cyclosporine, the oral retinoid acitretin (Soriatane, and generics), and the TNF inhibitor infliximab (Remicade, and biosimilars). UVB phototherapy or UVA photochemotherapy can be used for treatment of widespread or unresponsive disease.1

CLINICAL STUDIES — Approval of guselkumab for treatment of plaque psoriasis was based on the results of three trials in patients with moderate to severe disease. In one trial (NAVIGATE), 871 patients received open-label treatment with the IL-12/23 antagonist ustekinumab at weeks 0 and 4. After 16 weeks, 268 patients whose psoriasis had not adequately responded to ustekinumab were randomized (double-blind) to receive guselkumab or continue ustekinumab for another 24 weeks. Patients who switched to guselkumab had clear or almost clear skin at significantly more visits between weeks 28 and 40, the primary endpoint, than those who continued receiving ustekinumab. They also achieved a ≥90% reduction in the Psoriasis Area and Severity Index score (PASI 90) at week 52 significantly more often than those who continued receiving ustekinumab (51.1% vs 24.1%).2

In a double-blind trial (VOYAGE 1), 837 patients were randomized to treatment with guselkumab, the TNF inhibitor adalimumab, or placebo. At week 16, significantly more patients had achieved a PASI 90 response with guselkumab (73.3%) than with adalimumab (49.7%) or placebo (2.9%). Patients receiving guselkumab were also significantly more likely to have clear or almost clear skin at week 16 (85.1%) than those receiving adalimumab (65.9%) or placebo (6.9%).3

In an open-label extension trial (VOYAGE 2), 112 patients enrolled in VOYAGE 1 whose psoriasis had not responded to adalimumab by week 28 were switched to guselkumab; 20 weeks later, 66.1% of these patients had achieved a PASI 90 response.4

ADVERSE EFFECTS — In clinical trials, tinea infections and hepatic enzyme elevations were reported more frequently with guselkumab (1.1% and 2.6%) than with placebo (0% and 1.9%). Serious infections, including fungal infections and reactivation of tuberculosis, have occurred in patients treated with the drug. Antibody formation has been reported with use of guselkumab; whether it reduces the effectiveness of the drug is not known.

PREGNANCY AND LACTATION — No data are available on the use of guselkumab in pregnant women. Whether guselkumab is present in human breast milk is not known, but human IgG antibodies cross the placenta and can be found in breast milk.

DRUG INTERACTIONS — No clinically significant drug interactions have been reported with use of guselkumab, but blocking IL-23 could affect formation of CYP isozymes and metabolism of CYP substrates. Patients being treated with guselkumab should not receive live vaccines.

CONCLUSION — The IL-23 blocker guselkumab (Tremfya) appears to be effective and generally safe for treatment of moderate to severe plaque psoriasis. In one clinical trial, it was more effective than the TNF inhibitor adalimumab (Humira). In another trial in patients whose disease had not responded to ustekinumab (Stelara), guselkumab was more effective than continuing ustekinumab. How guselkumab compares to other drugs for this indication remains to be determined.

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