Guselkumab

Guselkumab is an approved, monoclonal, humanized HuCAL antibody directed against interleukin-23. The IL-23 antibody is able to reduce the number of pathological Th17 cells. Guselkumab is injected subcutaneously and has been available as a first-line therapy for adult patients with moderate to severe plaque psoriasis since November 2017.

Data from the VOYAGE 1 study showed significant improvements in patients treated with the drug compared to placebo: defined as at least 90 percent improvement in Psoriasis Area Severity Index (PASI 90, near complete skin clearance) and Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin at week 16 of treatment - co-primary endpoint of the study.

Patients treated with the drug demonstrated significantly greater improvements in enthesitis and dactylitis as well as health-related quality of life (measured by SF36-SF36 scores and SF36-MCS scores) at week 24 compared to placebo.

Comparison with Humira: The VOYAGE-1 study also included a comparator arm that evaluated the drug against Humira (adalimumab). This demonstrated superiority of guselkumab in key endpoints of the study and over 48 weeks of treatment. At week 24, the proportion of guselkumab patients achieving a PASI 90 response was 80.2 percent compared to 53.0 percent in the adalimumab group.

The VOYAGE-2 study (n=496 patients), a randomized, double-blind Phase III study, was conducted at 115 study sites worldwide. In this study, the IL-23 antibody also proved to be superior to adalimumab. Patients who did not respond to adalimumab were treated with guselkumab. In this group, 66.1% achieved a PASI 90 at week 48 with guselkumab.

Moderate to severe psoriasis. Several studies are available - also in comparison with already established preparations - that demonstrate excellent efficacy in psoriasis.

Since November 2020, guselkumab has been approved as a first-line biologic in monotherapy or combination therapy with methotrexate for the treatment of active psoriatic arthritis in adults who have had an inadequate response to or are intolerant of disease-modifying anti-rheumatic drugs ( DMARDs).

Guselkumab is administered as a subcutaneous injection in a dosage of 100 mg. The first two injections are given four weeks apart. In the maintenance phase, patients receive the injections every 8 weeks.

• nasopharyngitis in 10.3% of (494) participants.
• Headache in 5.9% of the participants.
• Upper respiratory tract infections in 5.1% of the participants.

Tremfya®

The drug Stelara, which blocks IL-23 as well as IL-12, also pursues an analogous approach.

1. Gordon KB et al.(2015) A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015 Jul 9;373(2):136-44.
2. Girolomoni G et al (2017) The role of IL-23 and the IL-23/TH 17 immune axis in the pathogenesis andtreatment of
   psoriasis.J Eur Acad Dermatol Venereol 31:1616-1626.
3. Reich K et al (2017) Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol 76:418-431.
4. Current Tremfya® SmPC
5. Schmidt B (2021) Approval expansion as a firt-line biologic for active psoriatic arthritis. Compendium Dermatology 2021: 13