General Information

Tremfya (guselkumab) is an interleukin-23 blocker. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of pro-inflammatory cytokines and chemokines.

Tremfya is specifically indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Tremfya is specifically indicated for adult patients with active psoriatic arthritis.

Tremfya is supplied as an injection for subcutaneous administration. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.

Clinical Results

Moderate-to-severe plaque psoriasis: The FDA approval of Tremfya was based on results from a clinical development program that included more than 2,000 patients in the Phase III VOYAGE 1, VOYAGE 2 and NAVIGATE studies.

In the VOYAGE 1 and VOYAGE 2 studies, 1,443 subjects were randomized to either Tremfya (100 mg at Weeks 0 and 4 and every 8 weeks thereafter), placebo or adalimumab (80 mg at Week 0 and 40 mg at Week 1, followed by 40 mg every other week thereafter). Both trials assessed the responses at Week 16 compared to placebo for the two co-primary endpoints: the proportion of subjects who achieved an IGA score of 0 (“cleared”) or 1 (“minimal”) and the proportion of subjects who achieved at least a 90% reduction from baseline in the PASI composite score (PASI 90). VOYAGE 1: IGA score 85% vs. 7% and PASI 90 73% vs. 3% for Tremfya vs. placebo, respectively. VOYAGE 2: IGA score 84% vs. 8% and PASI 90 70% vs. 2% for Tremfya vs. placebo, respectively.

NAVIGATE evaluated the efficacy of 24 weeks of treatment with Tremfya in subjects (N=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with ustekinumab (dosed 45 mg or 90 mg according to the subject’s baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with ustekinumab treatment every 12 weeks or switch to Tremfya 100 mg at Weeks 16, 20, and every 8 weeks thereafter. In subjects with an inadequate response (IGA ≥2 at Week 16 to ustekinumab), greater proportions of subjects on Tremfya compared to ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement at Week 28 (31% vs 14%, respectively; 12 weeks after randomization).

Active Psoriatic Arthritis: The FDA approval of Tremfya was based on results from two pivotal Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which evaluated the efficacy and safety of Tremfya administered by subcutaneous injection in adults with active PsA compared to placebo. The results showed that a significant percentage of patients treated with Tremfya reached the studies' primary endpoint of ACR20 at 24 weeks, with 52 and 64 percent of patients achieving an ACR20 response compared to 22 and 33 percent in patients treated with placebo in DISCOVER-1 and DISCOVER-2, respectively. In addition, treatment with Tremfya improved patients' symptoms, which included skin manifestations of psoriasis, physical functioning as measured by the HAQ-DI (Health Assessment Questionnaire Disease Index) and SF-36 Physical Component Summary score, and soft tissue (enthesitis and dactylitis). Tremfya also resulted in improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F).

Side Effects

Adverse effects associated with the use of Tremfya may include, but are not limited to, the following:

upper respiratory infections

headache

injection site reactions

arthralgia

diarrhea

gastroenteritis

tinea infections

herpes simplex infections

Tremfya may increase the risk of infection. Evaluate patient for tuberculosis prior to initiating treatment with Tremfya.

Mechanism of Action

Tremfya is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of pro-inflammatory cytokines and chemokines.