What is the efficacy of Tremfya (guselkumab) for moderate to severe plaque psoriasis?

Efficacy of Tremfya (Guselkumab) for Psoriasis

Tremfya (guselkumab) is highly effective for moderate-to-severe plaque psoriasis, with 70-73% of patients achieving PASI 90 at week 16, superior efficacy compared to adalimumab, and sustained long-term responses maintained for up to 5 years. 1

Strength of Recommendation

The American Academy of Dermatology and National Psoriasis Foundation provide a Grade A recommendation for guselkumab as monotherapy for moderate-to-severe plaque psoriasis in adults. 1

Efficacy Data from Pivotal Trials

Short-Term Efficacy (Week 16)

• PASI 90 achievement: 70.0-73.3% of patients in the VOYAGE 1 and VOYAGE 2 trials achieved at least 90% improvement in psoriasis severity 1, 2
• Superior to adalimumab: 70.0% with guselkumab vs 46.8% with adalimumab vs 2.4% with placebo achieved PASI 90 at week 16 1
• IGA 0/1 (clear/minimal skin): Significantly higher proportion achieved this endpoint compared to adalimumab at week 16 3

Long-Term Efficacy (Up to 5 Years)

• Sustained response through 2 years: Benefits maintained for up to 2 years in VOYAGE trials 3
• Real-world data through 148 weeks: 97.6% achieved PASI 75,82.9% achieved PASI 90, and 63.4% achieved PASI 100 after 148 weeks of treatment 4
• Drug survival: 96% of patients remained on treatment after 2 years in real-world settings 4

Comparative Efficacy Against Other Biologics

• Superior to secukinumab at week 48: 84% with guselkumab vs 70% with secukinumab achieved PASI 90 (p<0.0001) in the ECLIPSE trial 5
• Effective in biologic failures: Among adalimumab non-responders who switched to guselkumab, 66.1% achieved PASI 90 at week 48 1
• Improved responses in ustekinumab inadequate responders: NAVIGATE trial showed better responses with guselkumab compared to continuing ustekinumab between weeks 28-40 1

Dosing Regimen

The FDA-approved and guideline-recommended dose is 100 mg by subcutaneous injection at week 0, week 4, and every 8 weeks thereafter. 1

• Self-administered subcutaneous injection 1
• Less frequent dosing (every 8 weeks) may be preferred by patients compared to biologics requiring more frequent administration 1

Special Populations and Psoriasis Subtypes

Guselkumab receives Grade A recommendation for scalp, nail, and plaque-type palmoplantar psoriasis. 1

Factors Affecting Response

• Obesity: Non-obese patients achieved higher PASI 100 rates (86.4%) compared to obese patients (38.9%) at week 148 4
• Prior biologic exposure: Bio-naïve patients achieved better outcomes (86.7% PASI 100) vs bio-experienced patients (50.0%) at week 148; previous biologic therapy was a negative prognostic factor (p=0.005) 4

Time to Response Assessment

Definitive response to guselkumab should be assessed after 12 weeks of continuous therapy. 1

• Rapid initial response: PASI decreased from 16.2 to 3.2 at week 12 in real-world data 4
• For partial responders, consider adding topical corticosteroids, vitamin D analogues, methotrexate, or ultraviolet B light 1

Safety Profile

Guselkumab demonstrates favorable long-term safety through 5 years of treatment with 8662 patient-years of exposure. 6

Key Safety Findings

• Adverse event rates comparable to placebo: 346/100 patient-years with guselkumab vs 341/100 patient-years with placebo during controlled period 6
• Infection rates: 95.9/100 patient-years with guselkumab vs 83.6/100 patient-years with placebo; most commonly nasopharyngitis, headache, and upper respiratory tract infection 6, 2
• Serious adverse events: Low rate of 5.3/100 patient-years through long-term follow-up 6
• No inflammatory bowel disease cases: Zero cases of Crohn disease or ulcerative colitis related to guselkumab 6
• Malignancy risk: Low rate of 0.7/100 patient-years, though long-term studies are needed to fully define cancer risk 1, 6
• MACE (major adverse cardiovascular events): Low rate of 0.3/100 patient-years 6

Quality of Life Improvements

Treatment with guselkumab significantly improved health-related quality of life and patient-reported outcomes across all trials. 3

Clinical Positioning

For patients with both psoriatic arthritis and significant skin involvement, IL-23 inhibitors like guselkumab are recommended over TNF inhibitors according to EULAR guidelines. 7