Tremfya (Guselkumab): An IL-23 Inhibitor for Psoriasis Treatment
Tremfya (guselkumab) is a human monoclonal antibody that selectively blocks interleukin-23 (IL-23) by binding to its p19 subunit, FDA-approved as a highly effective biologic therapy for moderate-to-severe plaque psoriasis in adults. 1, 2
Mechanism of Action and Classification
Tremfya belongs to the IL-23 inhibitor class of biologics. It works by:
- Selectively targeting the p19 subunit of IL-23
- Blocking IL-23-mediated signaling pathways
- Disrupting the inflammatory cascade involved in psoriasis pathogenesis
- Acting as a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody with an approximate molecular weight of 147 kDa 2, 3
FDA-Approved Indications
Tremfya is approved for:
- Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy 1, 2
- Active psoriatic arthritis in adults 2
- Moderately to severely active Crohn's disease 2
- Moderately to severely active ulcerative colitis 2
Dosing and Administration
For plaque psoriasis and psoriatic arthritis:
- 100 mg administered by subcutaneous injection at weeks 0 and 4, then every 8 weeks thereafter 1, 2
- Available as prefilled syringes, prefilled pens (TREMFYA PEN), or One-Press patient-controlled injectors 2
For inflammatory bowel disease (Crohn's disease and ulcerative colitis):
- Initial induction doses administered intravenously in a healthcare facility
- Maintenance doses administered subcutaneously 2
Clinical Efficacy
Tremfya demonstrates superior efficacy compared to other biologics:
- In VOYAGE trials, guselkumab showed significantly higher PASI 90 response rates (70.0%) compared to adalimumab (46.8%) at week 16 1, 4, 5
- Maintains efficacy for up to 2 years in clinical trials 3
- Effective for patients who failed other biologics, including TNF inhibitors and ustekinumab 4, 3
- Particularly effective for difficult-to-treat areas including scalp, nail, and palmoplantar psoriasis 1
Safety Profile
Common side effects include:
- Respiratory tract infections
- Headache
- Injection site reactions
- Joint pain (arthralgia)
- Diarrhea
- Gastroenteritis
- Fungal skin infections 2
Serious potential adverse events:
- Serious allergic reactions
- Infections (including tuberculosis)
- Liver problems (particularly in IBD patients) 2
Monitoring Requirements
- Tuberculosis screening prior to initiation
- Assessment of response after 12 weeks of continuous therapy
- Monitoring for signs of infection or allergic reactions
- Liver function tests for patients with IBD 1, 2
Special Considerations
- Pregnancy: Limited human data; pregnancy registry available for monitoring outcomes
- Breastfeeding: Unknown if guselkumab passes into breast milk
- Immunizations: Live vaccines should be avoided during treatment
- Infections: Use caution in patients with chronic infections or history of recurrent infections 2
Advantages Over Other Biologics
- Higher efficacy rates compared to TNF inhibitors like adalimumab
- Convenient dosing schedule (every 8 weeks after induction)
- Effective for patients who have failed other biologic therapies
- Targets a different inflammatory pathway than TNF inhibitors, offering an alternative mechanism of action 1, 4, 3
Tremfya represents an important addition to the psoriasis treatment armamentarium, particularly for patients with moderate-to-severe disease who have failed or are unsuitable for other systemic therapies.