Introduction
Tremfya (guselkumab) is a human monoclonal antibody biologic medication developed by Janssen Pharmaceuticals. It represents a targeted therapeutic approach for immune-mediated inflammatory conditions, specifically designed to selectively inhibit interleukin-23 (IL-23), a key cytokine involved in inflammatory pathways. Approved by the FDA in 2017, Tremfya offers a novel mechanism for treating moderate-to-severe plaque psoriasis and psoriatic arthritis.
Mechanism of Action
Tremfya exerts its therapeutic effects through highly selective inhibition of interleukin-23 (IL-23). The drug binds specifically to the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor complex on cell surfaces. This targeted inhibition blocks IL-23-mediated intracellular signaling, including the JAK-STAT pathway, which subsequently reduces the production and release of pro-inflammatory cytokines (including IL-17, IL-22, and TNF-α). By interrupting this specific inflammatory cascade, Tremfya modulates the abnormal immune response characteristic of psoriatic diseases without broadly suppressing the entire immune system.
Indications
- Plaque Psoriasis: Treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
- Psoriatic Arthritis: Treatment of active psoriatic arthritis in adults
- Investigational Uses: Currently being studied for other IL-23-mediated conditions including Crohn's disease, ulcerative colitis, and hidradenitis suppurativa
Dosage and Administration
Standard Dosing:- Initial dose: 100 mg subcutaneous injection at weeks 0 and 4
- Maintenance dosing: 100 mg every 8 weeks thereafter
- For subcutaneous injection only
- Prefilled syringe or autoinjector formats available
- May be administered by healthcare professional or self-administered after proper training
- Rotate injection sites (thighs, abdomen, upper arms)
- Allow medication to reach room temperature (30 minutes) before injection
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment necessary
- Pediatric: Safety and effectiveness not established
- Pregnancy: Category B - use only if clearly needed
- Lactation: Consider benefits versus potential risks
Pharmacokinetics
Absorption: Bioavailability approximately 51% following subcutaneous administration; peak serum concentrations reached in approximately 5.5 days Distribution: Steady-state volume of distribution approximately 13.5 L; minimal tissue distribution beyond vascular space Metabolism: Degraded via proteolytic enzymes into small peptides and amino acids; no hepatic cytochrome P450 metabolism Elimination: Terminal half-life approximately 15-18 days; linear pharmacokinetics; clearance approximately 0.516 L/day Special Considerations: No meaningful differences observed based on age, gender, race, or body weight; anti-drug antibodies may develop in approximately 6% of patients, though this rarely affects pharmacokinetics or efficacyContraindications
- History of serious hypersensitivity reaction to guselkumab or any component of the formulation
- Patients with active tuberculosis or other serious infections
- Patients with history of severe allergic reactions to monoclonal antibodies
Warnings and Precautions
Infections: Tremfya may increase risk of infections. Serious bacterial, fungal, and viral infections have been reported. Evaluate patients for tuberculosis infection before initiating treatment. Hypersensitivity Reactions: Anaphylaxis and other hypersensitivity reactions may occur. Discontinue Tremfya if serious reaction occurs. Immunizations: Avoid live vaccines during treatment. Ensure patients are up-to-date with all immunizations before initiation. Theoretical Risk of Malignancy: IL-23 inhibition may affect immune surveillance against malignancies. Monitor patients for signs of malignancy. Inflammatory Bowel Disease: Exacerbation of Crohn's disease and ulcerative colitis has been observed. Use with caution in patients with history of IBD. Laboratory Monitoring: No specific laboratory monitoring required, but baseline assessment of infection status recommended.Drug Interactions
Live Vaccines: Concurrent administration not recommended CYP450 Substrates: IL-23 inhibition may affect formation of CYP450 enzymes; monitor drugs with narrow therapeutic indices Other Biologics: Increased risk of immunosuppression with concomitant use; generally not recommended TNF Inhibitors: Limited data on combination therapy; increased infection risk possibleAdverse Effects
Most Common (≥1%):- Upper respiratory infections (14%)
- Headache (4%)
- Injection site reactions (3%)
- Arthralgia (3%)
- Diarrhea (2%)
- Gastroenteritis (2%)
- Tinea infections (2%)
- Herpes simplex infections (1%)
- Serious infections (1%)
- Hypersensitivity reactions
- Hepatic enzyme elevations
- Inflammatory bowel disease exacerbation
- Anaphylaxis
- Urticaria
- Rash
Monitoring Parameters
Baseline Assessment:- Tuberculosis screening (PPD or interferon-gamma release assay)
- Hepatitis B and C screening
- Complete blood count
- Liver function tests
- Pregnancy test if applicable
- Vaccination status review
- Signs and symptoms of infection at each visit
- Injection site reactions
- New or worsening psoriasis symptoms
- Joint symptoms in psoriatic arthritis patients
- Signs of inflammatory bowel disease
- Response to therapy (PASI scores, joint assessment)
- Patient adherence to dosing schedule
- Monitor for signs of tuberculosis during and after treatment
- Annual skin examination for patients at high risk for skin cancer
- Monitor for neurologic symptoms (rare cases of reversible posterior leukoencephalopathy syndrome reported)
Patient Education
Administration:- Proper injection technique training provided by healthcare provider
- Storage requirements: refrigerate at 2°C to 8°C; do not freeze
- Allow medication to reach room temperature before injection
- Dispose of needles and syringes in approved sharps container
- Report any signs of infection (fever, cough, flu-like symptoms)
- Seek immediate medical attention for serious infections
- Inform all healthcare providers about Tremfya treatment
- Avoid live vaccines during treatment
- Discuss travel plans that may increase infection risk
- Report new or worsening medical conditions
- Inform dentist about medication before procedures
- Maintain regular appointment schedule
- Report any injection site reactions
- Discuss pregnancy plans with healthcare provider
- Do not discontinue medication without medical guidance
- Continue other prescribed psoriasis treatments as directed
- Maintain good skin care practices
- Sun protection recommended
- Healthy lifestyle choices to support overall immune function
References
1. Reich K, Armstrong AW, Langley RG, et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet. 2019;394(10201):831-839.
2. Deodhar A, Helliwell PS, Boehncke WH, et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10230):1115-1125.
3. Tremfya [package insert]. Titusville, NJ: Janssen Biotech, Inc.; 2023.
4. Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405-417.
5. McInnes IB, Behrens F, Mease PJ, et al. Secukinumab versus adalimumab for treatment of active psoriatic arthritis (EXCEED): a double-blind, parallel-group, randomised, active-controlled phase 3b trial. Lancet. 2020;395(10235):1496-1505.
6. FDA-approved labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761061s017lbl.pdf
7. European Medicines Agency Assessment Report: https://www.ema.europa.eu/en/documents/assessment-report/tremfya-epar-public-assessment-report_en.pdf
Note: This monograph provides general information and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.