Clinical Pharmcology Update: Tremfya

The FDA has approved Tremfya (guselkumab, Janssen Biotech, Inc) for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Tremfya is administered by subcutaneous injection.¹ It is the only biologic therapy approved that selectively blocks only interleukin-23 (IL-23), a key cytokine in plaque psoriasis. Psoriasis is characterized by raised, inflamed red plaques on the skin that are caused by overproduction of skin cells. It is a chronic autoimmune inflammatory disorder that affects more than 7.5 million Americans.²

Pharmacology and Pharmacokinetics

Tremfya is a human monoclonal IgG1λ antibody. It inhibits the release of pro-inflammatory cytokines and chemokines by selectively binding to the p19 subunit of IL-23. Tremfya exhibited linear pharmacokinetics after subcutaneous administration in healthy patients and patients with psoriasis. The mean half-life was about 15 to 18 days in patients with psoriasis.¹

Dosage and Administration

Tremfya should be given as a 100-mg subcutaneous injection at weeks 0 and 4 and every 8 weeks thereafter.¹

Clinical Trials

Three multicenter, randomized, double-blind trials (VOYAGE 1, VOYAGE 2, and NAVIGATE) evaluated the role of Tremfya in patients aged 18 years and older with moderate to severe plaque psoriasis who were eligible for systemic therapy or phototherapy.

In VOYAGE 1 and VOYAGE 2, 1443 patients were randomized to receive Tremfya, placebo, or adalimumab. Both trials had 2 coprimary endpoints assessed at week 16, compared with placebo: the proportion of patients to achieve an Investigator’s Global Assessment (IGA) score of 0 (cleared) or 1 (minimal) and the proportion of patients to achieve at least a 90% reduction from baseline in the Psoriasis Area and Severity Index composite score (PASI 90). The study results showed that more than 80% of patients using Tremfya achieved the IGA score, and at least 70% of the Tremfya group achieved the PASI 90. Of the Tremfya patients achieving the PASI 90 at week 28, 89% of those who continued treatment with the medication maintained their response at week 48. In addition, the Tremfya group demonstrated an improvement in scalp symptoms compared with placebo at week 16, as well as greater psoriasis symptom relief compared with adalimumab at week 24.

In NAVIGATE, the efficacy of 24 weeks of treatment with Tremfya was evaluated in 268 patients who had not achieved an adequate response after 16 weeks of initial treatment with ustekinumab. Study participants were randomized to either continue with ustekinumab treatment every 12 weeks or switch to Tremfya 100 mg at weeks 16 and 20 and every 8 weeks thereafter. At week 28, 31% of patients using Tremfya achieved an IGA score of 0 or 1 compared with 14% of those using ustekinumab.^1,2

Contraindications, Warnings and Precautions

There are no contraindications to treatment with Tremfya. Treatment with Tremfya may increase the risk of infection. In clinical trials, upper respiratory tract infections (URTIs), gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the Tremfya group than in the placebo group. Patients with any clinically important active infection should not begin treatment with Tremfya until the infection resolves or is adequately treated. Patients should be counseled to seek immediate medical attention if signs or symptoms of a clinically important chronic infection or acute infection occur. If a serious infection occurs, treatment with Tremfya should be discontinued until the infection has resolved.

Patients should be evaluated for tuberculosis infection prior to initiating treatment with Tremfya. Tremfya should not be given to patients with active tuberculosis.

The use of live vaccine in patients receiving Tremfya should be avoided.

The most common (≥1% incidence) adverse reactions associated with Tremfya include URTIs, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.¹

Monica Holmberg, PharmD, BCPS, earned her PharmD from the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Healthcare System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.

References

• Tremfya [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2017. janssenlabels.com/package-insert/product- monograph/prescribing-information/TREMFYA- pi.pdf. Accessed November 27, 2017.
• Janssen announces U.S. FDA approval of Tremfya (guselkumab) for the treatment of moderate to severe plaque psoriasis [news release]. Horsham, PA: Janssen Biotech Inc; July 13, 2017. jnj.com/media-center/press- releases/janssen-announces- us-fda- approval-of- tremfya- guselkumab-for- the-treatment- of-moderate- to-severe- plaque-psoriasis. Accessed November 27, 2017.