Tremfya for Plaque Psoriasis: What Pharmacists Should Know

Psoriasis is a common skin condition characterized by red, itchy, and scaly skin patches or joint pain. According to the American Academy of Dermatology approximately 7.5 million people in the United States have psoriasis which can result in troubling symptoms, diminished quality of life, and increased healthcare costs.¹ Plaque psoriasis is the most common type of psoriasis making up approximately 80% of all cases.

In July 2017, the FDA approved Janssen’s Tremfya (guselkumab), an interleukin (IL)-23 blocker, for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. With its approval, Tremfya became the first and only approved biologic therapy that selectively blocks IL-23, a cytokine that plays an important role in plaque psoriasis.

This article highlights several key therapeutics areas with Tremfya that every pharmacist should know.

Indication²

Tremfya is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The safety and efficacy of Tremfya in pediatric patients (less than 18 years of age) have not been established.

Mechanism of Action

Tremfya is a human monoclonal antibody that selectively binds to the p19 subunit of IL-23 ,thereby inhibiting its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Through its interaction with IL-23, Tremfya effectively inhibits the release of pro-inflammatory cytokines and chemokines.

Formulation and Storage

Tremfya is available as a clear and colorless to light yellow solution in a single-dose 100 mg/mL prefilled syringe. Each syringe contains 1 mL of medication. It should be stored in refrigeration at 2°C (35.6°F) and protected from light in the original carton until time of use. Do not freeze or shake Tremfya.

Dosing

The recommended dose of Tremfya is 100 mg administered subcutaneously at week 0, week 4, and every 8 weeks thereafter. The medication may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment with Tremfya.

Efficacy^2,3

The efficacy of Tremfya for the treatment of plaque psoriasis was established in three multicenter, randomized, double-blind trials (VOYAGE 1, VOYAGE 2, and NAVIGATE). The studies enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had an Investigator’s Global Assessment (IGA) score of ≥3 (“moderate”) on a 5-point scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum affected body surface area (BSA) of 10%.

In VOYAGE 1 and VOYAGE 2, 1443 subjects were randomized to receive Tremfya, placebo or Humira. Both trials assessed the responses at week 16 compared to placebo for the two co-primary endpoints: (1) the proportion of subjects who achieved an IGA score of 0 (“cleared”) or 1 (“minimal”) and (2) the proportion of subjects who achieved at least a 90% reduction from baseline in the PASI composite score (PASI 90). At baseline, subjects had a median affected BSA of approximately 21%, median PASI score of 19, and 18% had a history of psoriatic arthritis. In both trials, 23% had received prior biologic systemic therapy.

As compared to placebo, Tremfya demonstrated a significantly higher IGA response of 0/1 (84-85% Tremfya vs 7-8% placebo) and PASI 90 (70-73% Tremfya vs 2-3% placebo). Additionally, Tremfya demonstrated superiority to Humira for up to 48 weeks of study duration as seen below.

VOYAGE 1

VOYAGE 2

Endpoint

Tremfya (N=115)

n (%)

Humira (N=115)

n (%)

Tremfya (N=160)

n (%)

Humira (N=81)

n (%)

IGA response of 0/1 (cleared or minimal)

Week 16

97 (84)

70 (61)

119 (74)

50 (62)

Week 24

97 (84)

62 (54)

119 (74)

46 (57)

Week 48

91 (79)

62 (54)

N/A

N/A

PASI 90 response

Week 16

84 (73)

47 (41)

102 (64)

34 (42)

Week 24

92 (80)

51 (44)

113 (71)

41 (51)

Results from an open-label extension of VOYAGE 1 found continued benefit of Tremfya for up to 2 years. At week 100, among patients initially randomized to Tremfya, 82% achieved an IGA score of 0/1 and 82% achieved a PASI 90 score.

NAVIGATE evaluated the efficacy of 24 weeks of treatment with Tremfya in 268 subjects who had not achieved an adequate response, defined as IGA ≥2 at week 16 after initial treatment Stelara. These subjects were randomized to either continue with Stelara or switch to Tremfya. In subjects with an inadequate response, greater proportions of subjects on Tremfya compared to Stelara achieved an IGA score of 0 or 1 with a ≥2 grade improvement at week 28 (31% vs 14%). They also achieved a PASI 90 at week 52 significantly more often than those who continued receiving Stelara (51.1% vs 24.1%).

Safety²

The most common adverse reactions of Tremfya reported in clinical trials include upper respiratory infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.

There is also a warning in its labeling for increased risk of infection. If a serious infection occurs, Tremfya should be discontinued until the infection resolves.

Drug Interactions

No clinically significant drug interactions have been reported with use of Tremfya; however, blocking IL-23 could affect formation of CYP450 enzymes and metabolism of CYP substrates.

Patient Counseling

Patients should be instructed to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection. Before administering Tremfya, patients should remove the prefilled syringe from the refrigerator and allow it to reach room temperature for about 30 minutes without removing the needle cap. Then visually inspect Tremfya for particulate matter and discoloration. It should not be used if the liquid contains large particles, is discolored or cloudy.

Do not inject Tremfya into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis. The recommended injection site is the front of the thighs although the lower stomach area and back of upper arms can also be used.

Remind patients if they forget to take their dose of Tremfya to inject their dose as soon as they remember. They should then take their next dose at the appropriate scheduled time.

Patients should avoid use of live vaccines while on therapy and be encouraged to communicate any history of infections to their healthcare provider. A patient should also contact their healthcare provider if they develop any symptoms of an infection while on therapy.

Product Comparison⁴

Mechanism

Administration

Doses Year 1*

Doses Year 2*

Tremfya (guselkumab)

IL-23 blocker

SQ

8

6

Stelara (ustekinumab)

IL-12 and 23 antagonist

SQ

6

4

Enbrel (etanercept)

TNF blocker

SQ

66

52

Humira (adalimumab)

TNF blocker

SQ

28

26

Remicade (infliximab)

TNF blocker

IV

8

6

Siliq (brodalumab)

IL-17A receptor antagonist

SQ

28

26

Taltz (ixekizumab)

IL-17A antagonist

SQ

18

13

Cosentyx (secukinumab)

IL-17A antagonist

SQ

17

13

Otezla (apremilast)

PDE-4 inhibitor

Oral

729

730

* Number of doses is an approximate calculation based on product labeling. Actual number of doses may vary based on age, body weight, start date, and gaps between medication administrations.

Conclusion²

In clinical studies, Tremfya was shown to be effective in reducing symptoms of plaque psoriasis as compared to placebo and Humira. It also demonstrated benefit in patients who had not responded to Stelara. The safety profile was similar to other autoimmune biologics. Tremfya may be advantageous to other biological for plaque psoriasis due to its relatively low number of injections which may improve adherence. Head to head studies would be beneficial to compare the efficacy of Tremfya versus other biologics for plaque psoriasis.

References

• Psoriasis. American Academy of Dermatology Association. www.aad.org/media/stats/conditions/psoriasis. Accessed January 19, 2017
• Tremfya [Prescribing Information]. Janssen Biotech Inc. Horsham, PA. July 2017.
• New Two-Year Tremfya (guselkumab) data shows patients with moderate to severe plaque psoriasis achieved consistent rates of skin clearance. Janssen. Sept 18, 2017. www.janssen.com/new-two-year-tremfyatm-guselkumab-data-show-patients-moderate-severe-plaque-psoriasis-achieved
• Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc.; January 19, 2017.