Cosentyx (Secukinumab): First IL-17A Antagonist Receives FDA Approval for Moderate-to-Severe Plaque Psoriasis

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Loretta Fala
Medical Writer

Psoriasis, the most prevalent autoimmune disease in the United States, affects approximately 7.5 million people.1 A chronic, relapsing disease, psoriasis is characterized by thick patches of inflamed scaly skin resulting from excessive proliferation of skin cells.1,2 Psoriasis is designated as “moderate” if it involves 3% to 10% of the body surface and “severe” if it involves more than 10% of the body.3 An estimated 25% of psoriasis cases are moderate or severe.4

Patients with psoriasis are at an increased risk for psoriatic arthritis, heart disease, stroke, hypertension, type 2 diabetes, eye disorders, and obesity.2 Psoriatic arthritis affects up to 30% of patients with psoriasis.1 Psoriasis also increases the risk for Parkinson’s disease, kidney disease, and other autoimmune diseases.2 In some cases, psoriasis can be disfiguring and lead to disability.1

Plaque psoriasis is the most common form of psoriasis, appearing as raised, red patches covered with a silver or white scaly accumulation of dead skin cells. These patches, which appear most often on the knees, elbows, scalp, and lower back, can be itchy and painful.5

Psoriasis, often misperceived as simply a cosmetic problem, is a major health problem for nearly 60% of those affected.4 Aside from having a profound impact on patients’ quality of life and self-esteem, psoriasis can lead to depression, social isolation, and diminished work function and productivity.2

Furthermore, psoriasis is associated with considerable financial burden for patients and for the healthcare system. Results of a systematic review indicate that the total annual US costs attributed to psoriasis were $35.2 billion in 2013, reflecting $12.2 billion in incremental medical costs, $11.8 billion in diminished health-related quality of life, and $11.2 billion in lost productivity.6

Effective management of psoriasis demands ongoing monitoring and treatment. The therapeutic goals for psoriasis include slowing skin growth (to reduce inflammation and plaque formation) and smoothing the skin.2

Psoriasis treatments are used alone or in combination with other therapies.5 Topical treatments for psoriasis include topical corticosteroids, vitamin D analogs, anthralin, topical retinoids, calcineurin inhibitors, salicylic acid, and coal tar.2 Phototherapy with artificial ultraviolet A or B light is sometimes used alone or in combination with medications.

Systemic therapies (oral or injectable) also are used, including methotrexate, retinoids, cyclosporine, and the biologic immunomodulator agents, including the tumor necrosis factor-alpha inhibitors adalimumab (Humira), etanercept (Enbrel), and infliximab (Remicade), as well as the interleukin (IL)-12/23 inhibitor ustekinumab (Stelara).2

Cosentyx a New Treatment Option for Plaque Psoriasis

On January 21, 2015, secukinumab (Cosentyx; Novartis), a human IL-17A antagonist, was approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderate-to-severe plaque psoriasis.7 Secukinumab, a biologic immunomodulator drug administered by subcutaneous injection, is indicated for patients who are candidates for systemic therapy or photother­apy or a combination of both therapies.7,8 Secukin­umab is the first IL-17A to receive FDA approval for the treatment of patients with moderate-to-severe plaque psoriasis.9

As part of its approval, the FDA required the manufacturer to include a medication guide to inform patients that because secukinumab affects the immune system, it may increase the risk for infection.7

Commenting on this approval, Amy Egan, MD, MPH, the FDA’s Deputy Director of the Office of Drug Evaluation III, said, “Plaque psoriasis can cause significant skin irritation and discomfort for patients, so it is important to have a variety of treatment options available to patients.”7

Dosing and Administration

Secukinumab for injection is administered via the Sensoready pen or a prefilled syringe. The recommended dose of secu­kinumab is 300 mg by subcutaneous injection at weeks 0, 1, 2, 3, and 4, followed by 300 mg every 4 weeks. For some pa­tients, a dose of 150 mg may be acceptable.8

Directions for preparing the Sensoready pen and prefilled syringe are included in the drug’s prescribing information. The secukinumab lyophilized powder is reconstituted in a vial with sterile water for injection. Reconstitution should be performed by a healthcare provider.8

Secukinumab is available in several dosage strengths and injection forms, including 150-mg/mL solution in a single-use Sensoready pen; 150-mg/mL solution in a single-use prefilled syringe; and 150-mg lyophilized powder in a single-use vial for reconstitution for healthcare professional use only.8

Mechanism of Action

Elevated levels of IL-17A are found in psoriatic plaques. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the IL-17A cytokine and inhibits its interaction with the IL-17 receptor. Secukinumab in­hibits the release of pro­inflammatory cytokines and chemokines.8

Treatment with secukinumab may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques.8

Clinical Trials

The safety and effectiveness of secukinumab were evaluated in 4 multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trials comprising 2403 patients with plaque psoriasis who were candidates for phototherapy or systemic therapy.7,8 Enrolled patients were aged ≥18 years, had plaque psoriasis involving at least 10% of body surface area, and a Psoriasis Area and Severity Index (PASI) score ≥12.8

In the 4 trials, the end points were (1) the proportion of patients whose PASI score was reduced by at least 75% (PASI 75) from baseline to week 12 and (2) treatment success (clear or almost clear) according to the 2011 modified version of the Investigator’s Global Assessment.8

Trials 1 and 2: The ERASURE and FIXTURE Studies

The ERASURE study (Trial 1) was a 52-week, randomized, placebo-controlled trial that included 738 patients who received subcutaneous therapy at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. Patients were randomized to secukin­umab 300-mg or 150-mg doses for the first 4 weeks, followed by the same dose every 4 weeks, or to placebo.8,10

The FIXTURE study (Trial 2), also a 52-week, randomized, placebo-controlled trial, included 1306 patients; 327 patients received secukinumab 300 mg, 327 patients received secu­kinumab 150 mg, 326 patients received placebo, and 323 patients received a biologic active control (etanercept 50 mg twice weekly for 12 weeks, then once weekly).8,10 This discussion is limited to the data related to the secukinumab and the placebo groups.

The results of Trials 1 and 2 are shown in Table 1. In both studies, a greater proportion of patients who received secukinu­mab than those who received placebo or a biologic control met the PASI 75 criterion at week 12.10 At week 12 of Trial 1, a PASI 90 response was achieved in 59% of the secukinumab 300-mg group, 39% of the 150-mg group, and only 1% of the placebo group.8 At the same point in Trial 2, a PASI 90 response was achieved in 54% and 42% of the secukinumab groups versus 2% of the placebo group.8 The investigators concluded that the effectiveness of secukinumab in these trials validated IL-17A as a therapeutic target.10

Table 1

With continued treatment through 52 weeks in Trial 1, the initial PASI 75 responses were maintained in 81% of patients receiving secukinumab 300 mg and 72% of those receiving secukinumab 150 mg. In patients whose skin was clear or almost clear at week 12, responses were maintained for 74% of patients receiving secukinumab 300 mg and 59% of those receiving secukinumab 150 mg.8

At week 12 in both trials, improvements (vs placebo) in the signs and symptoms of itching, pain, and scaling were reported in the 39% of patients who participated in self-reported assessments.8

Trials 3 and 4: The FEATURE and JUNCTURE Studies

The FEATURE study (Trial 3) included 177 patients randomized in a 1:1:1 manner to secukin­umab 300 mg, secukinumab 150 mg, or to placebo. In this study, treatment was self-administered via a prefilled syringe once weekly to week 4, followed by the same dose every 4 weeks for up to 12 weeks.8,11

In the JUNCTURE study (Trial 4), 182 patients were randomized to receive secukinumab 300 mg, secukinumab 150 mg, or placebo. Treatment was self-administered via the Sensoready pen once weekly to week 4, followed by the same dose every 4 weeks for up to 12 weeks.8,12

The results of Trials 3 and 4 are shown in Table 2. In both studies, secu­kinumab 300 mg and 150 mg were superior to placebo at week 12.8,11,12 The PASI 90 responses at week 12 were similar to those in Trials 1 and 2.8 Moreover, the secukin­umab prefilled syringe (Trial 1) and Sensoready/autoinjector pen (Trial 2) were associated with high usability.11,12

Table 2

Adverse Events

The most common adverse reactions (>2%) associated with secukin­umab in clinical trials were nasopharyngitis, diarrhea, and upper respiratory tract infection. Additional adverse events reported in >1% of patients using secukinumab were rhinitis, oral herpes, pharyngitis, urticarial, and rhinorrhea.

The rates of adverse reactions reported by >1% of patients with plaque psoriasis through week 12 in the 4 primary clinical trials are shown in Table 3.8

Table 3

Contraindications

Secukinumab treatment is contraindicated in individuals who have had a serious hypersensitivity reaction to secukinumab or to any of its excipients.8

Drug Interactions

Live vaccines. Before initiating therapy with secukinumab, patients should receive all age-appropriate immunizations according to current immunization guidelines. Patients receiving secukinumab should not receive live vaccines.8

Nonlive vaccines. Patients using secukinumab may receive nonlive vaccinations. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed with secukinumab.8

CYP450 substrates. The formation of cytochrome (CY) P450 enzymes can be altered by elevated levels of certain cytokines during chronic inflammation. Thus, secukinumab, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes. When initiating or discontinuing secukinumab concomitant with CYP450 substrates, consider monitoring for therapeutic effect or drug concentration and consider dosage modification of the CYP450 substrate.8

Warnings and Precautions

Infections. Serious infections have occurred in patients treated with secukinumab. Caution should be exercised when considering secukinumab use in patients with a chronic infection or a history of recurrent infection. If a serious infection develops, secukinumab should be discontinued until the infection resolves.8

Tuberculosis. Before initiating secukinumab treatment, patients should be evaluated for tuberculosis. Secukinumab should not be administered to patients with active tuberculosis infection. In patients with a history of latent or active tuberculosis for whom an adequate course of treatment cannot be confirmed, antituberculosis therapy should be considered prior to initiation of secukinumab. Patients who receive secukinumab should be monitored closely for signs and symptoms of active tuberculosis during and after treatment.8

Crohn’s disease. Caution should be exercised when secukinumab is prescribed to people with active Crohn’s disease, because exacerbations of Crohn’s disease (serious in some cases) were observed in clinical trials. Secukinumab recipients who have active Crohn’s disease should be monitored closely.8

Hypersensitivity reactions. If an anaphylactic reaction or other serious allergic reaction occurs, secukinumab should be discontinued immediately and appropriate therapy initiated.8

Use in Specific Populations

Pregnancy. There are no adequate well-controlled trials of secukin­umab in pregnant women. Secukinumab should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.8

Nursing mothers. It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. Caution should be exercised when secukinumab is administered to a nursing woman.8

Pediatric use. Secukinumab has not been evaluated in pediatric patients.8

Geriatric use. Although no response differences were seen between older and younger patients who received secukinumab, the number of patients aged ≥65 years was not sufficient to determine potential differences.8

Conclusion

The FDA approval of secukinumab, the first IL-17A antagonist for patients with moderate-to-severe plaque psoriasis, marks the availability of a new therapeutic option for this patient population. The safety and effectiveness of secukinumab were demonstrated in 4 clinical trials that included 2403 patients with plaque psoriasis. The clinical response to secukinumab was superior to that of placebo and included clear or almost clear skin. In addition to the clinical benefits demonstrated in these studies, secukinumab, which is available in single-use (Sensoready) pens or prefilled syringes, may provide appropriate patients with convenience and ease of use in managing plaque psoriasis.

References
1. National Psoriasis Foundation. Psoriasis and comorbid conditions issue brief. www.psoriasis.org/document.doc?id=793. Accessed June 10, 2015.
2. Mayo Clinic staff. Diseases and conditions: psoriasis. June 17, 2015. www.mayoclinic.org/diseases-conditions/psoriasis/basics/definition/con-20030838?p=1. Accessed June 10, 2015.
3. National Psoriasis Foundation. About psoriasis: psoriasis severity. www.psoriasis.org/about-psoriasis. Accessed June 10, 2015.
4. National Psoriasis Foundation. Statistics. www.psoriasis.org/cure_known_statistics. Accessed June 11, 2015.
5. National Psoriasis Foundation. Plaque psoriasis. www.psoriasis.org/about-psoriasis/types/plaque. Accessed June 10, 2015.
6. Vanderpuye-Orgle J, Zhao Y, Lu J, et al. Evaluating the economic burden of psoriasis in the United States. J Am Acad Dermatol. 2015;72:961-967.e5.
7. US Food and Drug Administration. FDA approves new psoriasis drug Cosentyx [press release]. January 21, 2015. www.fda.gov/NewsEv ents/Newsroom/PressAnnounce ments/ucm430969.htm. Accessed June 10, 2015.
8. Cosentyx (secukinumab) injection [prescribing information]. East Hanover, NJ: Novartis; January 2015.
9. Novartis. Novartis announces FDA approval for first IL-17A antagonist Cosentyx (secukinumab) for moderate-to-severe plaque psoriasis patients [press release]. January 21, 2015. www.novartis.com/news/media-releases/novartis-announces-fda-approval-first-il-17a-antago nist-cosentyxtm-secukinumab. Accessed June 24, 2015.
10. Langley RG, Elewski BE, Lebwohl M, et al; for the ERASURE and FIXTURE Study Groups. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371:326-338.
11. Blauvelt A, Prinz JC, Gottlieb AB, et al; for the FEATURE Study Group. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172:484-493.
12. Paul C, Lacour JP, Tedremets L, et al; for the JUNCTURE study group. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol. 2015;29:1082-1090.

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Last modified: December 7, 2015
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