Secukinumab (Cosentyx) is a monoclonal antibody introduced for marketing in early 2016. It is indicated for the treatment of plaque psoriasis and separately, ankylosing spondylitis. This column focuses only on the psoriasis indication. Psoriasis arises when the immune system triggers chronic inflammatory reactions affecting the skin.1 This chronic conditions affects approximately 2% to 3% of the Western population.2
A characteristic feature of psoriasis is the appearance of red plaques on the skin. These patches form as a result of rapidly growing new skin cells that push their way to the surface. The elbows, knees, scalp, hands and feet are coated with red and silver scales. These signs are often associated with itching and painful symptoms, and often cause psychological distress.3
In two recent trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis), the objective was to evaluate if secukinumab was superior to placebo after 12 weeks of treatment.4
The studies used a robust trial design, and the FIXTURE trial had an active control.4 The primary endpoint was psoriasis disease activity using the Psoriasis Area and Severity Index (PASI). The aim was to achieve a 75% or more reduction in PASI (PASI 75) and a response of 0 or 1 on the 5-point modified investigator's global assessment at week 12. The global assessment score of 0 to 1 is "clear skin" to "almost clear skin."4
The studies enrolled more than 2,000 patients with moderate to severe plaque psoriasis (mean age 45; 70% men). Sixty-three percent had been treated with conventional agents and biological agents.4
The results showed that the percentage of patients who met PASI 75 criteria in the ERASURE trial was 81.6% with 300 mg secukinumab, 71.6% with 150 mg secukinumab, and 4.5% with placebo (p < 0.001).
The percentage of patients who met PASI 75 criteria in the FIXTURE trial was 77.1% with 300 mg of secukinumab, 67.0% with 150 mg secukinumab, 44.0% with etanercept, and 4.9% with placebo (P < 0.001 for comparisons with etanercept and placebo). The findings based on the investigators' global assessment at week 12 favored the secukinumab group in both trials (p < 0.001 versus etanercept and placebo). Secukinumab was superior over placebo or etanercept, and also had a rapid onset as compared to the etanercept arm.4
Place in Therapy
Generally, mild to moderate psoriasis symptoms are treated with topical medications, targeted biologic agents and phototherapy.
With more extensive disease, the systemic and biologic therapies such as secukinumab may be introduced.5,6 Guidelines have not yet addressed the specific role for secukinumab in therapy.5,6 Prescribers should weigh the risks versus benefits of available options.
Mechanism of Action
A normal immune response to skin cell damage involves cytokine release. Cytokines cause the damaged area to become inflamed and swollen, attracting healing chemicals to repair the damage. In psoriasis, the inflammatory response occurs spontaneously causing unnecessary swelling and buildup of new skin.7 Secukinumab, an antibody, blocks the molecule (interleukin 17A) on T-cells involved in inflammation. This dampens the immune system and prevents plaques from emerging. It is approved for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.7,8
Dosage, Cost & Pharmacokinetics
Secukinumab is given by subcutaneous injection in five weekly 300-mg doses, followed by 300 mg every 4 weeks. The dose is delivered with two injections of 150 mg.9 For some patients, 150 mg may be the most appropriate dose. A 300-mg dose is approximately $4,300.10 Steady state is achieved by week 24, when adhering to the 4-week regimen.9 This drug is widely distributed with a volume of distribution between 7.1 L and 8.6 L. Monoclonal antibodies degrade to small peptides and amino acids. The half-life is 22 to 31 days.
Drug Interactions & Side Effects
Secukinumab suppresses the immune system. Patients taking immunosuppressant drugs (e.g., corticosteroids) are prone to infections.9 Consult a pharmacist to identify potential drug interactions involving immunosuppressant drugs. Live vaccines should not be given to patients who are immunosuppressed.9
The most commonly reported side effects in the trials were nasopharyngitis, headache and diarrhea.4 IL-17 antagonists have been associated with the development of cancer (i.e., cervical carcinoma) and infection.8,9 Other, less common side effects include urticaria, upper respiratory tract infection, rhinitis, rhinorrhea, and oral herpes.8,9 Patients should be instructed to seek medical advice if they experience signs of an infection or exacerbation of Crohn's disease. Secukinumab should be discontinued if hypersensitivity reactions occur.9
Monitor patients for signs and symptoms of an infection, including nasopharyngitis and upper respiratory tract infections. Prior to initiating therapy and periodically during therapy, patients should be screened for tuberculosis. If confirmed, treatment should be discontinued. Hypersensitivity reactions, such as itching at the administration site and anaphylaxis, have been reported.8,9
Sabina Bukowska is a doctor of pharmacy candidate at the University of the Sciences in Philadelphia. Grace Earl is an ambulatory care pharmacist at the University of the Sciences and at Hahnemann University Hospital.
References 1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Questions and Answers about Psoriasis. http://www.niams.nih.gov/Health_Info/Psoriasis/
2. Lonnberg AS, et al. Targeting of interleukin-17 in the treatment of psoriasis. Clin Cosmet Investig Derm. 2014;7:251-259.
3. Mansouri Y, Goldenberg G. New systemic therapies for psoriasis. Cutis. 2015;95(3):155-160.
4. Langley RG, et al. Secukinumab in plaque psoriasis-results of two phase 3 trials. New Engl J Med. 2014;371:326-338.
5. Menter A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2008;58(5):851-864.
6. National Institute for Health and Care Excellence. Psoriasis: the assessment and management of psoriasis. http://www.nice.org.uk/guidance/cg153/chapter/1-recommendations
7. National Psoriasis Foundation. Molecule called IL-17 could unlock more psoriasis treatments. https://www.psoriasis.org/advance/features/interleukin-17-could-unlock-psoriasis-treatments
8. Lexicomp Online, Lexi-Drugs. Secukinumab.
9. Cosentyx (secukinumab) product package insert. 2015.
10. Redbook online. Truven Health Analytics. http://www-micromedexsolutions-com.db.usciences.edu/