By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco
Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
A recombinant, fully humanized monoclonal antibody to interleukin-17 has been approved for the treatment of moderate-to-severe plaque psoriasis. Secukinumab is marketed by Novartis as Cosentyx™.
INDICATIONS
Secukinumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.1
DOSAGE
The recommended dose is 300 mg (two injections) given subcutaneously weekly for five doses (week 0, 1, 2, 3, and 4). This is followed by 300 mg every 4 weeks.1 Some patients may only require 150 mg per dose. Secukinumab is available as a single-use 150 mg Senso-ready pen or prefilled syringe for self injection. It is also available as single-use (150 mg) lyophilized powder for health care professional use.
POTENTIAL ADVANTAGES
Secukinumab targets a different cytokine in the pathogenesis of psoriasis.2
POTENTIAL DISADVANTAGES
Increased infection rates have been associated with secukinumab treatment.1,2 Most common adverse events reported were nasopharyngits, diarrhea, and upper respiratory tract infections.1 These ranged from 3-12%.
COMMENTS
The safety and efficacy of secukinumab were evaluated in four clinical trials.1,3,4 These adult participants (n = 2403) had plaque psoriasis (minimum 10% body surface involvement and Psoriasis Area and Severity Index [PASI] ≥ 12) and were candidates for phototherapy or systemic therapy. Patients were randomized to secukinumab 150 mg, 300 mg, an active control, or placebo.1,2 Secukinumab was administered at weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks. The active control was etanercept 50 mg twice weekly for 12 weeks, then once weekly to week 51. Two trials were 12 weeks in duration and two were 52 weeks, with assessment at 12 weeks.
The primary endpoints were proportion of participants who achieved a reduction in PASI of at least 75% (PASI75), and treatment success was based on the modified Investigator’s Global Assessment (IGA). PASI is a composite instrument for psoriasis severity (i.e., erythema, induration, scaling, and percent body-surface affected). IGA is a 5-point clinician assessment of overall disease severity (0 = clear, 1 = almost clear, 4 = severe). PASI75 at week 12 for the four studies ranged from 67-71% for secukinumab 150 mg, 75-87% for 300 mg, and 0-5% for placebo. IGA for clear or almost clear ranged from 51-53% for 150 mg, 62-73% for 300 mg, and 0-3% for placebo. Eighty-one percent to 84% of responders at week 12 maintained PASI75 for 52 weeks on 300 mg and 72-82% on 150 mg. The percentage maintaining IGA of clear or almost clear were 74-80% and 59-68%, respectively. In the study with an active control, etanercept, PASI75 was 44% and IGA 27%. The median times for 50% reduction of baseline PASI score was 3 weeks for the 300 mg dose and 3.9 weeks for the 150 mg dose vs 7 weeks for etanercept. The adverse drug reaction profiles were similar between secukinumab and etanercept;3 however, Candida infections were more frequent with secukinumab (2.3-4.7%) compared to 1.2% for etanercept.3
CLINICAL IMPLICATIONS
Secukinumab is the first in the class monoclonal antibody to interleukin-17A, which is regarded as an important cytokine in the pathogenesis of psoriasis.2,4 Previous drugs have targeted TNF and IL23. Secukinumab provides another effective treatment for plaque psoriasis. It appears to be more effective than etanercept but similar in magnitude to other biological agents (e.g., adalinumab and ustekinumab.6,7 The wholesale cost is $3420 per 300 mg dose.
REFERENCES
1. Cosentyx Prescribing Information. Novartis Pharmaceuticals. January 2015.
2. Kirham BW et al. Immunology 2013;141:133-42.
3. Langley RG et al. Secukinumab in plaque psoriasis — results of two phase 3 trials. N Engl J Med 2014;37:326-338.
4. Blauvelt A et al. Secukinumab administration by pre-filled syringe: Efficacy, safety and usability results from a randomized controlled trial in psoriasis. Br J Dermatol 2014;172:484-493.
5. Martin DA et al. The emerging role of IL-17 in the pathogenesis of psoriasis: Preclinical and clinical findings J Invest Dermatol 2013;133:17-26.
6. Humira Prescribing Information. AbbVie Inc. December 2014.
7. Stelare Prescribing Information. Janssen Biotech. March 2014.
A recombinant, fully humanized monoclonal antibody to interleukin-17 has been approved for the treatment of moderate-to-severe plaque psoriasis. Secukinumab is marketed by Novartis as Cosentyx.
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