New Drug Review 2016

Jack DeRuiter, PhD; Pamela L. Holston, RPh, BS, BA; Taylor Joseph DeRuiter, PharmD


US Pharmacist. 2016;41(10):30-36. 

In This Article

Secukinumab (Cosentyx, Novartis Pharmaceuticals)

Indication and Clinical Profile5,6

Secukinumab has been approved for the treatment of moderate-to-severe plaque psoriasis (Ps) in adults who are candidates for systemic therapy or phototherapy, and also for the treatment of adults with active psoriatic arthritis (PsA) or ankylosing spondylitis (AS). Ps, the most common form of psoriasis, is an autoimmune disorder of the skin characterized by the development of thick, red skin with flaky scales that cause significant skin irritation and discomfort. PsA is a form of inflammatory arthritis that develops in about 30% of people with psoriasis; the inflammation can affect the entire body and cause permanent joint and tissue damage. AS is a chronic disorder characterized by inflammation of the spine and the vertebral and sacroiliac joints.

FDA approval of secukinumab for Ps treatment was based on results of four multicenter, controlled trials in 2,403 adult Ps patients who were candidates for phototherapy or systemic therapy. Efficacy outcomes were the proportion of patients who achieved at least a 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline (PASI75) and treatment success (clear or mostly clear) on the Investigator's Global Assessment (IGA-2011). In all studies, a significantly greater proportion of secukinumab patients versus placebo patients achieved both PASI75 (69% vs. 3%) and clear or mostly clear IGA (67% vs. 1.2%).

Approval of secukinumab for the treatment of PsA was based on results of two randomized, controlled studies (PsA1 and PsA2) involving 1,003 patients aged ≥18 years with active PsA despite nonsteroidal antiinflammatory drug (NSAID), corticosteroid, or diseasemodifying antirheumatic drug (DMARD) therapy. The primary endpoint was the percentage of patients achieving an Assessment in Ankylosing Spondylitis Response Criteria (ASAS20) response at week 24. In PsA1, patients treated with secukinumab 150 mg or 300 mg demonstrated a greater clinical response compared with placebo at week 24 (60% and 57% vs. 18%, respectively).

The efficacy of secukinumab in AS patients was assessed in two controlled studies (AS1 and AS2) involving 590 adult patients aged ≥18 years with active AS despite NSAID, corticosteroid, or DMARD therapy. The primary endpoint was the percentage of patients achieving an ASAS20 response at week 16. At week 16, patients treated with secukinumab 150 mg demonstrated greater improvement in ASAS20 response compared with those given placebo (61% vs. 28%, respectively).

Pharmacology and Pharmacokinetics5,6

Secukinumab is a human immunoglobulin G1 (IgG1) monoclonal antibody that binds selectively to the interleukin-17A (IL-17A) cytokine, blocking IL-17A from activating its receptor and effectively inhibiting the cytokine's ability to trigger the inflammatory response.

The absolute bioavailability of secukinumab ranges from 55% to 77%. Secukinumab achieves peak serum concentration in approximately 6 days and reaches steady state by week 24 of regular dosing. It has a volume of distribution of 7 L to 8 L and is thought to be metabolized to small peptides via catabolic pathways analogous to endogenous IgG. The mean half-life of secukinumab is 22 to 31 days, and the drug is cleared at a rate of 0.14 L to 0.22 L per day.

Adverse Reactions and Drug Interactions5,6

The most common adverse reactions reported during clinical trials of secukinumab included nasopharyngitis, diarrhea, and upper respiratory tract infection. The drug carries warnings regarding an increased risk of infection, including tuberculosis (patients should be tested for tuberculosis prior to initiation); an increased risk of exacerbation in patients with Crohn's disease; and a general warning regarding anaphylaxis. Secukinumab may be used during pregnancy only if the potential benefit justifies the potential harm to the fetus. It is not known whether secukinumab is excreted in breast milk.

Owing to the increased risk of infection, patients taking secukinumab should not receive live vaccinations. Although there is no reported role for IL-17A in the regulation of CYP enzymes, the formation of these enzymes is altered during chronic inflammation and therefore could be normalized by secukinumab. Because of this potential for interaction, monitoring is advised upon secukinumab initiation or discontinuation in patients who are currently taking other drugs that are CYP substrates and have a narrow therapeutic index.

Dosage and Administration5,6

Secukinumab is supplied as single-use, 150 mg/mL prefilled syringes or Sensoready pens and as 150 mg lyophilized powder in a single-use vial (for healthcare providers only). The recommended dosage for Ps is 300 mg by SC injection at weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Each 300-mg dose is given as two injections of 150 mg. This regimen is recommended for PsA patients with coexistent moderate-to-severe Ps. In other PsA patients or those with AS, secukinumab may be administered with or without a loading dose (LD). The recommended dosage with an LD is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. Dosing without an LD is 150 mg every 4 weeks, possibly increasing to 300 mg if a patient continues to have active PsA. No dose adjustments are required in patients with renal or hepatic impairment or in elderly patients. Secukinumab has not been studied in pediatric patients.