• Home
  • Dupilumab (Dupixent) Use in Asthma

Dupilumab (Dupixent) Use in Asthma

16 May 2019 11:50 AM | Deleted user

Author:  Shannon Mensing, 2019 PharmD Candidate
St. Louis College of Pharmacy

Mentor: Jennifer Rushing, PharmD
Clinical Pharmacist, SSM Health St. Joseph Hospital – St. Charles

According to the Center for Disease Control, more than 26 million Americans suffer from asthma, accounting for approximately 8% of children and 8% of adults. Within this population, 5 to 10% of patients have severe asthma that does not respond to conventional therapy with a short-acting beta-agonist and inhaled corticosteroids. Patients with refractory asthma experience an increased rate of exacerbations, hospital visits, and medical costs.1 In recent years, monoclonal antibodies have been approved in addition to the standards of care in asthma to treat these patients with type 2 inflammation. Recently, dupilumab (Dupixent) was approved by the FDA to treat for add-on maintenance treatment of patients 12 years or older with moderate to severe asthma with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.3

Dupilumab (Dupixent), manufactured by Regeneron Pharmaceuticals and Sanofi, was originally approved in March of 2017 with an FDA approval to treat adults with moderate to severe atopic dermatitis that is not adequately controlled with topical therapy. It was hypothesized that dupilumab may have a beneficial and therapeutic value in the treatment of asthma after it was found to treat other conditions that are driven by type 2 inflammation, including the aforementioned atopic dermatitis and chronic sinusitis, both of which are commonly found in patients with asthma. After further investigation, it confirmed that dupilumab had a beneficial effect in asthma as well. Currently there are other monoclonal antibodies on the market used to treat asthma that target the IL-5 cytokine pathway. Dupilumab has a different mechanism of action that targets a separate pathway of inflammation by blocking IL-4 and IL-13 pathways, inhibiting type 2 inflammation.2

Three major clinical trials were published that contributed to approval of dupilumab in the treatment of asthma. All were double-blind, randomized, placebo-controlled trials. In a phase 2b dosing trial published in 2016, adult patients with uncontrolled persistent asthma on guideline directed medical therapy were assigned to treatment with dupilumab or placebo. The primary endpoint of the trial was change from baseline at week 12 in forced expiratory volume in 1 second (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per microliter. Dupilumab was found to have the greatest effect in the population with a baseline eosinophil count greater than 300. However, there was a benefit seen in the general population in both improved FEV1 and decreased rates of exacerbations.  Both treatment groups that received the 200 and 300 mg doses had a mean improvement of approximately 0.40 L in FEV1 at 12 weeks when compared to placebo.  Additionally, patients treated with dupilumab also saw a reduction of up to 70% in the rates of annual severe exacerbations.5

Another trial looked at patients 12 years of age or older with moderate to severe asthma treated with inhaled corticosteroid and long-acting beta-agonist combination products with moderate to severe uncontrolled asthma. Patients again were assigned to treatment groups with either 200 or 300 mg of dupilumab or matching placebos. Treatment with dupilumab when compared to placebo showed a significant reduction in annualized rates of severe asthma exacerbations with the most benefit in patients with elevated baseline eosinophil counts. Patients in the 200 mg treatment group had an annualized asthma exacerbation rate of 0.46, compared to 0.87 in the placebo group. It also resulted in improved lung function and asthma control, measured by FEV1.  At 12 weeks of treatment, the treatment group that received the lower dose of dupilumab experienced a 0.32 L increase in FEV1 with similar effects noted with the 300 mg dose as well. 4

A third trial used to garner approval for dupilumab treatment in asthma looked at asthmatic patients dependent on oral glucocorticoids at the time of randomization. The trial’s primary outcome analyzed the percentage of glucocorticoid reduction at week 24 of therapy compared to placebo. Patients in the population treated with dupilumab saw a reduction in use of oral glucocorticoids, in addition to an improvement in FEV1 and a reduction in rates of exacerbations. The treatment group saw a percentage decrease in glucocorticoid use of approximately 70% with a 0.22 L increase in FEV1.  Treatment with dupilumab also resulted in a 59% lower rate of severe exacerbations when compared with placebo.6 

Each trial showed a benefit with the use of dupilumab in the treatment of asthma. Both initial trials reduced the annual rate of asthma exacerbations per year in the trial population.4,5  Additionally, the oral glucocorticoid dependent group saw a mean reduction of approximately 70% in the dose of oral steroids they were receiving.6 Dupilumab was shown to have greatest effects in the population subgroup that had an eosinophil count 300.4,5Among these three trials, similar adverse reactions were observed. Injection site reactions and a transient rise in eosinophils were the two most common reactions associated with treatment.4-6

Dupilumab dosing is determined based on the severity of disease. Patients with moderate-to-severe asthma are initially treated with a 400 or 600 mg loading dose divided into 2 equal subcutaneous injections via a prefilled syringe, followed by a maintenance dose of 200 mg or 300 mg every 2 weeks, respectively. Patients with oral glucocorticoid dependent disease are treated with a 600 mg loading dose divided into two equal subcutaneous injections, followed by 300 mg given every 2 weeks. Patients may self-administer this medication at home following training by a healthcare provider. When injecting the medications, patient should be instructed to keep the syringe capped and allow the solution to reach room temperature for 30 to 45 minutes prior to use.3

As with many other biologic agents, cost of the medication may be a limiting factor in the utilization. Estimated average wholesale price for the 200 mg pre-filled syringe is around $1,589.8  However, dupilumab has shown promising results in the treatment of asthma, especially those with elevated eosinophil counts. It can be considered in patients after maximum use of conventional therapy with inhalers and may provide relief in patients that have exhausted other options.

References

  1. Asthma Facts and Figures. Asthma. https://www.aafa.org/asthma-facts/. Published February 2018. Accessed April 23, 2019.
  2. Office of the Commissioner. Press Announcements - FDA approves new eczema drug Dupixent. U S Food and Drug Administration Home Page. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm549078.htm. Published March 28, 2017. Accessed April 23, 2019.
  3. Dupilumab (Dupixent) for Asthma. The Medical Letter. https://secure.medicalletter.org/w1563c. Published January 14, 2019. Accessed April 23, 2019.
  4. Castro M, Corren J, Pavord I. et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. New England Journal of Medicine. 2018;378:2486-2496. doi:10.1056/NEJMoa1804092
  5. Wenzel S, Castro M, Corren J. et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. The Lancet. 2016;388(10039):31-48. doi:S0140-6736(16)30307-5
  6. Rade K, Nair P, Brusselle G. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. New England Journal of Medicine. 2018;378:2475-2485. doi:10.1056/NEJMoa1804093
  7. Dupilumab. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.  Available at:  http://online.lexi.com . Accessed April 26, 2019


Upcoming events


Copyright 2020, Missouri Society of Health-System Pharmacists
501(c)6 non-profit organization. 2650 S. Hanley Rd., Suite 100, St. Louis, MO 63144 
p: (314) 416-2246, f: (314) 845-1891, www.moshp.org
Powered by Wild Apricot Membership Software