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Targeting Interleukin-5 in Patients With Severe Eosinophilic Asthma: A Clinical Review

Christine Lam PharmD, BCPS
Kunal J. Shah PharmD
Rupal Mansukhani PharmD

INTRODUCTION

Asthma is a chronic lung disease characterized by inflammation and narrowing of the airways, which results in periods of wheezing, chest tightness, shortness of breath, and coughing.1 It is believed that genetic and environmental factors interact to cause the disease, usually early in life. These factors include atopy (an inherited tendency to develop allergies); parents who have asthma; and certain respiratory infections during childhood.2 An estimated 17.7 million adults and 6.3 million children in the United States have asthma.3 According to statistics from the Centers for Disease Control and Prevention, 50% of adults (18 years of age and older) and 38% of children (younger than 18 years of age) with asthma had uncontrolled disease in 2006–2010.4 In 2011, an estimated 1.8 million emergency department visits had asthma as the primary diagnosis.3

Severe asthma is defined as disease that requires treatment with high-dose inhaled glucocorticoids plus a second controller and/or systemic glucocorticoids to prevent asthma from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy.5

Eosinophilic asthma is an important subtype of asthma characterized by increased levels of eosinophils (a type of white blood cell) in sputum, increased disease severity, late onset, and corticosteroid refractoriness.68 Interleukin-5 (IL-5) is known to play a major role in promoting the growth, differentiation, recruitment, and activation of eosinophils in tissues.9,10 Therefore, targeting IL-5 was identified as a potential treatment approach for patients with eosinophilic asthma.6

The Food and Drug Administration (FDA) has approved mepolizumab (Nucala, GlaxoSmithKline) and reslizumab (Cinqair, Teva Pharmaceuticals) for the treatment of patients with severe asthma with an eosinophilic phenotype. Both medications are IL-5 antagonist monoclonal antibodies produced by recombinant DNA technology. Mepolizumab was approved in November 2015 for use in children and adults (12 years of age and older), and reslizumab was approved in March 2016 for use only in adults (18 years of age and older).1114

This article reviews the efficacy and safety of mepolizumab and reslizumab in patients with severe eosinophilic asthma.

MEPOLIZUMAB

Mepolizumab is indicated for the add-on maintenance treatment of both pediatric and adult patients (12 years of age and older) with severe asthma and with an eosinophilic phenotype. The drug is administered into the upper arm, thigh, or abdomen as a 100-mg subcutaneous (SC) injection once every four weeks. It is available as a lyophilized powder in a single-dose vial for reconstitution. Mepolizumab binds to IL-5, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. Following SC injection, mepolizumab has approximately 80% bioavailability and a mean terminal half-life of 16 to 22 days.13

Mepolizumab was compared with placebo as an add-on to standard-of-care therapy in three pivotal trials involving patients with severe eosinophilic asthma (Table 1). These studies are discussed below.

Pavord et al. (2012)15

Pavord and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study (DREAM) to determine the efficacy and safety of mepolizumab in patients with a history of recurrent severe asthma exacerbations and signs of eosinophilic inflammation. A total of 621 patients (12 to 74 years of age) were enrolled in the study. Each patient had a history of two or more asthma exacerbations requiring treatment with systemic glucocorticoids during the previous year.

The patients were randomly assigned to receive one of three doses of intravenous (IV) mepolizumab—75 mg (n = 154), 250 mg (n = 152), or 750 mg (n = 156)—or placebo (n = 159) every four weeks for 52 weeks in addition to standard therapy. The study’s primary endpoint was the mean annualized rate of clinically significant exacerbations (defined as worsening of asthma requiring the use of oral glucocorticoids for three or more days; hospital admission; or an emergency department visit). Secondary outcomes included changes in the baseline forced expiratory volume in one second (FEV1); changes in responses to the Asthma Control Questionnaire (ACQ) and to the Asthma Quality of Life Questionnaire (AQLQ); and blood eosinophil counts.

The rates of clinically significant exacerbations were 2.40 per patient per year for placebo; 1.24 for mepolizumab 75 mg (48% reduction; P < 0.0001); 1.46 for mepolizumab 250 mg (39% reduction; P = 0.0005); and 1.15 for mepolizumab 750 mg (52% reduction; P < 0.0001).

Blood eosinophil counts were significantly lower in all of the mepolizumab groups compared with placebo (P < 0.0001). Mepolizumab also increased the FEV1 compared with placebo, but the differences were not statistically significant. Changes in ACQ and AQLQ measures were similar among the treatment groups.

Mepolizumab was well tolerated. The most common adverse events included respiratory, thoracic, and mediastinal disorders. Three patients died during the study, but the deaths were not considered to be related to therapy.

The investigators concluded that mepolizumab is an effective and well-tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. It is important to note, however, that mepolizumab was administered intravenously in this study, whereas the drug is currently approved only for SC administration. Moreover, although the mean annualized rate of clinically significant exacerbations was significantly reduced in all of the mepolizumab groups compared with placebo, the rate of exacerbations requiring hospital admission was reduced only in the 750-mg arm.

Ortega et al. (2014)16

Ortega and colleagues conducted a randomized, double-blind, double-dummy study (MENSA) to confirm the ability of mepolizumab to reduce exacerbation rates in patients with recurrent exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled corticosteroids.

A total of 576 patients (12 to 82 years of age) were randomly assigned to one of three treatment arms: mepolizumab 75 mg IV (n = 191); mepolizumab 100 mg SC (n = 194); or placebo (n = 191). The treatments were administered every four weeks for 32 weeks. The patients were allowed to continue their current antiasthma therapies. The primary outcome was the mean annualized rate of clinically significant exacerbations per patient-year. Secondary outcomes included changes in blood eosinophil counts from baseline; changes in the ACQ score and in the St. George’s Respiratory Questionnaire (SGRQ); and the presence of antimepolizumab antibodies.

The mean annualized rates of clinically significant exacerbations were 1.74 for placebo; 0.93 for IV mepolizumab (47% reduction; P < 0.001); and 0.83 for SC mepolizumab (53% reduction; P < 0.001). The mean rate of exacerbations requiring hospitalization was significantly lower in both mepolizumab groups compared with placebo (P = 0.03). However, the rate of emergency department visits and hospitalizations was significantly lower for the SC mepolizumab group (P = 0.02) but not for IV mepolizumab (P = 0.30).

At the end of the 32-week study, the mean changes in FEV1 from baseline were 186 mL in the IV mepolizumab group (P = 0.02) and 183 mL in the SC mepolizumab group (P = 0.03) compared with 60 mL in the placebo group. The improvements in ACQ and SGRQ scores were also statistically significant for the two mepolizumab groups compared with placebo (P < 0.001) (Table 1). Blood eosinophil counts were reduced by 83% with IV mepolizumab and by 86% with SC mepolizumab compared with baseline.

The most common adverse events associated with IV mepolizumab, SC mepolizumab, and placebo included nasopharyngitis (24%, 17%, and 24%, respectively); headache (24%, 20%, and 17%); and upper respiratory tract infection (12%, 12%, and 14%). Nineteen mepolizumab-treated patients (4.9%) had antimepolizumab antibodies; none was a neutralizing antibody.

The authors concluded that both IV and SC mepolizumab, administered in addition to the patients’ current antiasthma treatments, significantly reduced asthma exacerbations and were associated with improvements in markers of asthma control.

This study is significant in that it analyzed mepolizumab 100 mg SC, which is currently the medication’s only FDA-approved dose and route of administration. The 100-mg dose reduced both the rate of clinically significant exacerbations and the rate of exacerbations requiring hospitalization. In comparison, the 75-mg IV dose reduced only the rate of clinically significant exacerbations.

Bel et al. (2014)17

Bel and colleagues conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy of mepolizumab in reducing the use of maintenance oral glucocorticoids while maintaining asthma control in patients with severe eosinophilic asthma.

Patients were eligible for the study if they had at least a six-month history of maintenance treatment with systemic glucocorticoids before enrollment. They also had to have eosinophilic inflammation, defined as a blood eosinophil level of at least 300 cells/mcL during the 12-month period before screening or at least 150 cells/mcL during the optimization phase. All of the patients were treated with high-dose inhaled glucocorticoids and an additional controller.

The study was divided into three phases. Once the patients’ oral corticosteroid dose had been optimized, 135 patients were randomly assigned to receive either mepolizumab 100 mg SC (n = 69) or placebo (n = 66) during the induction phase (weeks 0 to 4). This was followed by a reduction phase (weeks 4 to 20), which was designed to reduce patients’ glucocorticoid doses according to a prespecified schedule. During the maintenance phase (weeks 20 to 24), no further adjustment was made in the oral glucocorticoid dose. The trial’s primary outcome was the percentage reduction in the oral glucocorticoid dose at 20 to 24 weeks compared with the dose determined during the optimization phase. Secondary outcomes included the annualized rate of asthma exacerbations, the mean change in FEV1 from baseline, ACQ scores, SGRQ scores, and immunogenicity.

The primary outcome occurred more often in the mepolizumab group than in the placebo group (odds ratio, 2.39; P = 0.008). More mepolizumab-treated patients than placebo-treated patients had a reduction of 90% to 100% in the oral glucocorticoid dose (23% versus 11%, respectively) and a reduction of 70% to less than 90% (17% versus 8%). The median percent reduction from baseline in the daily glucocorticoid dose was 50% in the mepolizumab group compared with 0% in the placebo group (P = 0.007). The annual rate of exacerbation was also significantly lower in the mepolizumab group (1.44 per year) compared with the placebo group (2.12 per year; P = 0.04). Mepolizumab-treated patients showed significant improvements compared with placebo-treated patients in ACQ scores (−0.52 points; P = 0.004) and in SGRQ scores (−5.8 points; P = 0.02) at 24 weeks. There was no significant difference in the change in FEV1 from baseline between the two groups.

The most common adverse events were headache (20% for mepolizumab versus 21% for placebo) and nasopharyngitis (14% versus 15%). Of the 135 patients in the study, six (4.4%) developed antimepolizumab antibodies; one of these patients had neutralizing antibodies.

This study thus demonstrated the significant glucocorticoid-sparing effect of the approved dose of mepolizumab (100 mg SC) in patients requiring daily oral glucocorticoid therapy to maintain asthma control. Mepolizumab also reduced exacerbations and improved the control of asthma symptoms.

Use in Specific Populations13

Data on pregnancy exposure from clinic trials are insufficient to delineate the pregnancy risk of mepolizumab. Moreover, there is no information regarding the presence of mepolizumab in human milk, the effects on breastfed infants, or the effects on milk production.

The safety and efficacy of mepolizumab in pediatric patients (younger than 12 years of age) have not been established, and it is not known whether older patients (65 years of age and older) respond differently than younger subjects.

Mepolizumab is not cleared renally; therefore, no clinical trials have investigated the effects of renal impairment on the drug’s pharmacokinetics. Similarly, no clinical studies have been conducted to investigate the effect of hepatic impairment on the pharmacokinetics of mepolizumab. Because mepolizumab is degraded by enzymes that are not restricted to hepatic tissue, changes in hepatic function are unlikely to have an effect on the drug’s elimination. No formal drug interaction studies have been conducted with mepolizumab.

Cost

The average wholesale price (AWP) for one 100-mg vial of mepolizumab is $3,214.18

RESLIZUMAB

Reslizumab is indicated for the add-on maintenance treatment of adults (18 years of age and older) with severe asthma and an eosinophilic phenotype. The recommended dosing regimen is 3 mg/kg administered by IV infusion over 20 to 50 minutes once every four weeks. The medication is supplied in 100 mg/10 mL (10 mg/mL) single-use vials. Reslizumab binds to IL-5, thereby blocking the bioactivity of IL-5 by preventing its binding to the alpha chain of the IL-5 receptor complex expressed on the surface of eosinophils. It has an elimination half-life of approximately 24 days.14

Reslizumab was evaluated in four pivotal, placebo-controlled trials as an add-on to standard of care in patients with severe eosinophilic asthma (Table 2).

Castro et al. (2015)1921

Castro and colleagues conducted two duplicate phase 3, double-blind, parallel-group, placebo-controlled studies of reslizumab in a total of 995 pediatric and adult patients (12 to 75 years of age) with severe eosinophilic asthma. While patients ages 12 to 17 years were included in these studies, reslizumab is not approved for this age group.19,20

In the first study, 433 patients with asthma and blood eosinophil counts greater than or equal to 400 cells/mcL were randomly assigned to receive double-blind treatment with IV reslizumab (3.0 mg/kg; n = 218) or placebo (n = 215). Both treatments were administered once every four weeks for a total of 13 doses. The study had two primary outcomes—the frequency of clinical asthma exacerbations (CAEs) during 12 months of treatment and the frequency of each of the two criteria for CAEs defined as:

  • The use of systemic, or an increase in the use of inhaled, corticosteroid treatment for three or more days; or a twofold or greater increase for at least three days for patients already using corticosteroids.
  • Asthma-related emergency treatment, such as an unscheduled visit to the physician’s office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization.

The patients’ mean age was 47 years; 63% were female; and 73% were white.19,20

The asthma exacerbation rates during 12 months of treatment were 0.90 for reslizumab and 1.80 for placebo (P < 0.0001).19,20

The frequency of exacerbations requiring systemic corticosteroid use for more than three days was significantly lower with reslizumab compared with placebo (0.72 versus 1.60, respectively; P < 0.0001). Similarly, the frequency of exacerbations requiring hospitalization or an emergency room visit was 0.14 for reslizumab and 0.21 for placebo (P < 0.0001).19,20

Safety evaluations were conducted from day 1 (post-dose) to day 65. Thirty-six patients experienced a treatment-related adverse event (AE) in each treatment group (14.7% for reslizumab and 14.8% for placebo). Four patients (1.6%) in the reslizumab arm and eight patients (3.3%) in the placebo arm experienced AEs that led to discontinuation. There was one death in the placebo group.20

In the second study, 464 patients with asthma and blood eosinophil counts greater than or equal to 400 cells/mcL were randomly assigned to receive double-blind treatment with IV reslizumab (3.0 mg/kg; n = 232) or placebo (n = 232). Both treatments were administered once every four weeks for a total of 13 doses. Like the first study, the trial had two primary outcomes: the frequency of CAEs during 12 months of treatment and the frequency of each of the two criteria for CAEs. The patients’ mean age was 47 years; 63% were female; and 73% were white.19,21

The asthma exacerbation rates during 12 months of treatment were 0.86 for reslizumab and 2.12 for placebo (P < 0.0001).19,21

The frequency of exacerbations requiring systemic corticosteroid use for more than three days was also significantly lower with reslizumab compared with placebo (0.65 versus 1.66, respectively; P < 0.0001). Moreover, the frequency of exacerbations requiring hospitalization or an emergency room visit was 0.03 for reslizumab and 0.05 for placebo (P < 0.0001).19,21

Safety evaluations were conducted from day 1 (post-dose) to day 65. Thirty-four patients (14.6%) experienced a treatment-emergent AE in the reslizumab group, and 27 patients (11.6%) experienced a treatment-emergent AE in the placebo group. Eight patients in the reslizumab arm (1.6%) and nine patients (3.9%) in the placebo arm experienced AEs that led to discontinuation. There were no deaths in either group.21

Overall, these studies demonstrated that IV reslizumab reduces the annual frequency of asthma exacerbation in patients with severe eosinophilic asthma. Reslizumab was safe and effective throughout the studies’ 12-month treatment periods.

Bjermer et al. (2016)22

Bjermer and colleagues conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study to determine the efficacy and safety of reslizumab in 315 patients 12 to 75 years of age with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid and with a blood eosinophil count greater than or equal to 400 cells/mcL. The patients were randomly assigned to receive IV reslizumab 0.3 mg/kg, IV reslizumab 3.0 mg/kg, or placebo once every four weeks for 16 weeks for a total of four doses. The primary efficacy outcome was the change in prebronchodilator FEV1 during the study period. Secondary endpoints included forced vital capacity (FVC); forced expiratory flow at 25% to 75% of FVC (FEF25–75); patient-reported control of asthma symptoms; short-acting beta agonist (SABA) use; blood eosinophil levels; and safety.

FEV1 improved significantly after 16 weeks of treatment with IV reslizumab 3.0 mg/kg (286 mL; P = 0.0018) and IV reslizumab 0.3 mg/kg (242 mL; P = 0.0237) compared with placebo (126 mL). Improvement in FEV1 was seen as early as four weeks with the higher dose. Reslizumab 3.0 mg/kg also produced substantial improvements in FVC (treatment difference, 130 mL) and FEF25–75 (treatment difference, 233 mL/s) compared with placebo during the 16-week treatment period; negligible or no improvements in these parameters were observed for reslizumab 0.3 mg/kg. Both reslizumab doses improved asthma symptoms and reduced blood eosinophil levels.

The most common AEs in the reslizumab groups included asthma, headache, nasopharyngitis, upper respiratory tract infection, and sinusitis.

Overall, this study demonstrated that IV reslizumab improves lung function in patients with eosinophilic asthma compared with placebo. The 3.0-mg/kg dose appeared to provide greater improvements in asthma outcomes compared with the 0.3-mg/kg dose, with comparable safety.

Corren et al. (2016)23

Corren and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of reslizumab in patients with poorly controlled asthma, with a focus on patients with eosinophil levels of less than 400 cells/mcL. The study consisted of a three-week screening period; a 16-week double-blind treatment period; and a 12-week follow-up period. A total of 422 patients completed treatment with IV reslizumab 3.0 mg/kg (n = 340) or IV placebo (n = 82), administered once every four weeks for a total of four doses. The primary endpoint was the change in FEV1 from baseline to week 16. Secondary endpoints included the ACQ-7 score; rescue SABA use within the previous three days; FVC; and blood eosinophils.

There was no significant difference in the primary outcome between the reslizumab and placebo groups. The mean change in FEV1 from baseline to week 16 was 255 mL for reslizumab and 187 mL for placebo, with a between-group difference of 68 mL (P = 0.17). The investigators determined that 80% of the study population had blood eosinophil counts of less than 400 cells/mcL at randomization. In this subgroup, the difference in the change in FEV1 from baseline to week 16 between reslizumab-treated (n = 275) and placebo-treated (n = 68) patients was 33 mL (P = 0.54). In the patients with eosinophil counts greater than or equal to 400/mcL, the difference in the change in FEV1 between the reslizumab (n = 69) and placebo (n = 13) groups was 270 mL (P = 0.04). Compared with placebo, reslizumab provided modest improvements in ACQ-7, SABA use, and FVC. A marked reduction in blood eosinophils was observed after the first dose of reslizumab compared with placebo, and this difference was maintained during the 16 weeks of treatment (overall treatment difference, −260 cells/mcL; P < 0.0001).

The most common AEs in the reslizumab group included asthma, upper respiratory tract infection, and sinusitis.

This study demonstrated that IV reslizumab was more beneficial than placebo in improving disease outcomes in patients with asthma that was inadequately controlled on a medium-to-high-dose inhaled corticosteroid-based regimen. Reslizumab did not improve lung function or measures of symptom control in patients with blood eosinophil counts of less than 400 cells/mcL. It is important to note that the study was not adequately powered to test the efficacy of reslizumab across multiple eosinophil subgroups. Moreover, the authors noted that the magnitude of the treatment difference between reslizumab and placebo in the subgroup with eosinophil counts greater than or equal to 400 cells/mcL appeared to have been primarily influenced by a near complete lack of response in the small number of patients treated with placebo.

Use in Specific Populations14

The clinical studies of reslizumab do not provide sufficient data to determine whether the drug poses a risk during pregnancy. Moreover, it is not known whether reslizumab is present in human milk, and the effects of reslizumab on breastfed infants and on milk production are not known.

Reslizumab is not indicated for use in patients younger than 18 years of age. The safety and efficacy of reslizumab in this population have not been established.

Reslizumab has been evaluated in a total of 122 patients 65 years of age and older with asthma. No overall differences in safety or efficacy were observed between these patients and younger patients. Based on the available data, no dosage adjustments are necessary in geriatric patients.

No clinical studies have been conducted to assess the effects of renal or hepatic impairment on the pharmcokinetics of reslizumab.

Cost

The AWP for one 100-mg/10-mL vial of reslizumab is $1,002.18

DISCUSSION

Both mepolizumab and reslizumab are approved as add-on therapies for the treatment of patients with severe eosinophilic asthma. Mepolizumab has been evaluated in three pivotal studies,1517 but only two used the FDA-approved dose (100 mg SC).16,17 In one study, this dose was found to reduce emergency room visits and hospitalizations.16 Mepolizumab also demonstrated a significantly greater reduction in the required maintenance dose of oral glucocorticoids compared with placebo.17

Reslizumab has been studied in four pivotal trials,1923 all of which evaluated the FDA-approved dose (3 mg/kg IV). All of the studies reported improvements in FEV1,1923 and one noted a general reduction in exacerbations.19,20 None of the studies, however, examined exacerbations that led to emergency room visits or hospitalizations. All of the reslizumab trials were relatively short (16 weeks)1923 compared with the mepolizumab studies (24, 32, and 52 weeks).1517

When comparing the costs of these medications, the patient’s weight is an important consideration. In patients weighing less than 66.7 kg, reslizumab is less expensive. The recommended dose of 3 mg/kg equates to 200 mg at 66.7 kg, which requires two vials of the medication at an AWP of $2,004. However, in patients weighing more than 66.7 kg (which includes the average adult man or woman), three vials of reslizumab are required (with the excess discarded, per the manufacturer), at a cost of $3,006.14,18 The AWP of a dose of mepolizumab is approximately $200 higher—$3,214—regardless of weight. For a man or woman of average weight, the annual costs of treatment would be $41,782 for mepolizumab and $39,078 for reslizumab.18 In addition, mepolizumab is given as a SC injection, 13 whereas reslizumab is an IV infusion.14 Clinicians must therefore consider administration costs and the potential risks associated with IV therapy. Overall, mepolizumab appears to be the preferred treatment because it has been shown to reduce steroid requirements, to reduce hospitalization rates, and to require less-invasive administration.

CONCLUSION

The anti–IL-5 medications mepolizumab and reslizumab provide valuable options for clinicians who are treating patients with severe eosinophilic asthma. The ability of these medications to reduce the production and survival of eosinophils improves the control of asthma exacerbations, increases FEV1, and improves patients’ quality of life.

Tables

Primary Efficacy Endpoints in Pivotal Studies of Mepolizumab in Patients With Severe Eosinophilic Asthma1517

Study Study Design Regimens Primary Efficacy Endpoint
Pavord et al. (2012) Multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in 621 patients
  • MEP 75 mg IV (n = 154)
  • MEP 250 mg IV (n = 152)
  • MEP 750 mg IV (n = 156)
  • Placebo (n = 159)
Administered once every four weeks for 52 weeks for total of 13 infusions
Mean annualized rate of clinically significant exacerbations

    Results:

  • ○ MEP 75: 1.24*
  • ○ MEP 250: 1.46*
  • ○ MEP 750: 1.15*
  • ○ Placebo: 2.40
Ortega et al. (2014) Multicenter, randomized, double-blind, double-dummy trial in 576 patients
  • MEP 75 mg IV (n = 191)
  • MEP 100 mg SC (n = 194)
  • Placebo (n = 191)
Administered every four weeks for 32 weeks; patients continued current antiasthma therapies
Mean annualized rate of clinically significant exacerbations

    Results:

  • ○ MEP IV: 0.93*
  • ○ MEP SC: 0.83*
  • ○ Placebo: 1.74
Bel et al. (2014) Multicenter, randomized, double-blind, placebo-controlled trial in 135 patients Induction phase (0–4 weeks); reduction phase (4–20 weeks); and maintenance phase (20–24 weeks)
  • MEP 100 mg SC (n = 69)
  • Placebo (n = 66)
Percentage reduction in oral glucocorticoid dose at 20–24 weeks

    Results (90% to 100% reduction):

  • ○ MEP SC: 23%*
  • ○ Placebo: 11%

Results (70% to < 90% reduction):

  • ○ MEP SC: 17%*
  • ○ Placebo: 8%
  • IV = intravenous; MEP = mepolizumab; SC = subcutaneous.

    *Statistically significant improvement with MEP compared with placebo

    Exacerbation Rates in Pivotal Studies of Reslizumab in Patients With Severe Eosinophilic Asthma1923

    Trial Study Design Regimens Primary Efficacy Endpoint
    Castro et al. (2015) Two identical multicenter, randomized, double-blind, placebo-controlled trials in total of 995 patients
    • RES 3 mg/kg IV (n = 218)
    • Placebo (n = 215)
    Administered once every four weeks for 52 weeks for total of 13 infusions
    Frequency of CAEs

      Results:

    • ○ RES: 0.90*
    • ○ Placebo: 1.80
    • RES 3 mg/kg IV (n = 232)
    • Placebo (n = 232)
    Administered once every four weeks for 52 weeks for total of 13 infusions
    Frequency of CAEs

      Results:

    • ○ RES: 0.86*
    • ○ Placebo: 2.11
    Bjermer et al. (2016) Multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose trial in 315 patients
    • RES 0.3 mg/kg IV (n = 104)
    • RES 3 mg/kg IV (n = 106)
    • Placebo (n = 105)
    Administered once every four weeks for 16 weeks for total of four doses
    Improvement in prebrochodilator FEV1

      Results:

    • ○ RES 0.3 mg/kg: 242 mL*
    • ○ RES 3.0 mg/kg: 286 mL*
    • ○ Placebo: 126 mL
    Corren J et al. (2016) Multicenter, randomized, double-blind, placebo-controlled study in 422 patients
    • RES 3 mg/kg IV (n = 340)
    • Placebo (n = 82)
    Administered once every four weeks for 16 weeks for total of four doses
    Change in FEV1 from baseline to week 16

      Results:

    • ○ RES: 225 mL
    • ○ Placebo: 187 mL

    CAE = clinical asthma exacerbation; FEV1 = forced expiratory volume in one second; IV = intravenous; RES = reslizumab.

    *Statistically significant improvement with RES compared with placebo

    Author bio: 
    Dr. Lam is a Clinical Pharmacist specializing in ambulatory care at Morristown Medical Center in Morristown, New Jersey, and a Clinical Assistant Professor in the Department of Pharmacy Practice at Fairleigh Dickinson University School of Pharmacy in Florham Park, New Jersey. Dr. Shah is a Clinical Pharmacist specializing in internal medicine at Morristown Medical Center. Dr. Mansukhani is a Clinical Pharmacist specializing in transitions of care at Morristown Medical Center and a Clinical Associate Professor in the Department of Pharmacy Practice and Administration at the Ernest Mario School of Pharmacy at Rutgers, the State University of New Jersey, in Piscataway, New Jersey.

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