By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical 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 second monoclonal antibody targeting the interleukin-5 receptor has been approved for the maintenance treatment of severe asthma. Reslizumab follows mepolizumab (Nucala) and is marketed as Cinqair.

INDICATIONS

Reslizumab is indicated for add-on maintenance treatment of adult patients with severe asthma with eosinophilic phenotype.1

DOSAGE

The recommended dose is 3 mg/kg once every four weeks by IV infusion over 20-50 minutes.1 Reslizumab is available as 100 mg single-use 10 mL vials.

POTENTIAL ADVANTAGES

Reslizumab provides another option for the management of severe eosinophilic asthma.

POTENTIAL DISADVANTAGES

Reslizumab requires IV infusion, while mepolizumab is administered subcutaneously. The most common adverse event is the elevation of creatine phosphokinase (14% vs. 9% for placebo).1 Anaphylaxis occurred in 0.3% of patients receiving the drug. Anti-reslizumab antibodies develop in 5.4% of subjects during treatment.

COMMENTS

Reslizumab is a humanized monoclonal antibody (IgG4, kappa) produced by recombinant DNA technology in murine myeloma cells. It is an interleukin-5 antagonist. The efficacy of reslizumab was evaluated in four randomized, double-blind, placebo-controlled studies. Two were 52-week studies (n = 953) and two were 16-week studies (n = 811).1-5 Asthmatic subjects with an eosinophilic phenotype in the 52-week studies experienced at least one exacerbation requiring systemic corticosteroid use during the past 12 months and a blood eosinophil count of at least 400/mcL. Eighty-two percent received a medium-high dose inhaled steroid plus a long-acting beta agonist at baseline. Subjects were randomized to reslizumab 3 mg/kg every four weeks or 13 placebo doses. The primary endpoint was the frequency of asthma exacerbations, defined as a worsening of asthma that required use of 1) a systemic corticosteroid, 2) ≥ two-fold increase in the use of inhaled steroid for three or more days, or 3) an unscheduled visit to a healthcare provider (urgent treatment, ED visit, or hospital admission). Medical intervention was corroborated by decline in pulmonary function or worsening of clinical signs or symptoms. The annual rates of exacerbations in those treated with reslizumab declined 50-59% and those requiring hospitalization or ED visits by about one-third. A significantly higher proportion of the reslizumab group did not have an exacerbation by week 52 (62% and 75%) compared to 46-55% in the placebo group. Lung function (change in FEV1) was evaluated in all four studies and was the primary endpoint in the two 16-week studies. The second 16-week study did not require a minimum blood eosinophil count. This study evaluated the relationship between treatment effect and blood eosinophil counts. Change in FEV1 ranged from 93 mL to 160 mL for the first three studies and 76 mL for the fourth study. Researchers found no association between baseline eosinophil counts and treatment. Responses (≥ 0.5-point improvement) to the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaires were all numerically higher for reslizumab for the three studies. The difference between reslizumab and placebo was modest, as there was statistical difference for both questionnaires for one study and only one for the third study.2 A small study (n = 106) suggested patients with higher ACQ scores and nasal polyposis may show greater benefit.6

CLINICAL IMPLICATIONS

Eosinophilic asthma is a phenotype of asthma characterized by high eosinophil count in the blood, lung, and sputum. It is postulated that interleukin-5 is the key mediator of eosinophilic asthma.7 Reslizumab is the second monoclonal antibody interleukin-5 antagonist after mepolizumab. Currently, there are no direct comparisons between these two drugs. Both have been reported to reduce exacerbations about 50%; however, mepolizumab reduces oral corticosteroid use, but reslizumab appeared to show a numerically better improvement in lung function in clinical trials when compared across studies.1,8 The cost for mepolizumab 100 mg is $2,500. Reslizumab dose is weight-based at 3 mg/kg, requiring two vials for a 66 kg patient ($1,670) and three vials for patients 67 kg-100 kg ($2,505).

REFERENCES

  1. Cinqair Prescribing Information. Teva Pharmaceuticals. March 2016.
  2. FDA. Center for Drug Evaluation and Research, Application Number 761033Orig1s000, Summary Review. Available at: http://1.usa.gov/1sgzcOU. Accessed May 10, 2016.
  3. Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: Results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015;3:355-366.
  4. Bjermer L, Lemiere C, Maspero J, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: A randomized phase 3 study. Chest 2016 Apr 4. pii: S0012-3692(16)47551-3. doi: 10.1016/j.chest.2016.03.032. [Epub ahead of print].
  5. Corren J, Weinstein S, Janka L, et al. Phase 3 study of reslizumab in patients with poorly controlled asthma: Effects across a broad range of eosinophil counts. Chest 2016 Mar 24. pii: S0012-3692(16)45715-6. doi: 10.1016/j.chest.2016.03.018. [Epub ahead of print].
  6. Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: A randomized, placebo-controlled study. Am J Respir Crit Care Med 2011;184:1125-1132.
  7. Varricchi G, Bagnasco D, Borriello F, et al. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: Evidence and unmet needs. Curr Opin Allergy Clin Immunol 2016;16:186-200.
  8. Nucala Prescribing Information. GlaxoSmithKline. November 2015.