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Clinical Rx Forum Volume 5 Issue 2

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Clinical Rx Forum Volume 5 Issue 2 In This Issue Ustekinumab for Crohn’s Disease ® ®®® Reslizumab for Eosinophilic Phenotype, From the Department of Pharmacy Severe Asthma March/April Issue 2017 Volume 5, Issue 2 Formulary Update FDA Medication Safety Alert: Risk of VTE with Test Ustekinumab for Crohn’s Disease osterone By: Christine Hwang, Pharm.D. Marcia J. Wyman, Pharm.D., BCPS Background: Crohn’s disease (CD) is shared p40 protein subunit on interleu- Drug Information Pharmacist a chronic inLlammatory disease of the kin-12 (IL-12) and interleukin-23 (IL- Editor 1,3 gastrointestinal (GI) system and can 23). It blocks the actions of IL-12/23 Mandy C. Leonard, Pharm.D., BCPS cause a wide spectrum of GI-related cytokines including natural killer cell System Director, Drug Use Policy and symptoms and complications. 1,2 The activation and CD4+ T-cell differentia- Formulary Management main goals of treatment are to suppress tion and activation, which contribute to Editor inLlammatory processes and induce the chronic inLlammation of CD. Usteki- Meghan K. Lehmann, Pharm.D., BCPS remission. Medical management for numab was Lirst approved by the Food Coordinator, Drug Information Services moderate-to-severe CD usually involves and Drug Administration (FDA) in 2009 Drug Information Specialist treatment with tumor necrosis factor to treat adult patients with moderate- Editor (TNF) blockers (e.g., inLliximab) and to-severe plaque psoriasis or psoriatic Marigel Constantiner, MSc, BCPS, CGP, CPh anti-integrin agents (e.g., vedolizumab). arthritis. In 2016, it gained FDA ap- Drug Information Specialist However, up to 40% of patients do not proval for moderately to severely active Associate Editor respond to TNF blockers; of those CD in adult patients who failed or were who fail TNF therapy, 47% do not re- intolerant to treatment with cortico- Christopher Snyder, B.S., R.Ph. 1,2 Drug Information Pharmacist spond to velodizumab. The high rate steroids or immunomodulators, but Associate Editor of non-response to the biologic thera- never failed a TNF blocker, or those pies warrants the need to evaluate who failed or were intolerant to one or Kara J. Sink, B.S., R.Ph. newer agents. more TNF blockers. Drug Information Pharmacist Associate Editor A Novel Indication: Ustekinumab, Key Clinical Trial: Ustekinumab’s ® Brian Hoffmaster, Pharm.D., BCPS known by the brand name Stelara FDA approval for CD was based on Student Education Pharmacist (Janssen Biotech, Inc.), is a human im- three phase 3 randomized, placebo- Associate Editor munoglobulin G1K monoclonal anti- controlled studies. 4 Two of the studies, body with high binding capacity to UNITI-1 and UNITI-2, investigated the Maya Wai, Pharm.D. Drug Information Pharmacist Associate Editor Reslizumab for Eosinophilic Phenotype, Severe Asthma Scott Knoer, MS, Pharm.D., FASHP By: Jacyln Hawn, Pharm.D. Chief Pharmacy OfPicer Background: Eosinophilic asthma is that received Food and Drug Admin- characterized by high eosinophil levels istration (FDA) approval on March 23, in the blood and bronchial Lluid, which 2016 for add-on maintenance treat- can lead to severe asthma that is poorly ment for patients with an eosinophilic controlled by inhaled corticosteroids phenotype, severe asthma who are From the Department of Pharmacy and bronchodilators. 1 This asthma phe- 18 years and older. 4 Drug Information Service notype is most prevalent in adults and is estimated to be present in less than Mechanism of Action: Reslizumab is (216) 444-6456, option #1 5% of cases with adult–onset asthma. 2, 3 an interleukin-5 (IL-5) antagonist. 4 In- Elevated eosinophil levels in the serum terleukin-5 is the key cytokine respon- Comprehensive information about and sputum are independent risk fac- sible for the growth and differentiation, medications, biologics, nutrients, tors for future exacerbations. 1 Res- recruitment, activation, and survival of and drug therapy lizumab (Cinqair ®; Teva Respriatory) is eosinophils. Eosinophils are one of the an anti-asthmatic monoclonal antibody (Continued on page 3) use of intravenous (IV) ustekinumab for induction For the induction dose, the contents of the therapy in either patients who had primary or second- single-dose vials should be diluted in 250 mL of ary non-response or intolerable side effects to TNF 0.9% sodium chloride and infused intravenously blockers (UNITI-1) or conventional therapy with im- through a 0.2 micrometer Lilter over at least 1 hour. munomodulators (UNITI-2). Patients were random- For the maintenance dose, the 90 mg preLilled syringe ized to receive either 130 mg or ~6 mg/kg of IV usteki- is administered subcutaneously 8 weeks after the numab or placebo. The primary endpoint for these induction dose and then every 8 weeks thereafter. induction studies was a clinical response at week 6, The single-dose vial and preLilled syringe must be which was deLined as at least a 100 point decrease stored at refrigerated temperatures (2° to 8°C [36° to from baseline in the Crohn’s Disease Activity Index 46°F]). The diluted IV infusion can be stored at room (CDAI) score. In both studies, a signiLicantly higher temperature (up to 25°C [77°F]) for up to 4 hours. percentage of patients who received IV ustekinumab experienced a clinical response compared to placebo Formulary Status : Intravenous ustekinumab was (P=0.002 [130 mg vs. placebo] and P=0.003 [6 mg/kg recently added to the CCHS Adult Formulary restricted vs. placebo] in UNITI-1; P<0.001 for both comparisons to the Department of Gastroenterology for outpatient in UNITI-2). Patients who completed the induction use only. The intravenous formulation of ustekinumab trials were enrolled in the 44-week IM-UNITI was also added to the CCHS Pediatric Formulary re- maintenance trial, which randomized patients to stricted to the Department of Pediatric Gastroenterolo- receive 90 mg subcutaneous ustekinumab either every gy for outpatient use only for patients ≥ 18 years old 8 weeks or every 12 weeks or placebo. The primary with moderate to severe Crohn’s disease that have endpoint was clinical remission at week 44, which oc- failed therapy with at least one TNF blocker. The sub- curred in a signiLicantly higher percentage of patients cutaneous syringe formulation was not added to either who received ustekinumab for maintenance compared formulary, since patients can self-administer mainte- to placebo (P=0.005 [every 8 weeks vs. placebo] and nance doses at home. P=0.04 [every 12 weeks vs. placebo]). This study also References: showed that every 8 week administration of the 1. Hansen T, Targownik LE. Ustekinumab for the treatment of Crohn’s maintenance dose was more effective in maintaining disease. Expert Rev Gastroenterol Hepatol. 2016;10ʚ9ʛ:989-94. remission compared to every 12 weeks. The most 2. Harris KA, Horst S, Gadani A, Nohl A, Annis K, Duley C, et al. Patients with refractory Crohn's disease successfully treated with usteki- common side effects were CD events, arthralgia, pyrex- numab. InLlamm Bowel Dis. 2016;22ʚ2ʛ:397-401. ia, headache, and nasopharyngitis. From these results, 3. Stelara® ʞpackage insertʟ. Horsham, PA: Janssen Biotech, Inc.; Septem- the authors concluded that ustekinumab administered ber 2016. 4. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR. initially as an IV infusion followed every 8 weeks by Ustekinumab as induction and maintenance therapy for Crohn's dis- subcutaneous therapy induces response and remission ease. N Engl J Med. 2016;375ʚ20ʛ:1946-60. 5. AmeriSourceBergen.com ʞInternetʟ Chesterbrook: AmerisourceBergen in patients with moderate-to-severe CD that is refrac- Drug Corporation: 2016. Available from: http:// tory to either TNF blockers or conventional therapy. passport.amerisourcebergen.com/irj/ortal Accessed: December 2016. Availability and Cost: The IV formulation of ustekinumab is available as a 130 mg/26 mL single- dose glass vial and has a suggested wholesale price (SWP) of $1920 per vial. 5 The subcutaneous formula- tion is available as a 90 mg/mL preservative-free, pre- Lilled single-dose syringe and has a SWP of $21,216 per syringe. The glass vial for the IV formulation is latex- free, but the preLilled syringe contains latex. Dosing and Administration: The IV induction dose of ustekinumab is weight-based, but utilizes entire vials (no need to dose round) and is as follows:3 • 260 mg (2 vials) for patients weighing ≤ 55 kg • 390 mg (3 vials) for patients weighing >55 to 85 kg • 520 mg (4 vials) for patients weighing > 85 kg 2 (Continued from page 1) many types of mediators involved in the inLlammatory dose of reslizumab is 3 mg/kg which is mixed process. 4,5 Reslizumab reduces the production and sur- in 50 mL of 0.9% sodium chloride and infused over vival of eosinophils by antagonizing the IL-5 pathway 20 to 50 minutes every 4 weeks. There is no dosage and therefore, reduces inLlammation associated with adjustment for reduced renal or hepatic function. asthma. The exact mechanism of action of reslizumab There have been no studies to determine compatibility in asthma has not been deLinitively established. 4 with other IV drugs, and thus, reslizumab should be administered separately. After receiving a dose of res- EfLicacy: Three hundred and Lifteen patients with lizumab, patients should be monitored by a healthcare inadequately controlled eosinophilic phenotype, se- professional for an appropriate period of time for signs vere asthma were included in a randomized, double- and symptoms of anaphylaxis. blind, placebo-controlled trial. 6 The primary outcome was to compare the change in Forced Expiratory Vol- Role in Therapy: Reslizumab is indicated as add-on ume (FEV 1) from baseline to 16 weeks among treat- maintenance treatment for patients with an eosino- ment groups, reslizumab 0.3 mg/kg (n=104), res- philic phenotype, severe asthma who are 18 years and lizumab 3 mg/kg (n=106), or placebo (n=105).
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