otezla ® - apremilast manufacturer: celgene corporation fda approval date: 9/23/14

Otezla® - apremilast

Manufacturer: Celgene Corporation

FDA Approval Date: 9/23/14

Otezla®- apremilast

Clinical Application

• Indications:• Treatment of moderate to severe plaque

psoriasis in patients who are candidates for phototherapy or systemic therapy

• Treatment of active psoriatic arthritis in adults

• Place in therapy:• Oral alternative to Methotrexate and

retinoids


Clinical Application• Contraindications:

• Hypersensitivity to apremilast or any component of the formulation

• Warnings: • Depression, suicidal ideation, and mood changes

have been reported

• May cause weight loss

• Precautions:• Systemic exposure increased in patients with CrCl

<30 ml/min


Clinical Application

• Pregnancy:• Category C

• Lactation:• Excretion in breast milk is unknown, use

caution


Drug Facts

• Pharmacology:

Inhibits phosphodiesterase-4 (PDE4) preventing it from degrading cyclic adenosine monophosphate (cAMP) to AMP resulting in increased cAMP levels intracellularly. Cyclic AMP down regulates inflammatory response through several inflammatory mediators.


Drug Facts

• Pharmacokinetics:

A Well absorbed; ~73% bioavailability

D Vd 87 L; 68% protein bound

M Hepatic: Major CYP3A4 Minor CYP1A2 and CYP2A6

E t1/2 6-9h; 58% in urine, 39% in feces


Drug Interactions

• Drug Interactions – Object Drugs: • None


Drug Interactions

• Drug Interactions – Precipitant Drugs: • Bosentan: ↓ concentration

• Strong CYP3A4 inducers: ↓concentration

• Dabrafenib: ↓ concentration

• Deferasirox: ↓ concentration

• Siltuximab: ↓ concentration

• St. John’s Wort: ↓ concentration

• Tocilizumab: ↓ concentration


Adverse Effects

• Common Adverse Effects:

• Serious Adverse Effects:

Diarrhea (9%) [2%] Nausea (9%) [3%]

Headache (6%) [2%] URI (4%) [2%]

Nasopharyngitis (3%) [2%] Vomiting (3%) [0.4%]

Abdominal pain (2%) [0.2%]

Weight Loss (10-12%) [3-5%]

Depression (1%) [0.8-1.3%]


Monitoring Parameters

• Efficacy Monitoring:• Signs and Symptoms of

Psoriasis/psoriatic arthritis within 3 months of initiation

• Toxicity Monitoring:• SCr: 3 months and annually

• Weight Loss: 3 months

• Depression: 3 months


Prescription Information

• Dosing: 30 mg BID• Titration:

• Cost: UpToDate.com Accessed 11/03/2014

• Starter Pack: $1012

• 30 mg Tablets #60: $2250

Day 1

Day 2 Day 3 Day 4 Day 5 Day 6

AM AM PM AM PM AM PM AM PM AM PM

10 mg

10 mg

10 mg

10 mg

20 mg

20 mg

20 mg

20 mg

30 mg

30 mg

30 mg


Literature Review

• Phase 3 Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) Trial

• Randomized, placebo controlled study

• Included 504 patients from 13 countries

Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020-26


Literature Review• Phase 1: 24 weeks

• 1:1:1 randomization to receive either apremilast 30 mg BID, apremilast 20 mg BID, or placebo

• Phase 2: 28 weeks • Patients who received placebo in Phase 1 were

randomized 1:1 to receive apremilast 20 mg BID or apremilast 30 mg BID

• Patients receiving apremilast in Phase 1 remained on that dose



Literature Review

• Primary Endpoint: Proportion of patients with 20% improvement in modified ACR response criteria at week 16

• Secondary Endpoints: • Change from baseline in Health Assessment

Questionnaire- Disability Index (HAQ-DI) at week 16

• Improvement in S/Sx of PsA, physical function, and psoriasis at 24 weeks



Literature Review

• Baseline Characteristics


Parameter PlaceboApremilast 20 mg BID

Apremilast 30 mg BID

Age (years) 51.1 48.7 51.4

BMI 31.1 30.9 30.6Mean duration of PsA (years) 7.3 7.2 8.1

Mean HAQ-DI (0-3) 1.2 1.2 1.2

Psoriasis involvement of BSA 3% or more (n) 68 77 82

Mean PASI Score (0-72) 9.1 7.4 9.2


Literature Review



Summary

• Apremilast is an effective oral agent for the treatment of psoriasis and psoriatic arthritis

• Maintenance Dose: 30 mg BID with dosing adjustment for CrCl <30 ml/min

• Weight and signs of depression must be monitored for as these are potentially serious adverse effects


References

1. http://www.otezla.com

2. Otezla (apremilast) package insert. Celgene Corporation. Sept. 2014.

3. Apremilast. Lexicomp Drug Information. Accessed through UpToDate. Accessed on Nov 3, 2014.

4. Kavanaugh A, et al. Ann Rheum Dis 2014;73:1020-1026

5. Papp KA, et al. JEADV 2013,27, e376-383

otezla ® - apremilast manufacturer: celgene corporation fda approval date: 9/23/14

Documents

concentration slide

caution slide

crcl slide

bid patients

concentration dabrafenib

concentration siltuximab

concentration deferasirox

concentration tocilizumab