IMPORTANT SAFETY INFORMATION

Indications and clinical use:

  • OTEZLA (apremilast) is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
  • OTEZLA (apremilast), alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have had an inadequate response, intolerance, or contraindication to a prior disease-modifying anti-rheumatic drug (DMARD).
  • OTEZLA (apremilast) is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s disease who are candidates for systemic therapy.

OTEZLA has not been studied and is therefore not indicated in combination with other systemic (conventional or biologic) therapies or phototherapy for psoriasis. OTEZLA should be used with caution in patients ≥ 65 years of age.

Contraindications:

  • Pregnancy
  • Women who are breastfeeding

Relevant warnings and precautions:

  • History of tachyarrhythmia or conditions worsened by increases in heart rate
  • Weight loss (monitor regularly)
  • Diarrhea, nausea, and vomiting
  • Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose–galactose malabsorption
  • Severe immunological diseases, severe acute infectious diseases, or patients treated with immunosuppressive medicinal products; experience in patients with latent infections is limited
  • Not recommended in combination with potent immunosuppressants, including biological therapies and cyclosporine
  • Headache and migraine
  • History of depression and/or suicidal thoughts or behaviour
  • Severe renal impairment

For more information:

Please consult the Product Monograph at https://www.amgen.ca/-/media/Themes/CorporateAffairs/amgen-ca/amgen-ca/documents/products/en/otezla_pm.pdf for important information relating to adverse reactions, drug interactions, dosing instructions, and dosage adjustments in patients with severe renal impairment, which have not been discussed in this piece.

The Product Monograph is also available by calling us at 1-866-502-6436.

STUDY DESIGNS

ESTEEM 1 study (moderate-to-severe plaque psoriasis):1,3

A multicentre, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of OTEZLA for the treatment of moderate-to-severe plaque psoriasis.

Patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area [BSA] ≥ 10%, static Physician’s Global Assessment [sPGA] ≥ 3) were randomized 2:1 to OTEZLA 30 mg BID or placebo (N=844). At week 16, all placebo patients were switched to OTEZLA (placebo/OTEZLA) through week 32. From weeks 32–52, a selected subgroup of patients underwent a Randomized Treatment Withdrawal Phase.

The primary endpoint was the proportion of patients who achieved PASI-75 at week 16.

PALACE 1 study (active psoriatic arthritis):1,9

A multicentre, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of OTEZLA for the treatment of active psoriatic arthritis.

Patients with active psoriatic arthritis (swollen joints ≥ 3, tender joints ≥ 3), despite prior or current treatment with disease-modifying anti-rheumatic drug (DMARD) therapy, were randomized 1:1:1 to OTEZLA 20 mg BID (the current recommended dose is OTEZLA 30 mg BID), OTEZLA 30 mg BID, or placebo (N=504). Patients were allowed to receive stable doses of concomitant methotrexate (MTX) (≤ 25 mg/week), sulfasalazine (SSZ) (≤ 2 g/day), leflunomide (LEF) (≤ 20 mg/day), low-dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone/day), and/or nonsteroidal anti-inflammatory drugs (NSAIDs) during the trial. At week 16, non-responsive patients (whose tender and swollen joint counts had not improved by at least 20%) were re-randomized (1:1, blinded) to either OTEZLA 20 mg or 30 mg. At week 24, all remaining placebo patients were re-randomized (1:1, blinded) to either OTEZLA 20 mg or 30 mg through week 52.

The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 16.

RELIEF study (oral ulcers associated with Behçet’s disease):1

A multicentre, randomized, placebo-controlled trial enrolled a total of 207 adult patients with oral ulcers associated with Behçet’s disease.

Patients were previously treated with at least one nonbiologic Behçet’s disease medication and were candidates for systemic therapy. Patients met the International Study Group (ISG) Criteria for Behçet’s disease. Patients had at least 2 oral ulcers at screening and at least 2 oral ulcers at randomization and without currently active major organ involvement. Concomitant treatment for Behçet’s disease was not allowed. Patients were randomized 1:1 to receive either OTEZLA 30 mg twice daily or placebo for 12 weeks (placebo-controlled phase). After week 12, all patients received OTEZLA 30 mg twice daily from weeks 12–64 (open-label active-treatment phase). Efficacy was assessed based on the number and pain of oral ulcers.

The primary endpoint was the area under the curve (AUC) for the number of oral ulcers from baseline through week 12.

REFERENCES

  1. Amgen Canada Inc. OTEZLA® (apremilast) Product Monograph. August 5, 2020.
  2. Amgen Canada Inc. Data on file (NOV2022 MedReg Letter).
  3. Papp K, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37-49.
  4. Celgene Corp. Data on file (MAR2016 Patient Picture Project).
  5. Health Canada. OTEZLA Summary Basis of Decision (SBD) 2015. Available at: https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00238. Retrieved March, 2018.
  6. Celgene Corp. Data on file (Clinical Study Report CC-10004-PSOR-008).
  7. Amgen Canada Inc. Data on file (FEB2022 MedReg Letter).
  8. Kavanaugh A, et al. Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis. J Rheumatol. 2015;42(3):479-488.
  9. Kavanaugh A, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73(6):1020-1026.
  10. Amgen Canada Inc. Data on file (APR2021 MedReg Letter).
  11. Amgen Canada Inc. Data on file (AUG2020 MedReg Letter).
  12. Hatemi G, et al. Trial of apremilast for oral ulcers in Behçet's syndrome. N Engl J Med. 2019;381(20):1918-1928.