Otezla (apremilast) - 3 indications

Scroll down for information on each indication:

• for the treatment of psoriatic arthritis; approved March 2014
• for the treatment of moderate to severe plaque psoriasis; approved September 2014 - expanded December of 2021 to include patients with plaque psoriasis across al severities who are candidates for phototherapy or systemic therapy
• for the treatment of oral ulcers associated with Behçet’s Disease; approved July 2019

General Information

Otezla (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP).

Otezla is specifically indicated for the following:

• adults with active psoriatic arthritis
• adults with all severities of plaque psoriasis who are candidates for phototherapy or systemic therapy
• adults with oral ulcers associated with Behçet’s Disease

Otezla is supplied as a tablet for oral administration. The recommended dosing for all indications is as follows: Otezla should be titrated from Day 1 to Day 5. Following the 5-day titration, the recommended maintenance dosage is 30 mg twice daily taken orally starting on Day 6. This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.

Day 1: AM: 10mg

Day 2: AM: 10mg and PM: 10mg

Day 3: AM: 10mg and PM: 20mg

Day 4: AM; 20mg and PM: 20mg

Day 5: AM; 20mg and PM: 30mg

Day 6 and thereafter: AM; 30mg and PM: 30mg

Mechanism of Action

Otezla (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. The specific mechanism(s) by which apremilast exerts its therapeutic action is not well defined.

Side Effects

Adverse effects associated with the use of Otezla for psoriatic arthritis may include, but are not limited to, the following:

• diarrhea
• nausea
• headache

Adverse effects associated with the use of Otezla for psoriasis may include, but are not limited to, the following:

• diarrhea
• nausea
• upper respiratory tract infection
• headache, including tension headache

Adverse effects associated with the use of Otezla for Behçet’s Disease may include, but are not limited to, the following: 

• diarrhea
• nausea
• headache
• upper respiratory tract infection

Indication 1 - psoriatic arthritis

approved March 2014

Clinical Trial Results

The FDA approval of Otezla was based on three multi-center, randomized, double-blind, placebo-controlled trials (Studies PsA-1, PsA-2, and PsA-3) of similar design. A total of 1,493 adult patients with active PsA (= 3 swollen joints and = 3 tender joints) despite prior or current treatment with disease-modifying antirheumatic drug (DMARD) therapy were randomized. Patients enrolled in these studies had a diagnosis of PsA for at least 6 months. Across the three studies, patients were randomly assigned to placebo , Otezla 20 mg or 30 mg, given orally twice daily. Titration was used over the first 5 days. Patients were allowed to receive stable doses of concomitant medication. The primary endpoint was the percentage of patients achieving American College of Rheumatology (ACR) 20 response at Week 16. Otezla (30 mg twice daily) ± DMARDs, compared with placebo ± DMARDs resulted in a greater improvement in signs and symptoms of psoriatic arthritis as demonstrated by the proportion of patients with an ACR 20 response at Week 16. PsA-1: placebo group = 19% versus Otezla = 38%; PsA-2: placebo group = 19% versus Otezla = 32%; PsA-3: placebo group = 18% versus Otezla = 41%.

Indication 2 -  plaque psoriasis of all severities

approved September 2014

Clinical Trial Results

The FDA approval of Otezla for psoriasis was based on two multicenter, randomized, double-blind, placebo-controlled trials (Studies PSOR-1 and PSOR-2) which enrolled a total of 1,257 subjects 18 years of age and older with moderate to severe plaque psoriasis. Study PSOR-1 enrolled 844 subjects and Study PSOR-2 enrolled 413 subjects. In both studies, subjects were randomized 2:1 to Otezla 30 mg BID or placebo for 16 weeks. Both studies assessed the proportion of subjects who achieved PASI-75 at Week 16 and the proportion of subjects who achieved a sPGA score of clear (0) or almost clear (1) at Week 16. PSOR-1: PASI-75 placebo: 15 (5.3%) and Otezla: 186 (33.1%). sPGA score placebo 11 (3.9%) and Otezla 122 (21.7%). PSOR-2: PASI-75 placebo: 8 (5.8%) and Otezla 79 (28.8%). sPGA score placebo 6 (4.4%) and Otezla 56 (20.4%).

Indication 3 - oral ulcers associated with Behçet’s Disease

approved July 2019

Clinical Trial Results

The FDA approval of Otezla for oral ulcers associated with Behçet’s Disease was based on the randomized, placebo-controlled, double-blind Phase 3 RELIEF study evaluating Otezla in 207 adult patients with Behçet’s Disease with active oral ulcers who were previously treated with at least one nonbiologic medication and were candidates for systemic therapy. Results showed Otezla 30 mg BID resulted in a 42.7 point reduction from baseline in the pain of oral ulcers as measured by the visual analog scale (VAS) at week 12, compared with an 18.7 point reduction with placebo. The proportion of patients achieving an oral ulcer complete response (oral ulcer-free) at week 12 was 52.9% in the Otezla arm and 22.3% in the placebo arm. The proportion of patients achieving oral ulcer complete response by week 6 and who remained oral ulcer-free for at least six additional weeks during the 12-week treatment phase was 29.8% in the Otezla arm and 4.9% in the placebo arm. The daily average number of oral ulcers during the 12-week treatment phase was 1.5 in the Otezla arm and 2.6 in the placebo arm (based on oral ulcer counts measured at baseline and at weeks 1, 2, 4, 6, 8, 10 and 12).