The FDA ( Food and Drug Administration ) has approved Otezla ( Apremilast ), a oral selective inhibitor of phosphodiesterase 4 ( PDE4 ), for the treatment of adult patients with active psoriatic arthritis. A chronic disorder, psoriatic arthritis is characterized by pain, stiffness, swelling and tenderness of the joints, inflammation of specific ligaments and tendons, and a decrease in physical functioning.
Otezla is the only FDA-approved oral treatment for psoriatic arthritis.
The approval was based on safety and efficacy results from three multi-center, randomized, double-blind, placebo-controlled trials - PALACE 1, 2 and 3 - conducted in adult patients with active psoriatic arthritis who were inadequately controlled by disease-modifying anti-rheumatic drugs ( DMARDs ) and/or biologics. More than 75% of patients were previously treated with DMARDs only and 22% of patients were previously treated with biologics.
Otezla treatment with or without (±) concomitant DMARDs, compared with placebo ± concomitant DMARDs, resulted in greater improvement in the signs and symptoms of psoriatic arthritis, as demonstrated by the proportion of patients with an ACR 20 response at week 16.
In PALACE-1, 38% of patients treated with Otezla ( Apremilast ) 30 mg twice daily achieved an ACR 20 response at week 16 versus 19% of patients on placebo.
Consistent results were observed in PALACE-2 and PALACE-3.
Improvement in ACR 50 and ACR 70 responses were observed at week 16 across the three studies.
A characteristic of psoriatic arthritis is tenderness and swelling in and around the joints. At week 16, patients treated with Otezla achieved a reduction in tender and swollen joint counts compared with placebo.
Otezla treatment resulted in improvement for each of the seven ACR components measured, compared with placebo, at week 16. Improvements were also seen in disease-related physical functioning.
Treatment with Otezla resulted in improvement in dactylitis ( inflammation of fingers and toes ) and enthesitis ( inflammation at sites where tendons or ligaments insert into bone ) in patients with these pre-existing symptoms. Enthesitis and dactylitis are specific disease manifestations related to psoriatic arthritis.
In clinical trials, the majority of the most common adverse reactions occurred within the first two weeks of treatment and tended to resolve over time with continued dosing. Adverse reactions reported in at least 2% of patients on Apremilast 30 mg twice daily and at least 1% greater than that observed in patients on placebo for up to 16 weeks were diarrhea, nausea, headache, upper respiratory tract infection, vomiting, nasopharyngitis, and upper abdominal pain.
The proportion of patients who discontinued treatment due to any adverse reaction was 4.6% for patients taking Otezla 30 mg twice daily and 1.2% for patients taking placebo.
The most common adverse reactions leading to discontinuation among patients treated up to 16 weeks with Otezla 30 mg twice daily were nausea ( 1.8% ), diarrhea ( 1.8% ) and headache ( 1.2% ).
Otezla is contraindicated for use in patients with a known severe allergic reaction to Apremilast or other components in Otezla. Across the three PALACE studies, 1.0% ( 10/998 ) of patients treated with Otezla reported depression or depressed mood compared with 0.8% ( 4/495 ) treated with placebo; 0.3% ( 4/1441 ) of patients treated with Otezla discontinued treatment due to depression or depressed mood compared with none among placebo-treated patients.
In the PALACE studies, 10% of patients taking Otezla, compared with 3.3% of patients taking placebo, reported weight loss of five to ten percent. It is recommended that patients taking Otezla have their weight checked regularly.
During the placebo-controlled phase of the clinical trials, the rate of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, was comparable between placebo and Otezla groups.
The product labeling does not require routine laboratory monitoring for patients taking Otezla.
PALACE 1, 2 and 3 are the pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. Across these studies, approximately 1,500 patients were randomized 1:1:1 to receive either Apremilast 20 mg twice daily, Apremilast 30 mg twice daily, or identically-appearing placebo, for 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two Apremilast groups, while others remained on placebo through week 24. After week 24, patients began a subsequent long term, open-label, active treatment phase.
The PALACE 1, 2 and 3 studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with oral DMARDs, and/or biologics, with some patients who had previously failed a tumor necrosis factor ( TNF ) blocker.
The primary endpoint of the PALACE 1, 2 and 3 studies was the modified American College of Rheumatology ( ACR ) criteria for 20 percent improvement ( ACR20 ) at week 16. Secondary endpoints included other measures of signs and symptoms of psoriatic arthritis, physical functioning, and patient-reported outcomes. ( Xagena )
Source: Celgene, 2014