FDA Approves Otezla (Apremilast) to Treat Psoriatic Arthritis
Drug is only approved oral therapy for PsA
The FDA has given the nod to Otezla (apremilast, Celgene Corp.) for the treatment of adults with active psoriatic arthritis (PsA).
PsA is a form of arthritis that affects some people with psoriasis. Most people develop psoriasis first and are later diagnosed with PsA. Joint pain, stiffness, and swelling are the main signs and symptoms of PsA.
Currently approved treatments for PsA include corticosteroids, tumor necrosis factor (TNF) blockers, and an interleukin (IL)-12/IL-23 inhibitor. Otezla (apremilast) is the only FDA-approved oral treatment for PsA.
The agency’s approval was based on safety and efficacy results from three randomized, double-blind, placebo-controlled trials — PALACE 1, 2, and 3 — conducted in adults with active PsA who were inadequately controlled by disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics. More than 75% of the patients were previously treated with DMARDs only, and 22% of the patients were treated with biologics.
Treatment with apremilast (with or without concomitant DMARDs) compared with placebo (with or without concomitant DMARDs) resulted in greater improvement in the signs and symptoms of PsA, as demonstrated by the proportion of patients with a 20% improvement in American College of Rheumatology criteria (ACR 20) at week 16. In the PALACE-1 trial, 38% of patients treated with apremilast 30 mg twice daily achieved ACR20 at week 16 compared with 19% of the patients given placebo. Similar results were achieved in the PALACE-2 and PALACE-3 trials. Improvement in ACR50 and ACR70 responses were observed at week 16 across the three studies.
A characteristic of PsA is tenderness and swelling in and around the joints. At week 16, patients treated with apremilast achieved a reduction in tender and swollen joint counts compared with patients given placebo. Treatment with apremilast 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 apremilast 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 the phase III clinical trials, adverse reactions (AEs) reported in at least 2% of patients treated with apremilast 30 mg twice daily and at least 1% greater than that observed in patients given placebo for up to 16 weeks were diarrhea, nausea, headache, upper respiratory tract infections, vomiting, nasopharyngitis, and upper abdominal pain. The proportions of patients who discontinued treatment because of an AE was 4.6% for patients taking apremilast 30 mg twice daily and 1.2% for patients taking placebo. The most common AEs leading to discontinuation among patients treated for up to 16 weeks with apremilast 30 mg twice daily were nausea (1.8%), diarrhea (1.8%), and headache (1.2%).
Otezla (apremilast) is contraindicated for use in patients with a known severe allergic reaction to apremilast or to other components of Otezla. In the PALACE studies, 10% of patients treated with apremilast reported weight loss of 5% to 10%. It is recommended that patients taking apremilast have their weight checked regularly.
Treatment with apremilast was also associated with an increase in reports of depression compared with placebo.
During the placebo-controlled phase of the phase III trials, the rates of major adverse cardiac events, serious infections (including opportunistic infections), and malignancies were comparable between the apremilast and placebo groups. The product labeling does not require routine laboratory monitoring for patients taking Otezla.
The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risks to pregnant women related to exposure to apremilast.