FDA Approves First Oral Psoriatic Arthritis Therapy
Celgene's apremilast (Otezla) was found to alleviate joint pain and inflammation during clinical trials.
Celgene’s apremilast (Otezla) was found to alleviate joint pain and inflammation during clinical trials.
The FDA granted approval on March 21, 2014, to the Celgene Corporation’s psoriatic arthritis (PsA) drug apremilast (Otezla), making it the first FDA-approved oral therapy available for the treatment of PsA.
Apremilast acts as a selective inhibitor of phosphodiesterase 4 (PDE4) to modulate inflammation. The treatment provided greater relief than placebo for the symptoms of PsA during 3 multi-center, randomized, double-blind, placebo-controlled Phase III trials.
"Relief of pain and inflammation and improving physical function are important treatment goals for patients with active psoriatic arthritis," said Curtis Rosebraugh, MD, MPH, director of the FDA Office of Drug Evaluation II, in an FDA press release. "Otezla provides a new treatment option for patients suffering from this disease.”
During the trials, researchers examined the effect of apremilast on a total of 1493 patients with active PsA. Of the patients in the trials, more than 75% had previously been treated with disease-modifying anti-rheumatic drugs only, while 22% had previously undergone treatment with biologics.
During the first trial, 38% of patients treated twice daily with 30 mg of apremilast achieved the American College of Rheumatology criteria for 20% improvement (ACR20) by week 16, compared with 19% of patients on placebo. Similar results were found in the subsequent trials, according to Celgene.
Patients who received apremilast experienced a reduction in tender and swollen joint counts at week 16 compared with those receiving placebo, in addition to improvements in disease-related physical functioning. Apremilast patients also experienced improvement in the PsA-specific disease manifestations dactylitis and enthesitis.
The following adverse reactions occurred in at least 2% of apremilast patients and occurred more frequently than they did in placebo patients: diarrhea, nausea, headache, upper respiratory tract infection, vomiting, nasopharyngitis, and upper abdominal pain. Of the patients taking apremilast, 4.6% discontinued treatment as a result of these reactions.
During clinical trials, 10% of patients taking apremilast and 3.3% of patients taking placebo reported weight loss of 5% to 10%. As a result, patients taking apremilast are advised to have their weight checked regularly by a health care professional.
An FDA press release advises that unexplained or clinically significant weight loss should be evaluated, with discontinuation of treatment considered. Apremilast treatment was also associated with increased reports of depression compared with placebo.
A registry of pregnant women taking apremilast must also be established to assess the risks related to exposure as a condition of FDA approval.
"[Apremilast] works differently from other therapies approved for psoriatic arthritis through the intracellular inhibition of PDE4," said Philip Mease, MD, director of the rheumatology clinical research division of Swedish Medical Center and a clinical professor at the University of Washington, in a Celgene press release. "The approval of an oral therapy with a novel mechanism of action for patients with psoriatic arthritis offers a different approach to patient care."