Apremilast Improves Joint and Skin Involvement in Psoriatic Arthritis

Apremilast, an oral phosphodiesterase 4 inhibitor, may represent a new oral treatment option for patients with psoriatic arthritis (PsA) and current skin involvement, according to a new study. The drug, which has a unique mode of action, was effective for both the articular and cutaneous manifestations of the disease.

“We can we get prolonged responses with apremilast. On balance, it is a very safe drug and has great patient acceptance since patients take it by mouth twice a day. We don’t have to monitor safety parameters as much as with a biologic. For some people, it’s a very effective drug,” said Charles Birbara, M.D., of the University of Massachusetts Medical School.

Apremilast modulates the inflammatory response by upregulating anti-inflammatory cytokines while downregulating pro-inflammatory factors. The drug showed clinical benefits in an earlier study called PALACE 1.

Dr. Birbara is a co-author of a follow-up phase III, randomized, controlled trial (PALACE 3). That trial included 505 patients who were randomized to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily. Rescue therapy with apremilast was designated at week 16 for placebo patients who did not achieve 20% improvement in swollen and tender joint counts. At week 24, the remaining placebo patients were then randomized to apremilast 20 mg twice daily or 30 mg twice daily. The efficacy and safety of apremilast were assessed over 52 weeks.

The trial included patients who had at least three swollen and three tender joints and had active skin disease with at least one lesion larger than 2 cm. All of the patients had had previous treatment with a conventional disease-modifying antirheumatic drug (DMARD), but no more than 10% could have previously failed on a tumor necrosis factor (TNF) inhibitor.

Patients who were on methotrexate, leflunomide or sulfasalazine were allowed to continue at stable doses; steroids and nonsteroidal anti-inflammatory drugs were also permitted.

At week 16, significantly more patients receiving apremilast 20 mg twice daily (28%) and 30 mg twice daily (41%) achieved 20% improvement in American College of Rheumatology response criteria versus placebo (18%). The mean decrease in the Health Assessment Questionnaire-Disability Index score was significantly greater with apremilast 30 mg twice daily (−0.20) versus placebo (−0.07).

Also at week 16, in patients with baseline psoriasis body surface area involvement ≥3%, significantly more apremilast 30 mg twice daily patients achieved 50% reduction from baseline Psoriasis Area and Severity Index score (41%) versus placebo (24%). At week 52, observed improvements in these measures demonstrated sustained response with continued apremilast treatment.

Significant differences were seen on several other efficacy measures for the apremilast 30-mg dose versus placebo, including mean change in swollen joint count, patient's global assessment, physician's global assessment and disease activity score.

Most adverse events were mild to moderate in severity, Dr. Birbara said. The most common were diarrhea, nausea, headache and upper respiratory tract infection.

“Apremilast 30 mg twice daily is a fairly effective drug, as effective, if not more so, than other so-called DMARDs, such as methotrexate, in PsA,” he said adding that TNF inhibitors or biologic medications are more predictable than apremilast as oral drugs.  [[{"type":"media","view_mode":"media_crop","fid":"51156","attributes":{"alt":"©DavidSmart/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_8975668514694","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6298","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©DavidSmart/Shutterstock.com","typeof":"foaf:Image"}}]]

“Some PsA patients may do better with apremilast than methotrexate. A patient with extensive plaque psoriasis covering 15-20% of body, I would be inclined to use a TNF inhibitor, which is usually more effective in combination with methotrexate. A patient who has less involvement may do well with apremilast. The results show that apremilast 30 mg twice daily for patients with up to 3% involvement did quite well. If a patient can tolerate the drug twice daily, there is no question it has significant efficacy across a broad range of patients with PsA,” Dr. Birbara said.

He said that most psoriatic patients have some development of psoriasis, and for some patients, psoriatic arthritis precedes the development of psoriasis. “A patient with classic asymmetrical swelling of joints who has a family history of psoriasis or Crohn’s disease may havepsoriatic arthritis. In that case, I could use apremilast, but methotrexate may be the drug of first choice. However, some patients who go on methotrexate have a limited ability to afford biologic therapy. If I add apremilast to methotrexate, I can get great results in treating psoriatic arthritis.  

“I saw a patient today I know has PsA,” Dr. Birbara continues. “He is an older man with two children who have psoriasis. He has chronic joint disease symptoms that are asymmetrical. For him, I might consider initiating therapy with apremilast.”

Dr. Birbara believes that apremilast has “clearly demonstrated a niche in the treatment of psoriasis and PsA.  It is a good option, both efficacious and proven.”

He notes that rheumatologists treating psoriatic arthritis now have a range of therapies, including apremilast, to modify the course of the disease. Other new therapies, such as anti-IL-17 and anti-IL-23 agents, are in development. “In the near future, the broad number of options for PsA will be like those now available for rheumatoid arthritis treatment,” Dr. Birbara said.

References:

Peter Schafer. “Apremilast mechanism of action and application to psoriasis and psoriatic arthritis,”Biochemical Pharmacology. June 15, 2012.  http://dx.doi.org/10.1016/j.bcp.2012.01.001

Kavanaugh A1, Mease PJ, et al. “Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor,” Annals of the Rheumatic Diseases.  March 4, 2014; 73:1020-1026 doi:10.1136/annrheumdis-2013-205056

Edwards CJ, Blanco FJ, et al. “Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3),”Annals of the Rheumatic Diseases. Jan. 20, 2016.  DOI: 10.1136/annrheumdis-2015-207963.