Pam Harrison

June 24, 2015

ROME — Apremilast (Otezla, Celgene), a new oral option for the treatment of psoriatic arthritis, shows sustained and clinically meaningful improvement in key symptoms of the disease out to 104 weeks, a pooled analysis indicates.

"Enthesitis and dactylitis are known to be distinguishing features of psoriatic arthritis, and they can be difficult to treat," said Dafna Gladman, MD, from the Toronto Western Research Institute.

"Apremilast induces significant improvement in both enthesitis and dactylitis through to week 104, with about 50% of patients achieving a Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] of zero and about 75% achieving a dactylitis count of zero, she reported. In addition, "no new safety concerns emerged during 104 weeks of exposure."

Pooled efficacy and safety results from three trials — PALACE 1, PALACE 2, and PALACE 3 — were presented here at the European League Against Rheumatism Congress 2015.

The PALACE trials compared apremilast, an oral phosphodiesterase 4 inhibitor, with placebo in patients with active psoriatic arthritis despite previous treatment with conventional or biologic disease-modifying antirheumatic drugs (DMARDs). Throughout the study, patients could remain on methotrexate, another DMARD, or a combination of DMARDs.

Patients were randomized to apremilast — either 20 mg twice a day or 30 mg twice a day — or placebo.

Apremilast induces significant improvement in both enthesitis and dactylitis through to week 104.

The placebo-controlled phase of the trials was 24 weeks, with an early escape option at 16 weeks. Double-blind treatment with apremilast continued to 52 weeks, and an open-label extension of the PALACE trials meant patients could continue to receive apremilast for up to 4 more years.

MASES was used to assess enthesitis at baseline, week 52, and week 104. The number of digits with dactylitis was also assessed.

Long-term improvement in enthesitis and dactylitis severity was seen in patients who received apremilast, Dr Gladman reported.

Table. PALACE Outcomes During the 104-Week Treatment Period

Outcome Apremilast 20 mg Apremilast 30 mg
   Mean baseline MASES 4.6 4.3
   Mean change in MASES from baseline, % –55.1 –57.5
   Patients achieving a MASES of 0, % 51.5 48.7
   Mean baseline count 3.2 3.4
   Mean change in count from baseline, % –75.8 –80.0
   Patients achieving count of 0, % 72.9 77.5


"Apremilast was well tolerated for up to 104 weeks, and any adverse events we did see were mostly mild," Dr Gladman explained.

The main adverse events were largely gastrointestinal in nature, such as diarrhea and nausea. "Importantly, most of the gastrointestinal events occurred within the first few weeks and resolved pretty quickly," she reported.

Laboratory abnormalities were generally infrequent and transient, and there were no cases of tuberculosis.

There is "actually very little evidence" that the DMARDs currently used to treat psoriatic arthritis, like methotrexate, "work particularly well for enthesitis and dactylitis," said Christopher Edwards, MD, from University Hospital Southampton in the United Kingdom. Dr Edwards presented results from PALACE 3, which evaluated the effect of apremilast on disease activity.

"Apremilast works as an anti-inflammatory because it blocks the signaling that causes proinflammatory cytokines to be produced," he told Medscape Medical News. And its intracellular effect "inhibits tumor necrosis factor and interleukin-17."

As PALACE 3 showed, the two twice-daily doses of apremilast led to clinically meaningful improvements in swollen and tender joints, physical function, and psoriasis for up to 104 weeks of treatment.

"We went through a process during which everybody convinced themselves that subcutaneous administration of psoriatic arthritis drugs was fine, so we did that for 10 years with other biologic therapies," Dr Edwards explained.

Oral Advantage

"Now, we've come back to saying, isn't it interesting that patients might prefer oral medications," Dr Edwards said. In addition, "you don't need to do any blood monitoring, as you do with methotrexate, and our safety experience so far with apremilast is very reassuring."

The fact that apremilast is an oral formulation is advantageous, said Laure Gossec, MD, from Université Pierre et Marie Curie and Pitié Salpêtrière Hospital in Paris.

"It is a useful addition to the therapeutic possibilities for psoriatic arthritis," she told Medscape Medical News. And this study "indicates that it has good efficacy in both enthesitis and dactylitis."

However, the three PALACE studies demonstrated that apremilast is only moderately effective for synovitis in joints and for psoriatic arthritis with skin involvement, she pointed out.

"The place of apremilast in the therapeutic algorithm for psoriatic arthritis remains to be determined," Dr Gossec said.

This study was sponsored by the Celgene Corporation. Dr Gladman reports receiving grant or research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer, Novartis, and UCB. Dr Edwards reports receiving grant and research support from or serving as a consultant for Celgene Corporation, Pfizer, Roche, and Samsung. Dr Gossec has disclosed no financial relationships relevant to the PALACE studies.

European League Against Rheumatism (EULAR) Congress 2015: Abstract OP0169, presented June 12, 2015; Abstract THU0416, presented June 11, 2015.


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